1. Academic Validation
  2. RA and ω-3 PUFA co-treatment activates autophagy in cancer cells

RA and ω-3 PUFA co-treatment activates autophagy in cancer cells

  • Oncotarget. 2017 Nov 22;8(65):109135-109150. doi: 10.18632/oncotarget.22629.
Shenglong Zhu 1 2 3 Guangxiao Lin 1 2 Ci Song 1 2 Yikuan Wu 1 2 Ninghan Feng 3 4 Wei Chen 1 2 5 6 Zhao He 1 2 3 Yong Q Chen 1 2 3 5 7
Affiliations

Affiliations

  • 1 State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China.
  • 2 School of Food Science and Technology, Jiangnan University, Wuxi, China.
  • 3 Wuxi Medical School, Jiangnan University, Wuxi, China.
  • 4 Wuxi No. 2 Hospital, Jiangsu, P. R. China.
  • 5 National Engineer Research Center for Functional Food, Jiangnan University, Wuxi, China.
  • 6 Beijing Innovation Center of Food Nutrition and Human Health, Beijing Technology and Business University, Beijing, China.
  • 7 School of Medicine, Wake Forest University, Winston-Salem, North Carolina, USA.
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 in vitro and in vivo 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.

Keywords

autophagy; breast cancer; retinoic acid; ω-3 PUFAs.

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