ROLE OF ANTIOXIDANT IN CANCER TREATMENT: A REVIEW
Dhakar Mukesh*, M. Jeevan, Kumar Neeraj, Dashora Ashok
Geetanjali Institute of Pharmacy,
(Department of Pharmaceutical Chemistry.)
AirPort Road, Dabok, Udaipur (Rajasthan)- 313022
Antioxidants are essential and important for plants and animals’ sustenance. They are substances that protect cells from the damage caused by unstable molecules known as free radicals. Cancer develops when cells multiply in the presence of oxidation and other damage. Certain "antioxidant" substances, such as vitamin C, are able to exploit the differences between cancer and healthy cells; they kill cancer cells while helping healthy cells. Antioxidants are substances that may protect cells from the damage caused by unstable molecules known as free radicals. Free radical damage may lead to cancer. Antioxidants interact with and stabilize free radicals and may prevent some of the damage free radicals Examples of antioxidants include Quercetin Curcumin Beta-carotene, Lycopene, Vitamins C, E, and A, and other substances. Epidemiological studies have consistently shown that regular consumption of fruits and vegetables is strongly associated with reduced risk of developing chronic diseases, such as cancer and cardiovascular disease.
Reference Id: PHARMATUTOR-ART-1968
Antioxidants neutralize free radicals as the natural by-product of normal cell processes.
Free radical formation can leads due to the Exposure of various environmental factors, including tobacco smoke and radiation and etc. The most common form of free radicals in Humans is oxygen. When an oxygen molecule becomes electrically charged causing damage to the DNA and other Cell such damage may be irreversible and may be causes many disorders like as Cancer. Antioxidants are neutralize the electrical charge and prevent the transportation of electrons from other molecules to free radicals.
DNA is a major target of free radical damage. The types of damages induced are many and include strand breaks (single or double strand breaks) damage yielding products such as 8-hydroxyguanosine, thymine glycol or abasic sites. These damages can result in mutations that are heritable change in the DNA that can yield cancer. The involvement of free radicals with tumor suppressor genes and proto-oncogenes suggest their role in the development of different human cancer.
produced in the body (endogenous) and others obtained from the diet (exogenous Humans have evolved with antioxidant systems for protection against free radicals and ROS. These systems include some antioxidants).
Many clinical trials published and reached differing conclusions about the effect of antioxidants on cancer.
1. The first large randomized trial on antioxidants and cancer risk was the Chinese Cancer Prevention Study, published in 1993. This trial investigated the effect of a combination of beta-carotene, vitamin E, and selenium on cancer in healthy Chinese men and women at high risk for gastric cancer. The study showed a combination of beta-carotene, vitamin E, and selenium significantly reduced incidence of both gastric cancer and cancer overall. 
2. A 1994 cancer prevention study entitled the Alpha-Tocopherol (vitamin E)/ Beta-Carotene Cancer Prevention Study (ATBC) demonstrated that lung cancer rates of Finnish male smokers increased significantly with beta-carotene and were not affected by vitamin E. 
Cancer development can be described by three stages: initiation, promotion and progression, and ROS can act in all these stages of carcinogenesis  . It is also well established that free radicals are known to react with all components of DNA, thus damaging its bases and the deoxyribose backbone  causing mutations in crucial genes, which ultimately may lead to cancer. 
A high level of oxidative stress can induce apoptosis or even necrosis; however, a low level of oxidative stress can stimulate cell division and thus promote tumor growth.  ROS probably enhance the final irreversible stage of carcinogenesis, which is characterized by accumulation of additional genetic damage, leading to the transition of the cell from benign to malignant.
Three large-scale clinical trials continue to investigate the effect of antioxidants on cancer
1. The Women’s Health Study (WHS) is currently evaluating the effect of vitamin E in the primary prevention of cancer among U.S. female health professionals age 45 and older. The WHS is expected to conclude in August 2004
2. The Selenium and Vitamin E Cancer Prevention Trial (SELECT) is taking place in the United States, Puerto Rico, and Canada. SELECT is trying to find out if taking selenium and/or vitamin E supplements can prevent prostate cancer in men age 50 or older. The SELECT trial is expected to stop recruiting patients in May 2006.
3. The Physicians' Health Study II (PHS II) is a follow up to the earlier clinical trial by the same name. The study is investigating the effects of vitamin E, C, and multivitamins on prostate cancer and total cancer incidence. The PHS II is expected to conclude in August 2007.[9_11]
Last stages cancer can’t treated with antioxidants suppliments. So ant oxidative nutritional supplements as cancer preventatives is not actual therapies .The great Caltech chemist, Linus Pauling, who near the end of his illustrious career wrote a book with Ewan Cameron in 1979, Cancer and Vitamin C, about vitamin C's great potential as an anti-cancer agent.. But At the time of his death from prostate cancer in 1994, at the age of 93, Linus was taking 12 g of vitamin C every day. late-stage cancer'. vast number of nutritional intervention trials using the antioxidants β-carotene, vitamin A, vitamin C, vitamin E and selenium have shown no obvious effectiveness in preventing gastrointestinal cancer..
The cytotoxic action (side/adverse effect of anti cancer agents) of many anticancer drug including like as 5-fluorouracil, vincristine, doxorubicin, cisplatin and were found to be increased with co administration or in presence of vitamin E and the cytotoxic effect of Antineoplastics agents Bleomycin, Paclitaxel and darcarbazine were found to be increased with co administration or in presence of vitamin C during in vitro studies through inhibition of the effects of lipid peroxidise on cell growth. .
Molecular Studies of Natural Antioxidants:
Different types of natural antioxidants are present in fruit and vegetables they have synergistic interactions that are important due to their activity and regenerative potential. For example,ascorbate can regenerate into α-tocopherol.  Interactions is known as the “antioxidant network”.
Tumor necrosis factor-alpha (TNF-α) is a cytokine that, under normal conditions, induces inflammation, tumor inhibition, and apoptotic cell death. However, when the former undergoes deregulation, it acts as a breast tumor promoter, enhancing the proliferation of chemically induced mammary tumors. .
Phenolic antioxidants can block the increase of TNF- α at the transcriptional level in the nucleus, which suggests the molecular mechanism of phenolic antioxidants through control of cytokine induction. .
Nomenclature and Classification of Antioxidants:
Table 1 lists categories in which various antioxidants have been characterized.
Quercetin (3,3’,4’,5,7-pentahydroxyflavone)is one of the most frequently studied bioflavonoid. Flavonoids are polyphenolic compounds possessing 15 carbon atoms, two benzene rings joined by a linear three carbon atom chain (structure A). The chemical structure of flavonoids are based on a C15 skeleton with a chromane ring bearing a second aromatic ring B in position 2, 3 or 4 (structure B). Quercetin have multiple pharmacological and medicinal action and uses as anti-inflammatory, anti-allergic, antiviral, antithrombotic, anti-mutagenic and antineoplasti agents. 
A number of its actions make it a potential anti-cancer agent, including cell cycle regulation, interaction with type II estrogen binding sites, and tyrosine kinase inhibition. .
Its reputation as an antioxidant stems from the reactivity of phenolic compounds with free radical species to form phenoxy radicals which are considerably less reactive
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