Special Collection in Memory of Prof.

Pedro Joseph-Nathan – Review

Natural Product Communications
Volume 18(7): 1–14
Anticancer Properties of Mexican Medicinal © The Author(s) 2023
Article reuse guidelines:
Plants: An Updated Review sagepub.com/journals-permissions
DOI: 10.1177/1934578X231187458
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Sofía Isabel Cuevas-Cianca1#, Rubí Esmeralda González-Campos2#,

Jorge Luis Mejía Méndez1#, Eugenio Sánchez Arreola1, Zaida Nelly Juárez3
and Luis Ricardo Hernández1

Abstract
Mexico is considered a mega-diverse country due to its terrestrial, marine, and biological richness. Throughout history, Mexican
medicinal plants have been used to elaborate decoctions, pastes, and powders to treat neoplastic, gastrointestinal, metabolic, neuro-
degenerative, skin, and infectious disorders. Cancer constitutes a group of diseases that result from the uncontrolled growth and
proliferation of cells. Current treatment regimens against it encompass the administration of chemotherapy, radiotherapy, targeted
therapy, and immunotherapy. Despite their possible efficacy, their use is often related to the possibility of relapse, the development of
serious adverse events, toxic effects, and many drug-resistance mechanisms. As an alternative, Mexican medicinal plants have been
extensively studied using their capacity to elicit strong anticancer activities and possess novel bioactive and safe compounds. This
review concentrates on the knowledge gained in recent years (2011–2022) about the anticancer properties of extracts and isolated
compounds from Mexican medicinal plants. Generalities, antioxidant activities, features of cancer cells, and drug-resistance mech-
anisms are reviewed in this work. In addition, the possible anticancer mechanisms of isolated compounds and the status of FDA-
approved cancer drugs derived from plants are covered. Finally, our perspective on the future of traditional medicine and Mexican
medicinal plants in cancer treatment is presented.

Keywords
traditional medicine, Mexican medicinal plants, nature products, bioactivities, cancer

Received: April 7th, 2023; Accepted: June 23rd, 2023.

Introduction However, the interest in medicinal plant research as a possi-

In the past, people used Mexican medicinal plants as healing,
religious, and magical resources to fulfill distinct purposes.1
Nevertheless, they are now exploited to discover modern ther-
apeutic agents and as a cost-effective alternative to treat, miti-
gate, or prevent numerous diseases.
Cancer comprises a group of diseases that result from the
uncontrolled growth and accelerated proliferation of cells.
Current treatment modalities against cancer encompass chemo-
therapy, radiotherapy, immune therapy, and targeted therapy
regimens. However, their poor bioavailability, low solubility,
and limited specificity manifest in severe, long-lasting, and
latent adverse events that can compromise patients’ prognosis
and well-being.2
Plants have a long history in cancer treatment, although they
have often been viewed with some skepticism due to the dis-
ease’s characteristics. Many people with cancer currently want
to undergo alternative therapies with products mainly of tradi-
tional use.3 Added to the above, the research results on the
activity against cancer of various plants confirm the importance
of expanding knowledge in this area.
ble source for obtaining active principles has a history; institu-
tions such as the Cancer Research Institute have been
developing research in this field since 1955.3
1
Department of Chemical Biological Sciences, Universidad de las Américas
Puebla, San Andrés Cholula, Puebla, Mexico
2
Biotechnology Faculty, Deanship of Biological Sciences, Universidad Popular
Autónoma del Estado de Puebla, Santiago, Puebla, Mexico
3
Chemistry Area, Deanship of Biological Sciences, Universidad Popular
Autónoma del Estado de Puebla, Santiago, Puebla, Mexico
#
Authors contributed equally.
Corresponding Authors:
Zaida Nelly Juárez, Chemistry Area, Deanship of Biological Sciences,
Universidad Popular Autónoma del Estado de Puebla, 21 Sur 1103 Barrio
Santiago, Puebla 72410, Mexico.
Email: zaidanelly.juarez@upaep.mx
Luis Ricardo Hernández, Department of Chemical Biological Sciences,
Universidad de las Américas Puebla, Ex Hacienda Sta., Catarina Mártir S/N,
San Andrés Cholula, Puebla 72810, Mexico.
Email: luisr.hernandez@udlap.mx

Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License
(https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission
provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).
2 Natural Product Communications
Therefore, the importance of concentrating the knowl-
edge of recent years on this subject becomes evident. In
this review, the anticancer activities of isolated compounds
and extracts prepared from Mexican medicinal plants are
considered, as are their antioxidant effects, as an essential
fact in regulating the redox system. SciFinder, PubMed,
Google Scholar, and Wiley Online Library databases were
used to update the knowledge about the anticancer proper-
ties of Mexican medicinal plants, considering papers pub-
lished from 2011 to 2022.
Medicinal Plants
Generalities
Mexico is one of the countries in America with one of the most
significant ancestral traditions and the richest in medicinal
plants, where just over 3000 species used in natural remedies
are registered. However, there is little research on the use and
management of medicinal plants; therefore, there is little ethno-
botanical information on this topic.4 The data that can be gath-
ered in the various parts of the nation would be relevant from
an ethnobotanical perspective.5
The use of medicinal plants is based on traditional knowl-
edge created, transmitted, and reinvented by indigenous
groups and Mexican peasants.6,7 These same authors assert
that this knowledge adapts to the shifting conditions of the
natural and social environments to meet the social need for
health care in the broadest range of environmental and social
circumstances.
Many novel compounds with anti-inflammatory, antiviral,
and several other biological activities have been discovered
due to scientific research on how plants are used in specific cul-
tural contexts. To protect against insect and microbial attacks
and adapt to harsh environments, plants develop a wide range
of bioactive substances and secondary metabolites (tempera-
ture, humidity, light intensity, drought, etc).8 Bioactive sub-
stances can have beneficial or adverse effects on people or
animals.9
The compounds responsible for the reported beneficial
effects are named natural products or secondary metabolites
all plants produce; they are not involved in vital processes but
have the purpose of defending them from adverse conditions
such as insects, parasites, herbivores, drought, and ultraviolet
light.10 For example, plants produce specialized morphological
structures, secondary metabolites, and proteins with toxic,
repellent, and/or antinutritional effects on the herbivores
to counter the herbivore attack.11 Among the best-known
secondary metabolites are alkaloids, terpenes, and phenolic
compounds.10
Secondary metabolites are substances formed from primary
metabolism that are only found in a particular taxonomic
group of plants and have a restricted distribution in the
plant kingdom.12 It was once believed that secondary com-
pounds were created with somewhat ambiguous purposes.
However, it has since been discovered that many of them
have significant yields and serve many purposes in plants.13
Further research has revealed that organisms have evolved
to produce these complex and often toxic chemicals for
defense, communication, and predation.14
Many reports have demonstrated nature’s continuing and
valuable contributions as a source not only of potential che-
motherapeutic agents but also of lead compounds that have
provided the basis and inspiration for the semisynthesis or
total synthesis of effective new drugs.15 Additionally, prom-
ising substances have been identified for cancer therapy,
including vincristine, paclitaxel, and etoposides, among
others.5
According to the WHO, a plant species is considered a
medicinal plant if it has compounds that can either be used ther-
apeutically or which can be used to synthesize new medica-
tions.16 Furthermore, according to the efficacy principle,
which states that what is observed to work is accepted and
adopted while the rest is abandoned, popular knowledge of
the biological activity of medicinal plants is based on efficacy.
However, a challenge with popular phytotherapy is the difficulty
in controlling the dosage and quality of the product, which can
result in risks and harm to health.16
Medicinal plants are a rich source of bioactive compounds
with beneficial properties; furthermore, they have contributed
much to modern Western medicine in different ways. For
example, pure compounds obtained from them are used
directly as medicines or as raw materials to produce new
medicines.10,17
Traditional medicine in Mexico has always utilized medicinal
plants. Depending on the situation or recipe at hand, several
plant components are used. The leaves and flowers are used
most frequently, with the stem or root rarely used. The con-
sumption of medicinal plants might take the form of direct
ingestion, infusions, or homeopathic presentations.18 Most of
the time, the active chemical principles underlying the positive
effects ascribed to them are unknown. Numerous research
teams have been working to pinpoint molecules having biolog-
ical activity in recent years to advance the knowledge in this
area. Many species used in traditional medicine have not all
been thoroughly chemically characterized.18 The whole or any
part of a medicinal plant can be used either alone or in combi-
nation, and the most common way they are administered is
through infusions.10
However, over the last quarter century, environmental and
cultural changes and the transition of economies from subsis-
tence to market-based have seriously impacted all aspects of tra-
ditional medical systems affecting traditional medicine’s
resource base and environment. Overharvesting medicinal
plants and animal species has resulted in resource degradation,
the loss of biodiversity, and the loss of indigenous medical
knowledge and traditions, leading to a breakdown of traditional
medical systems.19
On the other hand, ethnobotanical investigations have
allowed the discovery of critical new compounds with biological
Cuevas-Cianca et al.
activity, such as prostratin, which acts on the AIDS virus, and a
series of compounds with anti-inflammatory properties. In
addition, several authors have reported studies about endemic
plants considered medicinal or aromatic; they show a promising
future due to their compounds or biological activities.20 These
species are sold nationwide, but other compounds, like taxol,
are already being semisynthesized to be used in cancer treat-
ments worldwide.20
Humans have used medicinal plants for centuries to treat
their health problems. These resources contain helpful sub-
stances for therapeutic purposes or as precursors for new
drug synthesis,21 which contribute to recovering the popula-
tion’s health, considering that health is the state of complete
physical, mental, spiritual, emotional, and social well-being.17
Approximately 60% of drugs currently used for cancer treat-
ment have been isolated from natural products.22 In Mexico,
more than 90% of the general population uses medicinal
plants in common practice to empirically treat several dis-
eases.23 In urban areas, the populations refer to the local
healers, called “chamanes,” for medicinal plant prescriptions
to receive treatment.24
Mexican Medicinal Plants
Mexico is one of America’s countries with the most significant
