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Role of free Radicals


Millions of patients throughout the world suffer from cancer. Recent evidence suggests regional variance of cancer with lung, breast, colon, uterus and prostate cancers being prevalent in developed countries compared to cervical, mouth/pharynx, esophageal and liver cancers being prevalent in the developing world. Evidence suggests that cancer development occurs in two stages, initiation and promotion. Initiation involves a permanent, irreversible genetic change in the cell’s DNA. This generally causes DNA strand brakes, which can lie dormant in the cell but do not alone cause cancer. Promotion elicits the second stage of carcinogenesis, which stimulates the cell infiltration, transforming it to a cancerous cell. This process is reversible and may require continued stimulation to promote mutations. Many components have both initiating and promoting activities, however, free radicals are thought to act principally as promoting agents. Superoxide radicals and many peroxides are tumor promoters whereas some antioxidants act as anti-promoters and anti-carcinogens. Free radicals have been associated with gross chromosomal damage and also inhibition of the biological natural repair system. Free radicals and ROS can alter gene expression by mobilization of calcium stores, which activate a variety of cellular kinases, phosphatases and transcription factors. Lipid peroxidation by free radicals and ROS has also been implicated as a causative factor in cancer development.

  1. Brown NS. Bicknell R. Hypoxia and oxidative stress in breast cancer. Oxidative stress: its effects on the growth, metastatic potential and response to therapy of breast cancer. Breast Cancer Research. 3(5):323-7, 2001.

  2. Crumpton TL. Seidler FJ. Slotkin TA. Generation of reactive oxygen species by xanthine derivatives in MDA-MB-231 human breast cancer cells. Breast Cancer Research & Treatment. 66(2):143-6, 2001

  3. Ambrosone CB. Sweeney C. Coles BF. Thompson PA. McClure GY. Korourian S. Fares MY. Stone A. Kadlubar FF. Hutchins LF. Polymorphisms in glutathione S-transferases (GSTM1 and GSTT1) and survival after treatment for breast cancer. Cancer Research. 61(19):7130-5, 2001

  4. Bauer G. Lactobacilli-mediated control of vaginal cancer through specific reactive oxygen species interaction. Medical Hypotheses. 57(2):252-7, 2001

  5. Kampa M. Hatzoglou A. Notas G. Damianaki A. Bakogeorgou E. Gemetzi C. Kouroumalis E. Martin PM. Castanas E. Wine antioxidant polyphenols inhibit the proliferation of human prostate cancer cell lines. Nutrition & Cancer. 37(2):223-33, 2000.

  6. Chang MC. Ho YS. Lee PH. Chan CP. Lee JJ. Hahn LJ. Wang YJ. Jeng JH. Areca nut extract and arecoline induced the cell cycle arrest but not apoptosis of cultured oral KB epithelial cells: association of glutathione, reactive oxygen species and mitochondrial membrane potential. Carcinogenesis. 22(9):1527-35, 2001

  7. Zhang Z. Huang C. Li J. Leonard SS. Lanciotti R. Butterworth L. Shi X. Vanadate-induced cell growth regulation and the role of reactive oxygen species. Archives of Biochemistry & Biophysics. 392(2):311-20, 2001

  8. Zieba M. Nowak D. Suwalski M. Piasecka G. Grzelewska-Rzymowska I. Tyminska K. Kroczynska-Bednarek J. Kwiatkowska S. Enhanced lipid peroxidation in cancer tissue homogenates in non-small cell lung cancer. Monaldi Archives for Chest Disease. 56(2):110-4, 2001

  9. Zhao Y. Xue Y. Oberley TD. Kiningham KK. Lin SM. Yen HC. Majima H. Hines J. St Clair D. Overexpression of manganese superoxide dismutase suppresses tumor formation by modulation of activator protein-1 signaling in a multistage skin carcinogenesis model. Cancer Research. 61(16):6082-8, 2001

  10. Gouaze V. Mirault ME. Carpentier S. Salvayre R. Levade T. Andrieu-Abadie N. Glutathione peroxidase-1 overexpression prevents ceramide production and partially inhibits apoptosis in doxorubicin-treated human breast carcinoma cells. Molecular Pharmacology. 60(3):488-96, 2001

  11. Vrablic AS. Albright CD. Craciunescu CN. Salganik RI. Zeisel SH. Altered mitochondrial function and overgeneration of reactive oxygen species precede the induction of apoptosis by 1-O-octadecyl-2-methyl-rac-glycero-3-phosphocholine in p53-defective hepatocytes.FASEB Journal. 15(10):1739-44, 2001

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