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Cancer Preventive and
Therapeutic Properties of Fruits
and Vegetables: An Overview
Chandrasekharan Guruvayoorappan, Kunnathur Murugesan Sakthivel,
Ganesan Padmavathi, Vaishali Bakliwal, Javadi Monisha
and Ajaikumar B. Kunnumakkara*
INTRODUCTION
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.
Cancer
Cancer has 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 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.
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 cancer-causing 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.
Figure 1.1: Progressive model for multi-stage carcinogenesis.
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 ...
