Low-dose doxorubicin with carotenoids selectively alters redox status and upregulates oxidative stress-mediated apoptosis in breast cancer cells. (August 2018)

• Record Type: Journal Article
• Authors: Vijay, Kariyappa; Sowmya, Poorigali Raghavendra-Rao; Arathi, Bangalore Prabhashankar; Shilpa, Shivaprasad; Shwetha, Hulikere Jagdish; Raju, Marisiddaiah; Baskaran, Vallikannan; Lakshminarayana, Rangaswamy
• Is Part Of: Food and chemical toxicology. Volume 118(2018)
• Page Start: 675
• Page End: 690
• Publication Date: 2018-08
• Subjects: Carotenoids -- Doxorubicin -- Breast cancer cells -- Cytotoxicity -- Oxidative stress-mediated apoptosis; AST Astaxanthin -- Bcl-2 B-cell lymphoma 2 -- Bax Bcl-2 associated X protein -- BC β-Carotene -- BCA Bicinchoninic acid -- BHT Butylatedhydroxytoluene -- DCF-DA 2′, 7′-Dichlorodihydrofluorescein diacetate -- DMSO Dimethyl sulphoxide -- DOX Doxorubicin -- DTNB 5, 5′-Dithiobis(2-nitrobenzoic acid) -- EDTA Ethylenediaminetetraacetic acid -- FBS Foetal bovine serum -- FUCO Fucoxanthin -- GR Glutathione reductase -- GSH Glutathione -- LDH Lactate dehydrogenase -- LUT Lutein -- LPx Lipid peroxide-malondialdehyde -- MCF-7 MDA-MB-231 Human breast adenocarcinoma cell lines -- MEM Minimum essential medium eagle -- MTT 3-[4, 5-Dimethylthiazol-2-yl]-2, 5- diphenyltetrazolium bromide -- NADPH Nicotinamide adenine dinucleotide phosphate -- p21 Cyclin-dependent kinase inhibitor 1 -- p27 Cyclin-dependent kinase inhibitor 1B -- p53 Phosphoprotein 53 -- PBS Phosphate-buffered saline -- ROS Reactive oxygen species -- THF Tetrahydrofuran; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2018.06.027
• Languages: English
• ISSNs: 0278-6915

Abstract

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. Highlights: ➢ Doxorubicin with carotenoids efficiently inhibits breast cancer cells growth. ➢ Doxorubicin plus carotenoids synergy induced apoptogenic properties in cancer cells. ➢ Selective ROS-mediated apoptosis occurs in doxorubicin with carotenoids treatments. ➢ Differential cytotoxicity of doxorubicin with carotenoids improves cancer therapy.