ANTIOXIDANT THERAPY FOR CANCER
ANTIOXIDANT THERAPY FOR CANCER
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Cancer is the leading cause of mortality worldwide, accounting for almost 13% of deaths in the world. Among the conventional cancer treatments, chemotherapy is most frequently carried out to treat malignant cancer rather than localized lesions which is amenable to surgery and radiotherapy. However, anticancer drugs are associated with a plethora of side effects. To curb these undesired side effects, several dietary supplements have been tested, amongst which antioxidants have gained increasing popularity as adjuvant in chemotherapy. However, many oncologists discourage the use of antioxidant rich food supplements because these may interfere with the modalities which kill cancer by generating free radicals. In the present review, all studies reporting concomitant use of several antioxidants with chemotherapy are indiscriminately included and discussed impartially. Antioxidants prevent cellular damage by reacting and eliminating oxidizing free radicals thereby finding relevance in adjuvant chemotherapy. The use of antioxidant supplements by patients with cancer is estimated to be between 13 and 87%.
Chemotherapy is used primarily to treat systemic disease rather than localized lesions that are amenable to surgery or radiation. It uses antineoplastic agents in an attempt to destroy tumor cells by interfering with cellular function including replication. These drugs result in causing lethal injury to DNA which further leads to malignant cell death via apoptosis. In cancer treatment, mode of action of certain chemotherapeutic agents involves generation of free radicals to cause cellular damage and necrosis of malignant cells. Nausea and vomiting which usually occurs within 24 h of drug administration can be amongst the most disturbing and unpleasant side effects induced by chemotherapy. If persistent, vomiting may lead to dehydration, electrolyte disturbances, metabolic alkalosis, weakness, weight loss, cachexia, nutritional impairment and physical injury such as esophageal tears and fractures. Cardiac damage is the dose-limiting toxicity of the anthracycline group of antitumor antibiotics related anthraquinones, damage to the liver is a complication of many drugs. Most of the oxygen taken up by the cells is converted to water by the action of cellular enzymes. However, some of these enzymes leak electron into oxygen molecules and lead to the formation of free radicals. They are also formed during normal biochemical reactions involving oxygen. ROS is a collective term used for a group of oxidants, which are either free radicals or molecular species capable of generating free radicals. There are two important sources of free radical formation. Depending upon their nature, chemotherapy induced ROS reacts with biomolecules to produce different types of secondary radicals like lipid, sugar, nitrogenous base, amino acid derived radicals and thiyl radicals. These radicals in presence of oxygen are converted to peroxyl radicals that often induce chain reactions. The biological implications of such reactions depend on several factors like nature of the substrate, site of generation, activation of repair mechanisms, redox status etc. In order to check the activities of ROS/RNS in vivo and maintain cellular redox homeostastis, antioxidant system has evolved. Antioxidants are substances that may protect cells from the damage caused by free radicals, and may play a role in heart disease, cancer and other diseases.
Role of antioxidants are controversial in cancer therapy because of two very imperative features “First, there are two different kinds of antioxidants doses used based on which the data on the role of antioxidants in cancer therapy can be categorized as: a preventive dose, which is a low dose, and a therapeutic dose, which is a high dose. For the preventive dose, the data has shown protection of normal cells and tumor cells. For the therapeutic dose, the data shows that it inhibits the growth of cancer cells but not the normal cells. Therefore researchers are looking at data for preventive doses, which is perplexing. Cancer patients suffer from vitamin deficiencies, particularly of folic acid, vitamin C, pyridoxine and other nutrients because of poor nutrition and treatment. Chemotherapy reduces serum levels of antioxidant vitamins and minerals due to lipid peroxidation and thus produces higher level of oxidative stress. Therefore, supplementation of certain antioxidants and nutrients can help to enhance the health status of patients undergoing continous regime of chemotherapy. Use of antioxidants can be beneficial in this respect as they minimize the burden of free reactive radicals in cells and thus can decrease the duration of chemotherapy regimens. Despite nearly two decades of research investigating the use of dietary antioxidant supplementation during conventional chemotherapy, controversy remains about the efficacy and safety of this complementary treatment.