Introduction
Cancers have been known since human societies first recorded their activities,
but the formal study of cancer (i.e., oncology) was first documented in the
seventeenth century. Cancer can be defined as a disease of an uncontrolled division
of abnormal cells. Cancer not only affects human and higher mammals,
but it affects almost all the multicellular organisms — animals as well as
plants. Nearly 175 years ago, the German microscopist, Johannes Müller, was
the first to show that cancers were made up of cells. After this finding, an
enormous amount of information has been amassed about this disease.
Markedly, in the past two decades, rapid technological advancement has aided
us as we dissever the cancer genomes, transcriptome, and proteome, in detail.
Cancer is one of the leading causes of death worldwide, accounting for one
in every eight deaths — more than HIV/AIDS, tuberculosis, and malaria.
According to GLOBOCAN (2008), approximately 12.7 million people are
diagnosed with cancer every year, causing approximately 7.6 million
deaths.1 During the past several decades, numerous epidemiological and
experimental studies have resulted in significant progress in understanding
the molecular mechanisms of cancer development. These studies also suggest
that lifestyle plays a critical role in the development of this disease. For
instance, obese and diabetic patients have a greater susceptibility to cancer
than lean and non-diabetic individuals. Moreover, it has been well established
that a diet rich in saturated fats and red meats and low in fresh fruits,
vegetables, and whole grains has been shown to increase the risk of cancer.
According to the United States National Institutes of Health, “12 servings of
fruits and vegetables a day” can prevent common diseases including cancer.
This clearly shows the importance of fruits and vegetables in the prevention
of this disease. In this chapter, we will discuss the common fruits and vegetables
that are known to have anticancer properties. However, we will first
place the subject in context, discussing the history, classification and development
of cancer and its different treatment modalities.
Classification of Cancer
The classification of cancer is highly complicated due to the presence of a
wide variety of human cancers that arise in almost every tissue in our
body. Oncologists and cancer biologists classify cancers based on the tissues
of origin, regardless of organ location, focusing on similarities in
cellular structure and function among tumors. A tumor is an abnormal
mass of tissue that can be either benign (non-cancerous) or malignant
(cancerous). Tumors can be either a solid mass comprised of epithelial or
mesenchymal cells that are usually immobile, or they can be a liquid sac,
which includes leukemias and lymphomas comprising neoplastic cells
whose precursors are usually motile.2 Further, pathologically, cancers are
classified into four different types:
(1) Carcinoma: originates from epithelial cells in the skin or in other tissues
that line or cover internal organ.
2) Sarcoma: originates in bone, cartilage, fat, muscle, blood vessels, or
other connective or supportive tissue.
(3) Leukemia: originates in blood-forming tissues of the body such as
bone marrow, causing abnormal proliferation of blood cells usually,
white blood cells (leukocytes).
(4) Lymphoma: originates in the cells of the immune system, also termed
as cancers of the lymphoid organs such as the lymph nodes, spleen,
and thymus, which produce and supply infection-fighting cells.3
Development of Cancer: Multi-Stage Carcinogenesis
Carcinogenesis, the process of cancer development, is a multi-stage process.
Generally, cancer starts with a mutational event (i.e., genetic
changes) in a single normal cell; then, it will develop into a multi-stage
process through the acquisition of further mutations that are inherited by
the progeny of that cell when it divides, thus cancer is also termed as
clonal disease (Fig. 1.1). In higher animals or humans, the use of a cancercausing
agent ( carcinogen) does not lead to the immediate production of
a tumor. Rather, it will arise after a long latent period. Berenblum and
Shubik in 19404 showed that there are three major stages involved in the
process of carcinogenesis. The first is initiation, which involves the mutagenic
effects of the carcinogen. The second stage is promotion, which may
be induced by several agents that are not directly carcinogenic (promoters)
and may be followed by the chronic treatment of the carcinogens.
