Low-dose doxorubicin with carotenoids selectively alters redox status and upregulates oxidative stress-mediated apoptosis in breast cancer cells.

Vijay, K. and Sowmya, P. R. Rao and Arathi, B. P. and Baskaran, V. (2018) Low-dose doxorubicin with carotenoids selectively alters redox status and upregulates oxidative stress-mediated apoptosis in breast cancer cells. Food and Chemical Toxicology, 118. pp. 675-690. ISSN 0278-6915

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Abstract

The combination of carotenoids and doxorubicin (DOX) selectively alters oxidative stress-mediated apoptosis in breast cancer cells. Primarily, cytotoxic efficiency of carotenoids (β-carotene, BC; lutein, LUT; astaxanthin, AST; or fucoxanthin, FUCO) either with or without a minimal cytotoxic dose of DOX was evaluated in MCF-7 (0.12 μM) and MDA-MB-231 cells (0.28 μM). The higher cell growth inhibition of BC and/or LUT with DOX was selected for testing in further cell-based assays. Low-dose DOX significantly enhanced cytotoxicity in carotenoid (< 5 μM)-treated cells compared to high-dose DOX (> 1 μM) or carotenoid (20 μM) treatment alone. Depleted glutathione, increased lipid peroxides and increased ROS levels in cells confirmed the cytotoxic effect. Furthermore, mitochondrial dysfunction, cell growth arrest at G0/G1 phase and caspase cascades as well as upand down-regulated expression levels of related proteins (p21, p27, Bax, p53, Bcl-2, and cyclin D1) revealed the synergistic effect of carotenoid and DOX treatment on ROS-mediated apoptosis. These observations demonstrated increased apoptosis in BC + DOX/LUT + DOX-treated cells due to the pronounced pro-oxidant action. Interestingly, normal breast epithelial cells (MCF 10A) exposed to similar treatments resulted in non-significant cytotoxicity. These newly observed mechanistic differences of anticancer drugs on the mitigation of toxicity with carotenoids may provide insight into the targeting of cancer therapy.

Item Type:	Article
Uncontrolled Keywords:	Carotenoids Doxorubicin Breast cancer cells Cytotoxicity Oxidative stress-mediated apoptosis
Subjects:	500 Natural Sciences and Mathematics > 04 Chemistry and Allied Sciences > 14 Carotenoid Chemistry
Divisions:	Dept. of Biochemistry
Depositing User:	Food Sci. & Technol. Information Services
Date Deposited:	03 Sep 2018 06:44
Last Modified:	03 Sep 2018 06:44
URI:	http://ir.cftri.res.in/id/eprint/13838

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