ancestral tradition and assiduous medicinal herb user, with just
over 3000 registered species used in natural remedies. However,
there are few investigations on medicinal plants’ use and man-
agement. Therefore, because of the little ethnobotanical infor-
mation on this topic, more ethnobotanical studies are
required.4,5
Biodiversity refers to the various forms of life that can
develop in a country, such as plants, animals, and microorgan-
isms, and the genetic material that forms between them. Mexico
is a country of great biological wealth, diversity of ecosystems,
and genetic variability due to its topography and climatic varia-
tions.25 As a result, Mexico ranks 4th among the countries con-
sidered to have biological megadiversity and has about 10% of
all known species, with many being endemic.26
Mexico also has an ancient tradition of using medicinal
plants.27 It is considered, after China, the country with the
most significant number of registered medicinal plants. Eighty
percent of the Mexican population frequently uses herbalism;
however, only 5% of approximately 4500 species have been
pharmacologically analyzed.25 Of the 250 species commercial-
ized daily, more than 85% come from collections without sus-
tainable management plans.28
Different private and government institutions in Mexico
have conducted significant efforts to gather information on
medicinal plants. Nowadays, health institutions and the phar-
maceutical industry have started paying attention to studies
with scientific evidence that show that it is a valuable alternative
to solve health problems.20
The medicinal properties, knowledge, and applications of
plants have been maintained for millennia among indigenous
3
peoples. This knowledge is complemented by analyzing the
active principles investigated in the plants. However, to maintain
the benefits of indigenous and scientific knowledge, it is essen-
tial to carry out sustainable management of medicinal plants
and the ecosystems where they develop.29
According to compiled articles, several Mexican medicinal
plants’ anticancer activities have been reported from 2011 to
2022. For instance, it has been demonstrated that methanol
extracts from Justicia spicigera Schld can decrease the viability
of hepatocellular carcinoma cells. The anticancer effect exe-
cuted by these extracts was attributed to the presence of
widely known flavonoids such as kaempferol. On the other
hand, it has been unveiled in recent years that nonpolar solvents
such as dichloromethane can be useful to prepare extracts from
Aristolochia foetida Kunth capable of decreasing the cell viability
of breast cancer cells by altering their mitochondrial membrane
potential and inducing late apoptosis. Comparably, solvents
such as hexane have been used to extract bioactive components
from Distictis buccinatoria (DC.) A.H. Gentry that can reduce the
number of viable colon and nasopharyngeal carcinoma cells. In
addition, it is interesting to note that a combination of solvents
such as dichloromethane with methanol has been used to
prepare cytotoxic extracts from Linum scabrellum Planch.,
which can alter the cell cycle, disrupt tubulin polymerization,
and execute apoptotic effects among a variety of cancer cells
lines such as prostate, breast, colon, and cervical cell lines.
Given that carcinogenic events are related to redox reactions,
the antioxidant capacity of extracts from Veronica americana
Schwein. ex Benth. have been reported to perform a scavenging
activity of DPPH and ABTS radicals and exert cytotoxic effects
against prostate, larynx, and nasopharyngeal cancer cells. The
anticancer activities of other Mexican plants that have been
studied during 2011–2022 are summarized in Table 3.
Mechanism of Action of Drugs from Plants and
Mechanism of Resistance of Cancer Cells
Natural products can possess simple or complex chemical
structures derived from plants’ secondary metabolism.
Natural products’ structural arrangement and steric properties
are exploited in drug development and cancer treatment to
prepare effective and selective antineoplastic medicines that
interact with cancer cells and disrupt carcinogenic processes
through multiple mechanisms.
Natural products can generally act as modulators of cancer
cell signaling pathways, or as stimulators of adaptive and
innate immune responses.30 In addition, given their structural
diversity, they can also disrupt critical molecular and cellular
processes required for cancer cells’ survival, proliferation, pro-
gression, metabolism, and differentiation.31
Cancer is classified into 3 stages: the first one is initiation,
in which cellular DNA damage and mutation occur as a
result of carcinogen exposure and the failure of DNA repair
mechanisms; the second one is promotion, in which
4 Natural Product Communications
hyperproliferation, tissue remodeling, and inflammation occur
as a result of the expansion of initiated cells; and the third
one is progression, in which preneoplastic cells form tumors
through clonal expansion, which is aided further by an increase
in genomic instability and altered gene expression.32
Current treatment modalities against cancer are prone
to failure due to the capacity of cancer cells to develop
drug-resistance mechanisms, so different carcinogenesis stages
necessitate different chemotherapeutic approaches.
Drug-resistance mechanisms can be either disease-specific
or evolutionarily conserved. However, they are regularly catego-
rized into intrinsic and acquired.33
Intrinsic drug-resistance mechanisms arise from genetic
aberrations (eg, gene amplifications, deletions, or chromosomal
rearrangements) among genes involved in cancer cells’ growth,
proliferation, or death.34,35
Common mutated structures involved in this category are
the human epidermal growth factor receptor 2 (HER2),
microRNAs (eg, miRNA21), and drug transporters (eg,
BCRP and MRP1).36,37 The existence of such mutations can
limit the initial response to cancer therapy and promote
Figure 1. Drug-resistance mechanisms of cancer cells. Adapted from “Antibiotic Resistance Mechanisms” by BioRender.com (2022). Retrieved
from https://app.biorender.com/biorender-templates.
cancer relapse. On the contrary, acquired drug-resistance mech-
anisms are developed during treatment through preexisting
genetic aberrations, the secretion of growth factors, epigenetic
modifications, and metabolic adaptations.38 In Figure 1, the
drug-resistance mechanisms of cancer cells are depicted.
Nowadays, roughly half of the conventional chemotherapy
agents are derived from plants, with roughly 25% being directly
derived from plants and 25% being chemically modified ver-
sions of phytoproducts.39 Table 1 describes the mechanisms
of action against cancer of the major groups of compounds
found in plants approved by the FDA. Table 2 shows alkaloids,
flavonoids, and terpenes derived from Mexican medicinal plants
with cytotoxic activity against various cancer cell lines.
Compounds belonging to some groups are expected to act
the same way as other group members. As a result, alkaloids
are likely to act via binding with tubulin, affecting microtubule
activity40-42 and reducing protein synthesis.43,44 Flavonoids act
as protein-kinase inhibitors, topoisomerase inhibitors, poisons,
antiangiogenic agents, and antioxidants; terpenes are predicted
to suppress inflammatory reactions, limit metastasis, and
induce apoptosis.45‐49
Cuevas-Cianca et al. 5

