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Department of Medical Oncology, Institute Rotary Cancer Hospital (A.K.P., V.K.), All India Institute of Medical Sciences, New Delhi INDIA
Department of Biochemistry (N.S., N.K., V.G.R.), All India Institute of Medical Sciences, New Delhi INDIA
Center for Vitamin and Cancer Research, University of Colorado Health Sciences Center, Denver, Colorado (K.N.P.)
Address correspondence to: Dr. Neeta Singh, Additional Professor, Dept. of Biochemistry, All India Institute of Medical Sciences (AIIMS), New Delhi 110 029, INDIA. E-mail: singh_neeta{at}hotmail.com
Objective: Antioxidants have been shown to enhance the effect of certain chemotherapeutic agents on tumor cells in culture. However, this effect differs depending upon the type of tumor and the drugs. In this study, the objective was to see whether pretreatment with antioxidant mixture could enhance the cytotoxic and apoptotic effect of commonly used chemotherapeutic agents, paclitaxel and carboplatin for the treatment of NSCLC.
Methods: Human lung squamous cell carcinoma cell line, H520, was treated with antioxidant mixture (vitamin C, vitamin E and beta carotene), paclitaxel and carboplatin, individually and in combination of different doses in different sequences. Growth inhibition and induction of apoptosis was studied by morphological changes, MTT assay and flow-cytometric analysis.
Results: The antioxidant mixture by itself led to 15% apoptosis in H520 cells. Paclitaxel treatment 24 hours prior to carboplatin caused 54% apoptosis, more than that produced by simultaneous treatment with both agents (40%). A statistically significant improvement in the degree of apoptosis, induced by paclitaxel and carboplatin combination, was seen when the cells were pretreated with antioxidant mixture immediately before paclitaxel exposure (70%) or 24 hours before paclitaxel exposure (89%).
Conclusion: The data suggests that the apoptotic effects of paclitaxel and carboplatin are enhanced by pretreatment with the antioxidant mixture. Thus, the most promising sequence of these agents, which emerged in this study, was pretreatment with antioxidant mixture for 24 hours followed by paclitaxel treatment for 24 hours followed by carboplatin exposure for 24 hours.
Key words: antioxidant mixture, chemotherapy, lung cancer, India, apoptosis
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