RA and ω-3 PUFA Co-treatment Activates Autophagy in Cancer Cells

Overview

Journal Oncotarget

Specialty Oncology

Date 2018 Jan 10

PMID 29312596

Citations 8

Authors

Shenglong Zhu

Guangxiao Lin

Ci Song

Yikuan Wu

Ninghan Feng

Wei Chen

Zhao He

Yong Q Chen

Affiliations

Soon will be listed here.

Abstract

Retinoic acid (RA), is a promising therapeutic agent for the treatment of breast cancer. However, metabolic disorders and drug resistance reduce the efficacy of RA. In this study, we found that RA and ω-3 polyunsaturated fatty acids (ω-3 PUFAs) synergistically induced cell death and and autophagy activation. Moreover, RA-induced hypercholesterolemia was completely corrected by ω-3 PUFA supplementation. In addition, we demonstrated that the effects of this combination on the autophagic flux were independent of the two major canonic regulatory complexes controlling autophagic vesicle formation. The treatment activated Gαq-p38 MAPK signaling pathways, which resulted in autophagy of breast cancer cells. Knockdown of Gαq or P38 expression prevented RA and ω-3 PUFAs from inducing autophagy. Data indicated that Gαq-p38activation was mediated by the co-activation of GPR40 and RARα in lipid rafts, rather than by the activation of GPR120, RARβ, or RARγ. The results of this study suggest that hyperlipidemic drug side effects may be ameliorated by the administration of ω-3 PUFAs. Thus, the therapeutic indexes of the corresponding drugs may be increased.

Citing Articles

Retraction Note: ω-3 free fatty acids and all-trans retinoic acid synergistically induce growth inhibition of three subtypes of breast cancer cell lines.

Lin G, Zhu S, Wu Y, Song C, Wang W, Zhang Y Sci Rep. 2024; 14(1):26769.

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The Effects of Omega-3 Polyunsaturated Fatty Acids on Breast Cancer as a Preventive Measure or as an Adjunct to Conventional Treatments.

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PA and OA induce abnormal glucose metabolism by inhibiting KLF15 in adipocytes.

Wang C, Chu X, Deng Y, Wang J, Qiu T, Zhu J Nutr Metab (Lond). 2021; 18(1):100.

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