Alpha-mangostin induces endoplasmic reticulum stress and autophagy which count against fatty acid synthase inhibition mediated apoptosis in human breast cancer cells

Cancer Cell International

Wenyuan Huang¹  Xiaofeng Ma¹  Yan Liang² 

[1] College of Life Sciences, University of Chinese Academy of Sciences;School of Kinesiology and Health, Capital University of Physical Education and Sports;

关键词: Fatty acid synthase;    Alpha-mangostin;    Inhibitor;    Autophagy;    Endoplasmic reticulum stress;   

DOI  :  10.1186/s12935-019-0869-z

来源: DOAJ

【 摘 要 】

Abstract Background/aims One of the most important metabolic hallmarks of breast cancer cells is enhanced lipogenesis. Increasing evidences suggest that fatty acid synthase (FAS) plays an important role in human breast cancer. Previously we discovered that alpha-mangostin showed apoptotic effect on human breast cancer cells via inhibiting FAS activity. The endoplasmic reticulum (ER) stress and autophagy are involved in cell apoptosis. However, the role of ER stress and autophagy in FAS inhibition induced apoptosis still remains unclear. Methods We evaluated the effects of alpha-mangostin on ER stress and autophagy in human breast cancer cells. Intracellular FAS activity was measured by a spectrophotometer at 340 nm of NADPH absorption. Cell Counting Kit assay was used to test the cell viability. Immunoblot analysis was performed to detect protein expression levels. Apoptotic effects were detected by flow cytometry. Results Alpha-mangostin induced endoplasmic reticulum stress and autophagy, both of which reduced the apoptotic effect of alpha-mangostin in MDA-MB-231 cells. Palmitic acid, the end product of FAS catalyzed reaction, rescued the ER stress and autophagy induced by alpha-mangostin. Cell apoptosis was markedly promoted by inhibiting ER stress and autophagy while treating cells with alpha-mangostin. Conclusion We propose a hypothesis that a combination of FAS inhibition and ER stress and autophagy inhibition has an application potential in the chemoprevention and treatment of breast cancer.

【 授权许可】

Unknown