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Open AccessArticle

Flavopereirine Inhibits Autophagy via the AKT/p38 MAPK Signaling Pathway in MDA-MB-231 Cells

Department of Anesthesiology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi 60002, Taiwan
Department of Biotechnology, Asia University, Taichung 41354, Taiwan
Department of Medical Research, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi 60002, Taiwan
Department of Medical Laboratory Science and Biotechnology, Chung Hwa University of Medical Technology, Tainan 71703, Taiwan
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(15), 5362;
Received: 12 June 2020 / Revised: 30 June 2020 / Accepted: 23 July 2020 / Published: 28 July 2020
(This article belongs to the Special Issue Autophagy in Health, Ageing and Disease 2.0)
Autophagy is a potential target for the treatment of triple negative breast cancer (TNBC). Because of a lack of targeted therapies for TNBC, it is vital to find optimal agents that avoid chemoresistance and metastasis. Flavopereirine has anti-proliferation ability in cancer cells, but whether it regulates autophagy in breast cancer cells remains unclear. A Premo™ Tandem Autophagy Sensor Kit was used to image the stage at which flavopereirine affects autophagy by confocal microscopy. A plasmid that constitutively expresses p-AKT and siRNA targeting p38 mitogen-activated protein kinase (MAPK) was used to confirm the related signaling pathways by Western blot. We found that flavopereirine induced microtubule-associated protein 1 light chain 3 (LC3)-II accumulation in a dose- and time-dependent manner in MDA-MB-231 cells. Confocal florescent images showed that flavopereirine blocked autophagosome fusion with lysosomes. Western blotting showed that flavopereirine directly suppressed p-AKT levels and mammalian target of rapamycin (mTOR) translation. Recovery of AKT phosphorylation decreased the level of p-p38 MAPK and LC3-II, but not mTOR. Moreover, flavopereirine-induced LC3-II accumulation was partially reduced in MDA-MB-231 cells that were transfected with p38 MAPK siRNA. Overall, flavopereirine blocked autophagy via LC3-II accumulation in autophagosomes, which was mediated by the AKT/p38 MAPK signaling pathway. View Full-Text
Keywords: flavopereirine; autophagy; breast cancer; AKT; p38 MAPK flavopereirine; autophagy; breast cancer; AKT; p38 MAPK
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Chen, M.-S.; Yeh, H.-T.; Li, Y.-Z.; Lin, W.-C.; Lee, Y.-R.; Tseng, Y.-S.; Sheu, S.-M. Flavopereirine Inhibits Autophagy via the AKT/p38 MAPK Signaling Pathway in MDA-MB-231 Cells. Int. J. Mol. Sci. 2020, 21, 5362.

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