The third stage is progression in which benign tumors either spontaneously,
or followed by additional treatment of the carcinogens, will
progress to invasive tumors. The latent period between initiation and the
appearance of tumors is very long. After exposure to carcinogens, it may
take more than 20 years before tumors develop in humans. Even in animals,
if given heavy doses of carcinogens, it may take up to one-third of
the animal’s total lifespan before tumors appear. Initiation and progression
of cancer depend upon several external and internal factors such as
tobacco use, exposure to infectious organisms, radiation, hormones,
inherited mutations, and immune conditions. Uncontrolled mutations
and selective expansion of cancer cells lead to tumor growth and progression,
eventually spreading to other locations of the body. This proliferation of
cancer cells is termed as metastasis.
Treatment Strategies for Cancer
Options for the treatment of cancer are expanding at a high rate. Current
strategies for treating cancer involve surgery, radiation, or drugs — either
singly or in combination.5
Surgery
Surgical treatment involves excision of tumor, the most frequently
employed form of tumor therapy worldwide. In recent years, surgery combined
with other treatment approaches such as chemotherapy and
radiation therapy, has enhanced the effectiveness of cancer treatment. The
side effects of the surgical treatment depend upon the location of the
tumor, the patient’s general health, type of operation, and other factors.
Radiation therapy
Radiation therapy involves the exposure of the body to ionizing radiations
like X-rays and γ-rays to selectively target the cancer tissue. It
includes the uptake of radioactive iodine, which travels in the blood to kill
the cancer cells and is referred to as systemic radiation therapy. Additional
types of radiation therapy include external beam radiation therapy (e.g.,
X-ray tubes, cobalt gamma rays, and linear accelerators), brachytherapy
(caesium-137, iodine-125, or iridium-192), and radiopharmaceuticals
that target specific tissues. Currently, much research focuses on radiosensitizers
and radioprotectors. Radiosensitizers are drugs which make the
cancer cells more sensitive to the radiation therapy, in addition to anticancer
drugs like 5-fluorouracil and cisplastin. Natural radioprotectors
like rutin and quercetin, among others, are drugs that protect the normal
cells from damage and promote the repair of normal cells caused by
radiation therapy.6
Chemotherapy
Chemotherapy is the use of chemicals to treat cancer. Research over the
past several decades has developed many chemotherapeutic agents for
the treatment of cancer. These include mustard gas, cyclophosphamide,
vincristine, vinblastine, taxol, tyrosine kinase inhibitors, etc. The common
side effects of chemotherapy include nausea and vomiting, hair
loss (alopecia), suppression of white blood cells and production of
platelets (myelosuppression), diarrhea, and decreased spermatogenesis/
ovarian follicle formation. Long-term toxicity and the risk of developing
resistance to chemotherapy are formidable hindrances that could
limit the chronic application strategy in the chemotherapy of several
cancers.
Cancer Chemoprevention
Cancer chemoprevention is a relatively new area in the field of oncology that
uses naturally occurring or synthetic agents to inhibit the process of carcino
genesis or to slow down the progression of cancer. Chemoprevention helps
to lower the risk of developing invasive or clinically significant diseases.
There are three different types of cancer chemoprevention: (1) primary prevention
in high-risk healthy individuals; (2) cancer prevention in individuals
who have developed pre-malignant lesions; and (3) prevention of secondary
forms of cancers in patients already treated for a primary cancer. The final
endpoint of all three aspects of chemoprevention is the attainment of clinical
evidence for cancer reduction.7 Cancer chemopreventive agents prevent the
transformation of pre-malignant lesions to form malignant tumors by
modulating cell proliferation and/or differentiation.8 It has been recommended
that these agents be administered over a long time period to
individuals who have an increased risk of developing cancer; however, even
minor adverse side effects would be unacceptable.9 It is now well established
that the compounds present in fruits and vegetables have fewer side effects
and are, therefore, ideal for cancer chemoprevention.