Table 1. Compound Groups With Mechanisms of Action, Food and Drug Administration (FDA)-Approved Compounds, and Cancer Types for
Which They are Indicated.50
Group of
compounds Mechanism of action FDA-approved Structure Type of cancer
43
Vinca alkaloids Interactions with tubulin Vinorelbine tartrate 1 Nonsmall cell lung cancer
and disruption of (1994)
microtubule Vindesine (clinical trials) 2 Lung cancer (Phase III), small cell lung carcinoma
function40-43,51-53 (Phase II), Hodgkin lymphoma (Phase II), central
nervous system lymphoma (Phase II), and diffuse
large B-cell lymphoma (Phase II)
Vincristine sulfate (1963) 3 Acute leukemia, Hodgkin lymphoma, neuroblastoma,
non-Hodgkin lymphoma, rhabdomyosarcoma, and
Wilms tumor
Vinblastine sulfate (1965) 4 Breast cancer, choriocarcinoma, Hodgkin lymphoma,
Kaposi sarcoma, mycosis fungoides, non-Hodgkin
lymphoma, and testicular germ cell tumors
Taxanes44 Paclitaxel (1992) 5 AIDS-related Kaposi sarcoma, breast cancer,
nonsmall cell lung cancer, and ovarian cancer
Docetaxel (1996) 6 Breast cancer, nonsmall cell lung cancer, prostate
cancer, squamous cell carcinoma of the head and
neck, and stomach adenocarcinoma
Cabazitaxel (2010) 7 Prostate cancer
Camptothecin Inhibiting human DNA Irinotecan hydrochloride 8 Colorectal cancer
derivatives topoisomerase I44,54,55 (1996)
Topotecan (1996) 9 Cervical cancer, ovarian cancer, and small cell lung
cancer
Cephalotaxus Inhibiting protein Omacetaxine 10 Chronic myelogenous leukemia
alkaloids synthesis43,44,56 mepesuccinate (2012)
Flavonoids43 Protein-kinase inhibitors, Genistein (clinical trials) 11 Breast cancer (Phase II), prostate cancer (Phase II),
topoisomerase inhibitors, colorectal cancer (Phase I/II), nonsmall cell lung
poisons, antiangiogenic cancer (Phase II), pancreatic cancer (Phase II),
agents, and antioxidants; bladder cancer (Phase II), kidney cancer and
modulate cell multidrug melanoma (Phase I), endometrial cancer (Phase I),
resistance mediated by and cancer of head and neck (Phase I)
Pgp45-49 S-equol (clinical trials) 12 Breast cancer (Phase I)
Isoquercetin (clinical 13 Renal cell carcinoma and Kidney cancer (Phase II)
trials)
Idronoxil (clinical trials) 14 Prostate cancer (Phase II), Fallopian tube cancer,
ovarian cancer, primary peritoneal cavity cancer
(Phase I/II), and adult solid tumor (Phase I)
Sesquiterpene Inhibition of inflammatory Artemisinin (clinical trials) 15 Breast cancer (Phase I)
lactones43 responses, prevention of Artesunate (clinical trials) 16 Colorectal cancer and bowel cancer (Phase II), breast
metastasis, and induction cancer (Phase I), solid tumors (Phase I), cervical
of apoptosis57-63 intraepithelial neoplasia (Phase I), and
hepatocellular carcinoma (Phase I)
Artemether (clinical trials) 17 Solid tumors (Phase II)

