Low-dose doxorubicin with carotenoids selectively alters redox status and upregulates oxidative stress-mediated apoptosis in breast cancer cells.
IR@CFTRI: CSIR-Central Food Technological Research Institute, Mysore
View Archive Info| Field | Value | |
| Relation |
http://ir.cftri.com/13838/
https://doi.org/10.1016/j.fct.2018.06.027 |
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| Title |
Low-dose doxorubicin with carotenoids selectively alters redox status and
upregulates oxidative stress-mediated apoptosis in breast cancer cells.
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| Creator |
Vijay, K.
Sowmya, P. R. Rao Arathi, B. P. Baskaran, V. |
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| Subject |
14 Carotenoid Chemistry
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| Description |
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.
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| Date |
2018
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| Type |
Article
PeerReviewed |
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| Format |
pdf
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| Language |
en
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| Identifier |
http://ir.cftri.com/13838/1/Food%20and%20Chemical%20Toxicology%20118%20%282018%29%20675%E2%80%93690.pdf
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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