Seminars in Cancer Biology 40–41 (2016) 1–3

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Seminars in Cancer Biology

journal homepage: www.elsevier.com/locate/semcancer

Editorial

Bioactive natural products in cancer prevention and therapy: Progress

and promise

a r t i c l e i n f o a b s t r a c t

Keywords: Natural products represent a rich source for the discovery and development of cancer preventive and
Natural agents anticancer drugs. Nearly, 80% of all drugs approved by the United States Food and Drug Administration
Phytochemicals during the last three decades for cancer therapy are either natural products per se or are based thereon, or
Dietary
mimicked natural products in one form or another. With the advent and refinement of new technologies,
Cancer
such as genetic techniques for production of secondary plant metabolites, combinatorial synthesis and
Prevention
Therapy high-throughput screening, it is expected that novel compounds from natural sources, including medic-
inal plants, would be identified and developed as safe and effective chemopreventive and anticancer
drugs. Numerous bioactive natural compounds have been shown to be useful in prevention and therapy
of cancer by targeting various signaling molecules and pathways. Extensive literature underscores the
anticancer and chemopreventive activity of a plethora of naturally occurring agents, including phyto-
chemicals. Several of these molecules have been tested in clinical trials and some of them have shown
promise in combination therapy when administered along with standard chemotherapeutic agents. Thus,
accelerated chemopreventive and chemotherapeutic drug development from natural sources is of great
importance. In this special theme issue, contributions from eminent scientists and scholars around the
world presented critical analysis of the current progress and promise of natural bioactive constituents in
cancer prevention and therapy.
© 2016 Elsevier Ltd. All rights reserved.

Natural products, obtained from various sources have been
used for the prevention and treatment of various chronic ailments
since several centuries. Cancer still remains a dreaded disease
and the use of natural agents has shown significant therapeutic
efficacy against malignancies. Chemotherapeutic agents currently
used include taxol, obtained from the Pacific yew (Taxus brevifolia)
as well as vincristine and vinblastine, present in the Madagascar
periwinkle (Vinca rosea). Chemoprevention by consumption of phy-
toconstituents of dietary origin has been employed as an important
approach in the fight against cancer and has yielded promising out-
comes. It has indeed given us great pleasure, at the invitation of
Dr. Theresa Vincent, Editor, Seminars in Cancer Biology, to invite
reputed scientists all over the world to contribute to this spe-
cial issue titled “Bioactive natural products in cancer prevention
and therapy: Progress and promise”. In this journal issue, various
investigators active in the field of cancer research from all over
the world have contributed several interesting articles highlight-
ing the cutting-edge research on potential of natural products in
cancer prevention and therapy.
The first article by Dr. Marc Diederich’s group discussed the
role of diverse natural compound-induced non-canonical cell death
pathways, such as paraptosis, mitotic catastrophe, necroptosis,
anoikis, ferroptosis and methuosis. They also elegantly highlighted
the possible immune stimulatory potential of these non-canonical
forms of cell death that may offer therapeutic benefit to cancer
patients [1].
Various oncogenic transcription factors lead to an accelerated
production of cellular adhesion molecules, inflammatory cytokines,
chemokines, anti-apoptotic molecules and inducible nitric oxide
synthase during cancer promotion and progression. Dr. Gautam
Sethi and colleagues critically analyzed the existing literature on
the modulation of transcription factors by various bioactive natu-
ral compounds and suggested new directions for accelerating the
discovery of novel drug candidates derived from Mother Nature [2].
The next article by Dr. Govinda Rao Duddukuri and cowork-
ers evaluated the role of various natural products in the negative
regulation of arachidonic acid (AA) pathway that plays an impor-
tant role in tumor initiation and progression. These investigators
also discussed the pharmacodynamic/pharmacokinetic properties
of various AA inhibitors as well as highlighted the status of ongoing
clinical trials with these agents [3].
Although the impact of dietary phytochemicals on gene expres-
sion and signaling pathways have been extensively studied in
cancer, the role of dietary components on mammalian epigenome
is rapidly emerging. The review from Dr. Sanjay Gupta’s group
presented the role of various epigenetic mechanisms in the regula-
tion and maintenance of mammalian genome and highlighted the