Discussion In Mexico, cancer is the second leading cause of death, since

During the last few decades, cancer has constituted a significant
human health concern regarding its incidence and mortality.
According to the World Health Organization (WHO), it has
been estimated that cancer is the leading cause of death world-
wide for men and women.73 Even though, the incidence of
cancer among both populations can vary according to factors
associated with sociodemographic and geographic factors.74 It
has been recently reviewed that most cancer deaths are esti-
mated to occur in Asian, European, and American countries.75
it has been responsible for 12.8% (approximately) of deaths
over the last decade.76 Among men, various types of cancer
have exhibited the highest mortality rates; some of these sub-
types include lung, gastric, and prostate cancer.77 In contrast,
cervical and breast cancer are the most frequently diagnosed
among women younger than 50 years old.76,78
Given the limitations of current treatment modalities against
cancer, traditional medicine and its derivatives (eg, aromather-
apy and acupuncture) are considered an alternative to disrupt
key carcinogenic phenomena such as angiogenesis, metastasis,
6 Natural Product Communications

Table 2. Compounds Isolated From Mexican Medicinal Plants With Anticancer Activity.64
Type of
compound Plant Name of the compound ED50 [µg/mL] (cell line) Ref.
65
Alkaloids Tecoma stans (L.) Juss. ex 5-Hydroxy skytanthine hydrochloride (18) N/A(MCF-7)
Kunth
66
Hippocratea excelsa Hippocrateine I (19) 0.185 (9PS)
Kunth
Flavonoids Polanisia dodecandra (L.) 5,4′ -Dihydroxy-3,6,7,8,3′ -pentamethoxyflavone (20) 0.98 (TE-671) 67

DC. 5,3′ -dihydroxy-3,6,7,8,4′ -pentamethoxyflavone (21) 0.045 (KB), 0.6 (A-459), 4.4 (HCT-8),
0.055 (P-388), 0.55 (RPMI-7591), and
0.069 (TE-671)
68
Eysenhardtia polystachya (3S)-7-Hydroxy-2,3,4,5,8-pentamethoxyisoflavan 3.8 (KB)
(Ortega) Sarg. (22)
Isoduartin (23) 2.63 (KB)
69
Lippia graveolens Kunth Galangin (24) 9.9 (U-251) and 10.13 (SK-LU-1)
70
Terpenes Viguiera quinqueradiata Budlein A (25) 1 (KB) and 1 (P-388)
(Cav.) A. Gray
71
Iostephane heterophylla Trachylobanoic acid (26) 1 (UISO-SQC-1)
(Cav.) Benth. ex Hemsl.
72
Smallanthus maculatus Ursolic acid (27) 3.7 (HCT-15), 3.4 (UISO-SQC-1), and
(Cav.) H. Rob 3.6 (OVCAR-5)
Abbreviations: MCF-7, breast adenocarcinoma; 9PS, murine lymphocytic leukemia; TE-671, rhabdomyosarcoma; KB, nasopharyngeal carcinoma; A549, lung
carcinoma; HCT-8, ileocecal carcinoma; P-388, murine leukemia cell line; RPMI-7591, melanoma; U-251, human glioma; SK-LU-1, lung adenocarcinoma;
UISO-SQC-1, squamous cervix carcinoma; HCT-15, colorectal adenocarcinoma; OVCAR-5, ovary carcinoma.

