CHAPTER ONE

INTRODUCTION

1.0 introduction

1.1 Cancer
Cancer is a large group of diseases that can start in almost any organ or tissue of the body when
abnormal cells grow uncontrollably, go beyond their usual boundaries to invade adjoining parts
of the body and/or spread to other organs. The latter process is called metastasizing and is a
major cause of death from cancer. A neoplasm and malignant tumour are other common names
for cancer.
Cancer is the second leading cause of death globally, accounting for an estimated 9.6 million
deaths, or 1 in 6 deaths, in 2018. Lung, prostate, colorectal, stomach and liver cancer are the
most common types of cancer in men, while breast, colorectal, lung, cervical and thyroid cancer
are the most common among women.(WHO,2020)
The cancer burden continues to grow globally, exerting tremendous physical, emotional and
financial strain on individuals, families, communities and health systems. Many health systems in
low- and middle-income countries are least prepared to manage this burden, and large numbers
of cancer patients globally do not have access to timely quality diagnosis and treatment. In
countries where health systems are strong, survival rates of many types of cancers are improving
thanks to accessible early detection, quality treatment and survivorship care.(WHO,2020) . In
Nigeria, an estimated 72,000 cancer deaths occur annually, and 102,000 new cases are diagnosed
from its population of 200 million people. These are, however, estimates, it is necessary to
document the yearly trends and patterns of cancer mortality with regards to the different regions
in the country.(NCBI,2020)
The utilization of medicinal plants in the treatment of cancer has its roots in ethnoveterinary
medicine. While the majority of evidence regarding the anticancer properties of these plants
used to be anecdotal and lacked scientific validity, there is now a growing body of controlled
experimental studies aiming to validate and quantify their efficacy. Numerous plants have indeed
demonstrated anti cancer activity in controlled experiments, either through direct ingestion of
the entire plant or administration of plant extracts to patients with cancer of low risk and high
risk .(Anthanasiadou et al 2007)
A. sativum L., from family amaryllidaceae also known as garlic, is one of the medicinal plants
under study for its anticancer activity and is a rich source of S-allylcysteine and S-allylmercapto-L-
cysteine. These bioactive compounds are known to exhibit high radical scavenging activity, which
is essential in the inhibition of cancer development. S-allylcysteine also retarded tumor growth
[24]. Additionally, A. sativum repressed the proliferations of skin, colon, lung, prostate, leukemia,
and breast cancer cells in vitro and should be further evaluated as a remedy or adjunct therapy.
In-silico pertains to the utilization of computational models employing diverse techniques to
explore pharmacological hypotheses. These techniques encompass databases, tools for data
analysis, data mining, homology models, machine learning, pharmacophores, quantitative
structure-activity relationships, and network analysis tools.In vitro refers to experiments
conducted outside of a living organism, usually in a lab setting. In vivo, on the other hand,
involves experiments conducted within a living organism and it is widely used in scientific
research.

STATEMENT OF PROBLEM
Prostate cancer is a common type of cancer in males, It begins in the prostate gland, which sits
between the penis and the bladder. .The prostate has various functions. The most
important is producing seminal fluid, which is a component of semen. It also plays
a role in hormone production and helps regulate urine flow.
prostate cancer is the most common cancer affecting males in the United States. The American
Cancer Society (ACS) predicts that in 2021 there will be around 248,530 new diagnoses of
prostate cancer .the following drugs approved for prostrate cancer are abiraterone acetate,
enzalutamide, docetaxel, bicatumide etc have been used in the treatment of prostrate cancer .
However the incidence of prostrate specific antigen (PSA) persistence in localized prostrate
cancer is still very detectable and the cancer spreads to regional lymph nodes, and have
distant metastasis. prostate cancer death rates have been increasing in men of all races
and ethnicities. Having prostrate cancer involves certain effects such as physical side
effects like pain in the bone or during urination, erectile dysfunction etc and also
financial constraints ,as treating the disease at the early stage is key to treatment.The
utilization of medicinal plants in the treatment of cancer has its roots in ethnoveterinary
medicine. . By combining the knowledge obtained from in-silico and in-vitro studies, there is a
potential to discover and optimize new drug candidates with improved efficacy, reduced toxicity,
and enhanced selectivity against cancer.The results of this study will provide rational and new
insights into the potential of this plants as a source of new anti cancer drugs .

AIM OF THE STUDY

The of this study is to identify phytochemicals in nigerian medicinal plants with single or multi
targeting effects against growth of prostrate cancer tumor and prevents metastasis
.
OBJECTIVES OF THE STUDY

identify all the phytochemicals possibly present in Medicinal plants with anticancer activity
- study the druglikeness of the identified phytochemicals
- identify all the possible proteins and enzymes of target in cancer
- prepare the ligands and proteins/enzymes for molecular docking simulation.
- perform validation of docking protocol /blind docking where appropriate.
- perform molecular docking simulation of the phytochemicals
- undertake post docking analysis to identify frontrunner phytochemicals
- perform structural alignment of the target protein from prostrate cancer.
- perform wet lab validation of the frontrunnerS against different cancers .
-to undertake bioactivity prediction of the frontrunner phytocompounds in- silico in comparison
with reference compounds.

JUSTIFICATION OF STUDY
The rich flora of Africa results from a vast difference in environmental and climatic conditions
such as deserts, savannah, and tropical rain forests. Some of these plants have been used in
traditional medicine to treat symptoms of cancer with reports that of all pharmaceutical drugs
used, a quarter of them have been derived from plants originally used in traditional medicine
(Sawadogo et al., 2012). Treatment of patients across Africa varies from one region to another
and this is mostly influenced by the plants, protocols and recipes used. In West Africa, more than
half of plants with anticancer metabolites are shrubs and the explants commonly used are the
roots and stem barks, with methanol extracts contributing approximately 60% of the used
extracts (Sawadogo et al., 2012). (Sawadogo et al., 2012) have shown that phytochemicals with
high cytotoxicity towards many cancer cell lines are diterpenes, triterpenes and
steroids.Conducting in silico studies on Nigerian medicinal plants can contribute to the
development of new anti prostrate cancer drugs . In-silico methods offer a cost-effective and
efficient means to predict potential molecular targets and interactions of bioactive compounds.
By employing techniques such as molecular docking and virtual screening, this study can identify
cancer protein targets that are likely to be modulated by compounds. Such predictions can guide
subsequent experimental studies and contribute to a better understanding of the mechanisms
underlying the anti cancer activity . The findings from this study can pave the way for the
development of new anticancer drugs derived from nigerian medicine plants or its active
constituents. Given the urgent need for new anti cancer drugs,especially those that target
retardation of the tumor growth and the reduction of the prostrate specific antigen , the
discovery of effective compounds can have a significant impact on public health by expanding the
treatment options available and helping to mitigate the challenges associated with prostrate
cancer .

SIGNIFICANCE OF STUDY
the study will help provide the basis for further research targeted at finding phytochemicals
capable of treating prostrate cancer . This research will also aid in finding phytochemicals that
are of therapeutic advantage in the treatment of prostrate cancer .

SCOPE OF STUDY
This research covers the in silico study of phytochemicals with anti prostrate cancer effect and
entails identifying phytochemicals using molecular docking and performing wet lab validation on
the frontrunner phytochemicals .