Abstract: The term “antioxidant” coined in 1920 denote substance that fight against any sort of oxidation process (chemical process in which oxygen is caused to combine with other molecules. Most oxidations occur with the liberation of large amounts of energy). The prefix "anti" of the word antioxidants indicate that it works “against” or “in opposition” to the activity of oxidants. Here oxidants indicate free radicals. Free radicals have attracted a great deal of attention in recent years. They are mainly derived from oxygen (reactive oxygen species/ROS) and nitrogen (reactive nitrogen species/RNS), and are generated in our body by various endogenous systems, exposure to different physicochemical conditions or patho- physiological states. Free radicals can adversely alter lipids, proteins and DNA (Deoxyribose nucleic acids) and have been implicated in aging and a number of human diseases including cancer. Antioxidants applications in this regard have become an interesting and introspective arena of research. Antioxidants can fight against these free radicals and protect the body from the various adversaries. When talking of antioxidants, the most widely acclaimed and discussed terminology are the dietary and herbal natural antioxidants which are mostly from plant sources. Scientific evidence strongly holds the promising concept of application of antioxidants against Cancer and also against the side-effects of Cancer Chemotherapy. Antioxidants like Vitamin C, Vitamin E, Quercetin, Curcumin and many others have immense potential to play an important part in Chemotherapy and also in fighting against wide range of cancers.
Keywords: Antioxidant; Cancer; Genetic damage; Vitamin C; Vitamin E; Curcumin; Quercetin
Cancer is a large, heterogeneous class of diseases in which a group of cells display uncontrolled growth, invasion that intrudes upon and destroys adjacent tissues, and often metastasizes, wherein the tumor cells spread to other locations in the body via the lymphatic system or through the blood stream. Cancer can affect people of all ages. The origin of Cancer may be genetical, hereditary, life-style, diet and certain harmful habits (smoking, alcohol, tobacco and betel nut consumption) which may trigger the disease. The overall risk of developing cancer generally increases with age, at least up to age 80-85 yr. In 2007, cancer caused about 13% of all human deaths worldwide (7.9 million). Rates are rising as more people live to an old age and as mass lifestyles change is occurring in the developing world.
Most cancers can be treated if diagnosed at an initial stage, with the most important modalities being Chemotherapy (treatment with chemicals), Radiotherapy (treatment with radiation) and Surgery (removal of cancer developed organs and tissue). The use and application of drugs synthesized or procured from natural or synthetic sources for cancer inhibition and cure is known as “chemotherapy” and the drugs are more commonly named as chemotherapeutic drugs. Cancer chemoprevention is fast becoming a lucrative approach. Chemotherapeutic agents can be divided into several categories: alkylating agents (e.g., Mitomycin C, Cyclophosphamide), antibiotics which affect nucleic acids (e.g., Doxorubicin, Bleomycin), mitotic inhibitors (e.g., Vincristine, Vinblastine, Taxol), platinum compounds (e.g., Cisplatin), camptothecin derivatives (e.g., Topotecan), antimetabolites (e.g., 5-fluorouracil), biological response modifiers (e.g., Interferon), and hormone therapies (e.g., Tamoxifen). Most of these drugs are FDA (US-Food and Drug administration) approved which after passing through rigorous safety tests are marketed and sold but unfortunately after passing through such rigorous tests when these drugs are retested in research laboratories, they show high level of toxicity. The visible physical toxicity includes nausea, diarrhea, dysentery, alopecia, weakness, fatigue but more importantly serious toxicity is generated to the normal cells and their genetic composition (DNA). One of the major challenges with chemotherapy is damage to surrounding healthy organs and tissue as most of the marketed anti-cancer drugs are designed simply to destroy cells and as they are not specific to cancer cells alone. Infact they act on both normal and cancer cell and destroy it in a similar fashion which is not at all feasible and is the major drawback of chemotherapy. Cancer drugs generate very high level of free radicals which are responsible for bringing genetical side-effects, faulty protein formation and secondary cancers. Free radicals are atoms or groups of atoms with an odd (unpaired) number of electrons and can be formed when oxygen interacts with certain molecules. Once formed these highly reactive radicals can start a chain reaction. Their chief danger comes from the damage they can do when they react with important cellular components such as DNA (Deoxyribose nucleic acids), or the cell membrane. Cells may function poorly or die if this occurs. Hence 35 years after the 'war on cancer' was declared, the discovery and application of anticancer drugs still remains a highly challenging endeavor. To cope up with the unsafe and unpleasant side-effects of chemotherapy the holistic concept of alternative medicine and combination therapy came into existence. Since it is not possible to avoid mutagens (agents which causes change in the normal DNA), neither it is possible to stop application of drugs for cancer treatment, the only path out is to mitigate or suppress their activity and undo their damage by other means. This is the reason behind the popularization and increase of scientific interest in the concept of alternative therapy. The compounds employed in alternative therapy are majorly dietary antioxidants. Science shows a very strong correlation between antioxidants intake and minimization of chemotherapy side-effects and Cancer prevention.