and proliferation.79 However, various factors can dictate the
effectiveness of this approach, for example, the stage of
disease, type of cancer, disease duration, and bioactivity of
medicinal plants.80
It is estimated that more than 90% of Mexicans use prepa-
rations based on medicinal plants due to the ancestral knowl-
edge developed through time.81 As compiled in Table 3,
Mexican medicinal plants can decrease the viability of breast,
lung, colorectal, oropharyngeal, and hepatocellular cancer cell
lines by fragmenting DNA, enhancing the generation of ROS,
promoting apoptosis, upregulating or downregulating gene
expression, interfering with cell cycle phases, and inducing mor-
phological changes. Interestingly, we identified that in multiple
reports, these events are predominantly promoted in vitro or
in vivo with extracts prepared with mildly polar to polar solvents
such as ethyl acetate and ethanol.
Many plants show selective activity, such as Justicia spicigera,
which is highly cytotoxic against the HEP-G2 (liver) and
HeLa (cervix) cell lines with IC50 values of 2.92 and 17 µg/
mL, respectively; however, for other cell lines, its IC50 is
>23 µg/mL.82-84 Rhus trilobata has activity against the Caco-2
(colon) cell line (IC50 5 µg/mL).85 On the other hand,
Veronica americana methanol extract has an IC50 as low as
0.169 µg/mL against the HF-6 (colon) cell line.86 In addition,
some of the reported medicinal plants’ anticancer activity can
be influenced by their origin and harvest month. For
example, a study of the antitumor activity of Annona muricata
evaluated the activity of its leaves collected from Acapulco
and Tecpan in Guerrero state, Mexico in different months
throughout a year. The results showed greater activity of the
leaves collected in December from both locations; however,
the sample collected in Acapulco showed an ED50 of
10.8 mg/kg, lower than that of doxorubicin (15.57 mg/kg), a
drug used to treat different cancer types and used in this
study as the positive control.87 Unfortunately, comparisons
between plants are difficult because results are given in different
terms, such as IC50, ED50, CC50, and so on; Table 3 summa-
rizes these values for different plants and cell lines.
In pathophysiological events, the exacerbated generation of
ROS is commonly related to a series of diseases. As with
other sources, Mexican medicinal plants also contain a variety
of secondary metabolites that can act as antioxidants, which
are necessary to prevent the generation of free radicals and
retain or prevent the progression of cancer. As presented in
Table 3, extracts from Veronica americana can exert antioxidant
activity by reducing the formation of radicals such as ABTS
and DPPH. This is important since it demonstrates that
Mexican medicinal plants can display convenient biological
activities for treating cancer.
As previously mentioned, bioactive secondary metabolites can
be extracted with solvents from different polarities using distinct
techniques. Polar solvents (eg, methanol, ethanol, or water) or
their mixtures are convenient for studying the therapeutic proper-
ties of natural compounds as they can extract the highest number
of bioactive compounds. For example, polar extracts are conve-
nient for cancer treatment, as they contain numerous secondary
metabolites that execute strong cytotoxic and antioxidant effects
on cancer cells.88 Some of these compounds are flavonoids,
such as quercetin, kaempferol, and hesperidin, and polyphenols,
such as coumaric acid and caffeic acid.89
Table 3. Anticancer Effects of Mexican Medicinal Plants.
Family Species Region Part used Anticancer effect Reference
82
Acanthaceae Justicia spicigera Schltdl. N.I. Leaves • Methanol extract reduced the viability of human hepatocellular carcinoma cells.
• Methanol extract also exhibited antihemolytic activities.
• The observed effects can be attributed to kaempferitrin or kaempferol among extracts.
• The IC50 value calculated for this species was 2.92 μg/mL against the HEP-G2 cell line.
Cuevas-Cianca et al.

83
Acanthaceae Justicia spicigera Schltdl. San Luis Leaves • Treatment with ethanol extracts decreased the viability of human breast carcinoma and
Potosí cervical cancer cells.
• The anticancer activities can be attributed to flavonoids and tannins.
• Against the MCF-7 breast cancer cell line, the IC50 value calculated was 48 μg/mL.
• Against HeLa, SKOV-3, SW-480, and DU-145 cell lines, the IC50 were 17, 43, 49, and
>200 μg/mL, respectively.
84
Acanthaceae Justicia spicigera Schltdl. Veracruz Leaves and stems • Treatment with hydroalcoholic extract produced cytostatic effects against prostate cancer
cells.
• Treatment with hydroalcoholic extract arrested the cell cycle of prostate cancer cells at the G0
phase and interphase.
• Against the tested cell line (LNCaP), the IC50 value calculated was 3026 μg/mL.

85
Anacardiaceae Rhus trilobata Nutt. Chihuahua Stems • Treatment with aqueous extract decreased the viability of ovarian epithelium, colorectal
adenocarcinoma, and lung epithelium cells.
• Treatment with aqueous extract induced morphological changes among the tested cell lines.
• Treatment with extracts did not induce adverse toxicological effects in female BALB/c mice.
• The recorded effects can be due to quercetin, gallic acid, quercetin, or ethyl gallate.
• Against the Caco-2 cell line, the IC50 for aqueous extract was 5 μg/mL.

87
Annonaceae Annona muricata Linn. Guerrero Leaves • Obtained ethanol extracts inhibited tumor growth on BALB/c mice inoculated with breast
cancer cells.
• The toxicity of ethanol extracts was tested in brine shrimp and mice models.
• The anticancer activity of extracts can be due to narcissin, nicotiflorin, and rutin.
• Against the 4T1 cell line, the CC50 values calculated for the obtained extracts ranged from
75.9 to 139.1 μg/mL.
93
Apiaceae Eryngium carlinae Jalisco Aerial parts • Treatment with the methanol extract from this species decreased the viability of colon cancer
F. Delaroche. cells.
• The reported biological activity can be due to flavonoids, saponins, and triterpenoids.
• The methanol extract CC50 against the Caco-2 cell line was 356 μg/mL.

94
Aristolochiaceae Aristolochia brevipes Baja N.I. • Treatment with ethanol extract was highly cytotoxic against human colorectal cancer cells.
Benth. California • The registered effect can be attributed to the presence of cardiac glycosides.
Sur • The IC50 against the HCT-116 cell line was 1.0 μg/mL.

95
Aristolochiaceae Aristolochia foetida Kunth Michoacán Leaves and stems • The dichloromethane extract was cytotoxic against human breast cancer cell lines.
• Dichloromethane extracts decreased the mitochondrial membrane potential and induced late
apoptosis in the tested cancer cell line.

