Journal
FOOD AND CHEMICAL TOXICOLOGY
Volume 118, Issue -, Pages 675-690Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2018.06.027
Keywords
Carotenoids; Doxorubicin; Breast cancer cells; Cytotoxicity; Oxidative stress-mediated apoptosis
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Funding
- DST-SERB, Govt. of India [SB/EMEQ-233/2013]
- Department of Biotechnology, Bangalore University, UGC-SAP [F.4-8/2018/DRS-II/SAP-II]
- DST-FIST [SR/FST/LS1-393/2008]
- CSIR (New Delhi, India)
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The combination of carotenoids and doxorubicin (DOX) selectively alters oxidative stress-mediated apoptosis in breast cancer cells. Primarily, cytotoxic efficiency of carotenoids (beta-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 mu M) and MDA-MB-231 cells (0.28 mu M). 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 mu M)-treated cells compared to high-dose DOX ( > 1 mu M) or carotenoid (20 mu M) treatment alone. Depleted glutathione, increased lipid peroxides and increased ROS levels in cells confirmed the cytotoxic effect. Furthermore, mitochondrial dysfunction, cell growth arrest at GO/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.
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