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Combined efficacy of tamoxifen and coenzyme Q10 on the status of lipid peroxidation and antioxidants in DMBA induced breast cancer

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Abstract

An increasing amount of experimental and epidemiological evidence implicates the involvement of oxygen derived radicals in the pathogenesis of cancer development. It is well known that chemical carcinogenesis is multistage process. Free radicals are found to be involved in both initiation and promotion of multistage carcinogenesis. Tamoxifen (TAM) is a potent antioxidant and a non-steroidal antiestrogen drug most used in the chemotherapy and chemoprevention of breast cancer. Besides its anticarcinogenic potential, it also produces some adverse toxic side effects, while taken for a long time. In order to minimise the side effects and to improve the antioxidant efficacy of tamoxifen, coenzyme Q10 (CoQ10) was added. Hence the present study was designed to investigate the combined efficacy of TAM along with CoQ10 in 7, 12 dimethyl benz(a)anthracene (DMBA) induced peroxidative damage in rat mammary carcinoma. The experimental setup comprised of one control and five experimental groups and it was carried out in adult female Sprague-Dawley rats. Mammary carcinoma was induced by oral administration of DMBA (25 mg kg−1 body wt) and the treatment was started by the oral administration of TAM (10 mg kg−1 body wt day−1) and CoQ10 (40 mg kg−1 body wt day−1) dissolved in olive oil and continued for 28 days. Rats induced with DMBA showed a decline in the thiol capacity of the cell accompanied by high malondialdehyde content levels along with lowered activities of antioxidant status (superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione). In contrast, glutathione metabolising enzymes (glutathione reductase, glucose-6-phosphate dehydrogenase and glutathione-S-transferase) were increased significantly in chemically induced carcinoma bearing rats. Administration of TAM along with CoQ10 restored the activities to a significant level thereby preventing cancer cell proliferation. This study highlights the increased antioxidant enzyme activities in relation to the susceptibility of cells to carcinogenic agents and the response of tumour cells to the chemotherapeutic agents.

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Authors and Affiliations

  1. Department of Medical Biochemistry, Dr. A.L. Mudaliar Post-Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, India

    Selvanathan Saravana Perumal & Panchanadham Sachdanandam

  2. Department of Pathology, Dr. A.L. Mudaliar Post-Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, India

    Palanivelu Shanthi

  3. Department of Medical Biochemistry, Dr. A.L.M. Post-Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600 113, India

    Panchanadham Sachdanandam

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  1. Selvanathan Saravana Perumal
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Correspondence to Panchanadham Sachdanandam.

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Perumal, S.S., Shanthi, P. & Sachdanandam, P. Combined efficacy of tamoxifen and coenzyme Q10 on the status of lipid peroxidation and antioxidants in DMBA induced breast cancer. Mol Cell Biochem 273, 151–160 (2005). https://doi.org/10.1007/s11010-005-0325-3

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