(Continued)
7
 8
Table 3. Continued.
Family Species Region Part used Anticancer effect Reference
• The observed anticancer effect can be due to hexadecenoic acid, methyl hexadecanoate, or
ethyl hexadecanoate.
• The stems and leaves dichloromethane extracts showed IC50 of 45.9 and 47.3 μg/mL,
respectively, against the MCF-7 cell line.
94
Asclepiadaceae Asclepias subulata Decne. Baja N.I. • The ethanol extract from this species resulted in a high cytotoxic effect against human
California colorectal cancer cells, which can be due to the presence of cardiac glycosides.
Sur • The IC50 against the HCT-116 cell line was 0.4 μg/mL.

93
Asteraceae Cirsium mexicanum DC. Jalisco Flowers • The methanol extract was poorly cytotoxic against colon cancer cells.
• The registered effect can be attributed to terpenoids, tannins, and saponins.
• For flowers and whole plants, the CC50 were 250 and 323 μg/mL, respectively.

96,97
Bignoniaceae Distictis buccinatoria Morelos Aerial parts • The hexane and dichloromethane extracts exhibited cytotoxic effects against colon and
(DC.) A.H. Gentry nasopharyngeal carcinoma cell lines.
• Anticancer effects can be due to the presence of herniarin and daphnoretin.
• Against KB and HCT-15 cell lines, the ED50 values ranged from 8.3 to >20 μg/mL.

98
Burseraceae Bursera copallifera (DC.) Guerrero Leaves • Methanol extracts were cytotoxic against breast cancer cell lines.
Bullock • The anticancer activity can be due to hydroxycinnamic acid and derivatives of well-known
flavonoids such as quercetin.
• The IC50 values calculated were 34.88 and 12.43 μg/mL for MCF-7 and MDA-MB-231 cell
lines, respectively.
99
Celastraceae Semialarium mexicanum N.I. Root bark • Among the obtained extracts, the light petroleum extract was cytotoxic against tumorigenic
(Miers) Mennega and nontumorigenic breast cancer cells.
• The light petroleum extract induced apoptosis of the tested cell lines by inducing oxidative
stress.
• The IC50 ranged from 3.35 to 15.55 μg/mL against MDA-MB-231, MCF-10A, MCF-7, and
PBMCs cell lines.
93
Chenopodiaceae Chenopodium ambrosioides Jalisco Leaves • Treatment with methanol extract exerted a low cytotoxic effect against colon cancer cells.
L. • The observed activity can be due to ascaridole or its derivatives.
• The CC50 value calculated for the fruit (seed) methanolic extract was 45 μg/mL against the
Caco-2 cell line.
100
Convolvulaceae Ipomoea thyrianthina Puebla Roots • Methanol extract was cytotoxic against human epithelial carcinoma cells.
Lindl. • The anticancer activity of the extract can be attributed to acylated tetrasaccharides.
• The identified compounds exhibited cytotoxicity against the KB cell line with ED50 values
that ranged from 2.5 to 2.8 μg/mL.
101
Crasssulaceae Kalanchoe flammea Stapf Tabasco Leaves • The anticancer properties of ethyl acetate extract were related to their capacity to induce the
generation of ROS, promoting the release of cytochrome C, producing the translocation of
phosphatidylserine, activating caspase 3 and 9, arresting the cell cycle, causing DNA
fragmentation, and downregulating the expression of proteins related to apoptosis.
• Treatment with ethyl acetate extract reduced the viability of prostate cancer cell lines PC-3,
LNCaP, and PrEC (IC50 = 1.36, 2.06, and 127.05 μg/mL, respectively).
Natural Product Communications

(Continued)
 Cuevas-Cianca et al.

Table 3. Continued.
Family Species Region Part used Anticancer effect Reference
• The fraction rich in coumaric acid and palmitic acid demonstrated cytotoxic activity against
PC-3 cells (IC50 = 1.05 μg/mL)
102
Euphorbiaceae Cnidoscolus multilobus Veracruz Leaves • Treatment with ethanol–water extract inhibited the proliferation of the human cervical
(Pax) I.M. Johnst. cancer cell line (HeLa).
• Treatment with the obtained extract did not induce morphological changes.
• After 24 h exposure to treatment, the calculated IC50 value was 159.12 μg/mL.
• After 48 h exposure to treatment, the calculated IC50 value was 129.37 μg/mL.