2. Foods and antioxidants:
Food contains many antioxidants some of which may not even be known to science. Foods are a dependable and right source for antioxidants specially the fresh bright colored organic produce. Foods are economical way of getting antioxidants. The major antioxidants are from the natural phytochemical source as well as known Vitamins and plant extracts, present in fruit, vegetables, herbs, spices and beverages. Antioxidants like Vitamin B (asparagus, broccoli, spinach, bananas, potatoes, dried apricots, dates and figs) Vitamin C (oranges, lemon, Strawberries, Kiwi fruit, Mango), Vitamin E (avocados, tomatoes, sweet potatoes, spinach, watercress, brussels sprouts, blackberries, mangoes) Curcumin (turmeric), Quercetin (onions, tea), Resveratrol (grapes), Allyl cysteine (ginger), Lycopene (tomatoes) are all free radical scavengers, and deliver protection by inhibiting oxidative DNA damage.
2.1. Vitamin C, its application in Cancer and Chemotherapy:
The most common and easily available natural antioxidant is the water soluble glucose derivative Vitamin C (C6H8O6). In 1747, Scottish naval surgeon James Lind discovered that a nutrient (now known as Vitamin C) in citrus fruits prevented the disease called scurvy. It is a powerful reducing agent and present widely in tropical diet rich in citrus fruits (e.g. oranges and lemons) and vegetables. Vitamin C has been extensively tested in vitro (Latin for” within glass” i.e. cells and tissues grown in culture flasks/petridishes) and in vivo (Latin for "within the living system") for its ability to prevent the adverse effects of, decrease resistance to, and increase the effects of chemotherapeutic agents. In one work in laboratory rats antioxidant Vitamin C was used to study its protective role against Cisplatin toxicity. It was observed that Vitamin C inhibited Cisplatin induced chromosomal damage by about 41% and 70% when compared to animals treated only with Cisplatin alone (Antunes et. al., 2000). Later in yet another work with Cisplatin, it was observed that Vitamin C used in the human lymphocytes culture reduced the clastogenic effects of the drug (Nefic, 2001). In one of our research findings (Mazumdar et. al., 2011) it was shown that Vitamin C minimizes the genetical side effects of cancer drug Mitomycin C in mammalian test model and a high dose of 500 milligram per kilogram body weight showed highest level of protection to mammalian cells against the effects of the drug. Genetical toxicity induced by some common pharmaceutical like norfloxacin and Chloroquine, could also be minimized by combination therapy with Vitamin C (shown in the work of Alba et. al., 2008 and in one of our works, Roy et. al., 2008). Vitamin C may be responsible for the sharp decline in stomach cancer, which used to be the most prevalent form of cancer in the USA. Vitamin C in breakfast orange juice probably blocked the formation of carcinogens (called nitrosamines) in the stomachs of people eating bacon or ham and eggs. The Japanese who do not generally drink orange juice continue to have high rates of cancer. Association between colorectal cancer mortality and supplementation of Vitamin C and Vitamin E was examined in the American’s Cancer Society’s Cancer Prevention Study II cohort. In the analyses it was observed that use of Vitamin C for 10 or more years decreased the risk of colorectal cancer mortality (Jacob et. al., 2001).
At a minimum it is advisable to take 250 milligrams of Vitamin C per day, in divided doses. 500 milligrams per day would be even better. Those actively fighting cancer should take 1000-2000 milligram of Vitamin C in divided doses.