http://dx.doi.org/10.1016/j.semcancer.2016.08.006
1044-579X/© 2016 Elsevier Ltd. All rights reserved.
2 Editorial / Seminars in Cancer Biology 40–41 (2016) 1–3
influence of dietary phytochemicals as epigenetic modifiers in can-
cer prevention and treatment [4].
Due to its tremendous therapeutic potential, neem (Azadirachta
indica L.) is referred to as “the wonder tree” or “nature’s drug store”
or “village pharmacy”. Dr. Anupam Bishayee and colleagues crit-
ically analyzed available laboratory and clinical studies on neem
and cancer. A salient feature of this work entails in-depth analysis of
molecular targets of neem phytochemicals to understand the trans-
lational impact of neem-derived products in cancer prevention and
therapy [5].
Bitter melon (Momordica charantia) has gained an enormous
attention in recent years as an alternative medicine due to its poten-
tial to target type II diabetes and obesity which are well known risk
factors for cancer. The review written by Dr. Rajesh Agarwal’s group
presented current knowledge on cancer preventive and therapeutic
attributes of bitter melon constituents [6].
Dr. Hasan Mukhtar and colleagues discussed up-to-date and key
findings on anticancer effects of fisetin, a flavonol present in fruits
and vegetables, such as strawberries, apple, cucumber, persimmon,
grape and onion. The underlying molecular mechanisms and future
directions of research to facilitate clinical development of fisetin
as a potent cancer chemopreventive/chemotherapeutic agent have
also been presented [7].
Dr. Young-Joon Surh and coworkers comprehensively sum-
marized the anti-inflammatory and pro-resolving properties of
docosahexaenoic acid (DHA) and its metabolites in relation to can-
cer chemopreventive potential with special focus on their effects in
regulation of different signal transduction cascades. They also pro-
vided a comprehensive overview of the safety and pharmacokinetic
profiles that can facilitate rapid development of clinically relevant,
stable synthetic analogues of DHA and its metabolites [8].
The next article by Dr. Bal Lokeshwar and coworkers highlighted
the importance of various natural compounds both for the preven-
tion and therapy of prostate cancer, a hormonally-driven cancer
which ranks first in incidence and second in cancer-associated mor-
tality in men in most industrialized countries of the West. These
natural substances have been found to modulate multiple onco-
genic targets involved in initiation, promotion and progression of
prostate cancer [9].
Breast cancer is one of the most common cancers diagnosed
among women and extended exposure to estrogen is associated
with an increased risk of this cancer. Many natural products and
bioactive compounds found in foods have been shown to inhibit
mammary carcinogenesis via inhibition of estrogen-induced oxida-
tive stress as well as estrogen receptor (ER) signaling. The review
by Dr. Nanjoo Suh’s group summarized the role of bioactive natural
products involved in the prevention and treatment of estrogen-
related and ER-positive breast cancer [10].
Dr. Shrikant Anant’s and co-researchers elegantly analyzed the
potential role of various important phytochemicals, including cur-
cumin, resveratrol, tea polyphenols (epigallocatechin-3-gallate and
epigallocatechin), sulforaphane, genistein, indole-3-carbinol, 3,3 -
diindolylmethane, vitamin E, retinoic acid, quercetin, parthenolide,
triptolide, 6-shogaol, pterostilbene, isoliquiritigenin, celastrol and
koenimbin that can be exploited to target breast cancer stem cells
to control the metastasis of this dreaded malignancy [11].
Dr. Dona Sinha and colleagues highlighted the critical role
of resveratrol (3,5,4-trihydroxy-trans-stilbene), a non-flavonoid
polyphenol present in several dietary sources, including grapes,
berries, soy beans, pomegranate and peanuts, in both breast cancer
prevention and therapy. They not only analyzed the diverse molec-
ular targets modulated by resveratrol and its various analogues, but
also provided evidence of their role in stem cell therapy as well as
adjuvant treatment of mammary carcinoma [12].
Dr. Rita Ghosh and co-investigators examined various molecu-
lar mechanisms affected by naturally occurring substances focusing
primarily on prostate cancer and deliberated on the disparate
results obtained from cell culture, preclinical and clinical studies
in an effort to highlight the use of whole extracts and isolated
constituents for cancer prevention and intervention. As discussed
by the authors, a lack of parallel comparison studies between the
whole natural products and their isolated compounds limits deci-
sive conclusions regarding the superior utility of one over the other
[13].
Finally, we hope that this special issue containing articles con-
tributed by our esteemed colleagues and world experts embodies a
serious effort in our understanding of full potential of natural prod-
ucts in cancer. We believe that these contributions provide both
resources and inspiration to readers and future investigators that
natural bioactive constituents may be a winning strategy to fight
against cancer.
Conflicts of interest statement
The authors declare no conflicts of interest.
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 Editorial / Seminars in Cancer Biology 40–41 (2016) 1–3 3

Anupam Bishayee (PhD) ∗ ∗ Corresponding author.

Department of Pharmaceutical Sciences, College of
∗∗ Corresponding author.
Pharmacy, Larkin Health Sciences Institute, 18301 N.
Miami Avenue, Miami, FL 33169, USA E-mail addresses: abishayee@ULarkin.org,
abishayee@gmail.com (A. Bishayee),
Gautam Sethi (PhD) ∗∗
phcgs@nus.edu.sg (G. Sethi).
Department of Pharmacology, Yong Loo Lin School of
Medicine, National University of Singapore, Singapore
Available online 23 August 2016
117600, Singapore