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

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Kariyappa Vijay, . and Raghavendra-Rao Sowmya, Poorigali and Bangalore Prabhashankar Arathi, . and Shivaprasad shilpa, . and Hulikere Jagdish Shwetha, . and Marisiddaiah Raju, . and Vallikannan Baskaran, . and Rangaswamy Lakshminarayana, . (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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Official URL: https://doi.org/10.1016/j.fct.2018.06.027

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.

Item Type: Article
Uncontrolled Keywords: Carotenoids Doxorubicin Breast cancer cells Cytotoxicity Oxidative stress-mediated apoptosis
Subjects: Faculty of Science > Environmental and Biological Sciences > Botany
Divisions: Jnana Bharathi / Central College Campus > Department of Botany
Depositing User: Jubeda Begum
Date Deposited: 22 Jul 2019 07:47
Last Modified: 22 Jul 2019 07:47
URI: http://eprints-bangaloreuniversity.in/id/eprint/8802

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