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Food Chem Toxicol. 2018 Aug;118:675-690. doi: 10.1016/j.fct.2018.06.027. Epub 2018 Jun 18.

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

Author information

1
Department of Biotechnology, Jnana Bharathi Campus, Bangalore University, Bengaluru, 560 056, India.
2
Department of Botany, Molecular Biology Laboratory, Jnana Bharathi Campus, Bangalore University, Bengaluru, 560 056, India.
3
Department of Biochemistry, CSIR-Central Food Technological Research Institute, Mysuru, 570 020, India.
4
Department of Biotechnology, Jnana Bharathi Campus, Bangalore University, Bengaluru, 560 056, India. Electronic address: rlnarn21@gmail.com.

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 up- and 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.

KEYWORDS:

Breast cancer cells; Carotenoids; Cytotoxicity; Doxorubicin; Oxidative stress-mediated apoptosis

PMID:
29920287
DOI:
10.1016/j.fct.2018.06.027
[Indexed for MEDLINE]

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