Linaceae Linum scabrellum Planch.
Plantaginaceae Veronica americana
Schwein. ex Benth.
92
Querétaro Flowers, leaves, • Dichloromethane-methanol extract was cytotoxic against breast, colon, cervical, and prostate
stems, and cancer cell lines.
roots • 6-Methoxypodophyllotoxin (28) was responsible for the cytotoxic activity exhibiting an IC50
value range of 0.063 to 2.74 µg/mL against HF-6, MCF-7, PC-3, and SiHa, as well as toward
the normal fibroblasts line HFS-30.
• In the prostate PC-3 cancer cell line, 6-methoxypodophyllotoxin arrests their cell cycle at the
G2/M, disrupts tubulin polymerization, and exerts an apoptotic effect in a dose-dependent
manner.
• The IC50 values calculated for the CH2Cl2:MeOH extract ranged from 0.57 to 1.60 μg/mL
against the tested cell lines.
86
Morelos Flowers, leaves, • The obtained extract was cytotoxic against the cervix, breast, prostate, colon, larynx, and
stems, and nasopharyngeal cancer cells.
roots • Treatment with extract also exhibited scavenging activity of ABTS and DPPH radicals in a
dose-dependent manner.
• The exerted bioactivities can be due to the high phenolic content of this species.
• Against KB, HEp-2, HF-6, MCF-7, PC-3, and Ca Ski cancer cell lines, the IC50 values
calculated ranged from 0.169 to >20 μg/mL.

Abbreviations: IC50, half maximal inhibitory concentration; CC50, half cytotoxic concentration; ED50, half effective dose; ABTS, (2,2′ -azino-bis (3-ethylbenzothiazoline-6-sulfonic acid); DPPH, (2,2-diphenyl-1-picryl-hydrazyl-
hydrate); ROS, reactive oxygen species.
9
10 Natural Product Communications

It is well-known that several factors, such as water availability, studies are needed to assess the therapeutic potential of prepara-
humidity, minerals supply, light intensity, and temperature, can tions or isolated compounds from Mexican medicinal plants in
influence medicinal plants’ secondary metabolites production.8 clinical studies. In addition, there is an urgent need to propose
Given Mexico’s ecological and geographical richness, it is possible models to evaluate the toxicity of these sources.
to find medicinal plants distributed in all states. Here, we review The Mexican flora has been a source of medicinal products for
several studies where medicinal plants with anticancer properties millennia, and during the last century, many plants with activity
have been reported mainly in humid areas such as Yucatán, against cancer have been investigated. Mexico’s natural resources
Guerrero, Jalisco, and Veracruz (see Table 3). Also, following will continue to be an important source of new drugs.
other reports, Mexican plants can treat infections caused by path-
ogenic microorganisms such as Mycobacterium tuberculosis,
Staphylococcus aureus, and Escherichia coli.90
As represented in Table 1, secondary metabolites’ structural
diversity and superior bioactivity have enabled their translation
into clinical trials to treat lung, breast, ovarian, and colorectal
cancer in their distinct stages. Even though the evidence
about the translation of isolated compounds from Mexican
medicinal plants is limited, it has been recently reported that
acacetin, a flavone isolated from Agastache mexicana subsp.
Xolocotziana, is a promising analgesic and anti-inflammatory
molecule tested in preclinical trials.91 Comparably, aqueous
extracts from Galphimia glauca have exhibited significant anxio-
lytic activities in clinical trials.91
A few compounds isolated from Mexican plants were studied
for their cytotoxic activity against cancer cell lines. Table 2 shows
the ED50 of the different types of compounds found in Mexican
medicinal plants against cancer cell lines; these values range
between 0.04 and 10.13 µg/mL, where 5,3′ -dihydroxy-
3,6,7,8,4′ -pentamethoxyflavone (21) has the lowest ED50
against the cell line KB of nasopharyngeal carcinoma.67
6-Methoxypodophyllotoxin (28), isolated from Linum scabrellum,
deserves a special mention because it has an IC50 value range as
low as 0.063 to 2.74 µg/mL against HF-6 (colon), MCF-7
(breast), PC-3 (prostate), and SiHa (cervix), as well as toward
the normal fibroblasts line HFS-30, showing a high unspecific
activity.92

Conclusion
Mexican medicinal plants and their preparations are used to
treat and prevent cancer. The anticancer activity of Mexican
medicinal plants is attributed to their phytoconstituents and
capacity to interfere with major carcinogenic processes.
Against cancer in vitro or in vivo models, polar extracts from
Mexican medicinal plants exert potent anticancer and antioxi-
dant properties through the presence of recognized bioactive
secondary metabolites. Several studies have focused on the
activity of some of these plants against breast and prostate
cancer, which can be attributed to their incidence in
middle-income countries such as Mexico.
Several compounds isolated from medicinal plants are currently
under clinical or preclinical trials. However, for Mexican medicinal
plants, this evidence is limited. On the other hand, these medicinal
plants exhibit significant antimicrobial properties against patho-
genic bacteria, which is vital since cancer patients are prone to
develop pneumonia, tuberculosis, or sepsis. Therefore, further
Cuevas-Cianca et al.
Acknowledgements
J.L. Mejía-Méndez and S.I. Cuevas-Cianca thank Consejo Nacional de
Ciencia y Tecnología (CONACyT) for their doctoral fellowship. R.E.
González-Campos thanks CONACyT for her master’s fellowship.
Figure 1 was created using BioRender.com.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to
the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, author-
ship, and/or publication of this article.
ORCID iD
Luis Ricardo Hernández https://orcid.org/0000-0002-3877-1244
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