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Open AccessArticle

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

1
Department of Anesthesiology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi 60002, Taiwan
2
Department of Biotechnology, Asia University, Taichung 41354, Taiwan
3
Department of Medical Research, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi 60002, Taiwan
4
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; https://doi.org/10.3390/ijms21155362
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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