Antioxidants in Cancer Treatment

Abstract

There are many different chemotherapeutic agents used in cancer treatment. Most of the chemotherapeutic drugs can be divided into alkylating agents, antimetabolites, anthracyclines, plant alkaloids, topoisomerase inhibitors, and other antitumour agents. All of these drugs affect cell division or DNA synthesis and function in some way. Several classes of chemotherapy work by producing a reactive oxygen compound or free radical. Alkylating agents work to add alkyl groups to negatively-charged groups. They are known to stop tumor growth through cross-linking guanine nucleobases in strands of DNA, which directly damages the DNA by making it unable to uncoil and separate. The cell, when attacked in this way, is unable to replicate. While it may not die, it also cannot grow. Cyclophosphamide, a cytotoxic alkylating agent, is extensively used as an antineoplastic agent for the treatment of haematological malignancies and a variety of solid tumours, including leukaemia, ovarian cancer and small-cell lung cancer. Cyclophosphamide is bioactivated by hepatic cytochrome P450 enzymes resulting in the formation of phosphoramide mustard and acrolein. The therapeutic effect of cyclophosphamide is attributed to phosphoramide mustard, while the other metabolite, acrolein is associated with toxic side effects. The cellular mechanism of cyclophosphamide toxicity is due to the production of highly reactive oxygen free radicals by these metabolites. It is obvious that high levels of ROS within the body could culminate in oxidative stress. Anthracyclines (or anthracycline antibiotics) are a class of drugs used in cancer chemotherapy derived from Streptomyces bacteria. Anthracycline has three mechanisms of action: inhibits DNA and RNA synthesis by intercalating between base pairs of the DNA/RNA strand, thus preventing the replication of rapidly-growing cancer cells: inhibits topoiosomerase II enzyme, preventing the relaxing of supercoiled DNA and thus blocking DNA transcription and replication: creates iron-mediated free oxygen radicals that damage the DNA and cell membranes. Radiation therapy is another type of cancer treatment that uses ionizing radiation to produce cell death through free radical formation. The cell death occurs by damaging the DNA of cancerous cells. This DNA damage is caused by one of two types of energy: photon or charged particle, directly or indirectly ionizing the atoms which make up the DNA chain. Indirect ionization happens as a result of the ionization of water, forming free radicals, notably hydroxyl radicals, which then damage the DNA. The oxidative stress produced during cancer treatment induces a range of side effects such as hair loss, nausea or vomiting and cardiotoxicity. Several authors believe that the use of antioxidants during cancer treatment can reduce these side effects. However, there is a