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PINK1/Parkin-Mediated Mitophagy Regulation by Reactive Oxygen Species Alleviates Rocaglamide A-Induced Apoptosis in Pancreatic Cancer Cells.


ABSTRACT: Pancreatic cancer (PC) is one of the most lethal diseases, and effective treatment of PC patients remains an enormous challenge. Rocaglamide A (Roc-A), a bioactive molecule extracted from the plant Aglaia elliptifolia, has aroused considerable attention as a therapeutic choice for numerous cancer treatments. Nevertheless, the effects and underlying mechanism of Roc-A in PC are still poorly understood. Here, we found that Roc-A inhibited growth and stimulated apoptosis by induction of mitochondria dysfunction in PC. Moreover, Roc-A accelerated autophagosome synthesis and triggered mitophagy involving the PTEN-induced putative kinase 1 (PINK1)/Parkin signal pathway. We also demonstrated that inhibition of autophagy/mitophagy can sensitize PC cells to Roc-A. Finally, Roc-A treatment results in an obvious accumulation of reactive oxygen species (ROS), and pretreatment of cells with the reactive oxygen species scavenger N-acetylcysteine reversed the apoptosis and autophagy/mitophagy induced by Roc-A. Together, our results elucidate the potential mechanisms of action of Roc-A. Our findings indicate Roc-A as a potential therapeutic agent against PC and suggest that combination inhibition of autophagy/mitophagy may be a promising therapeutic strategy in PC.

SUBMITTER: Zhao C 

PROVIDER: S-EPMC6735223 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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PINK1/Parkin-Mediated Mitophagy Regulation by Reactive Oxygen Species Alleviates Rocaglamide A-Induced Apoptosis in Pancreatic Cancer Cells.

Zhao Chunle C   He Ruizhi R   Shen Ming M   Zhu Feng F   Wang Min M   Liu Yuhui Y   Chen Hua H   Li Xu X   Qin Renyi R  

Frontiers in pharmacology 20190903


Pancreatic cancer (PC) is one of the most lethal diseases, and effective treatment of PC patients remains an enormous challenge. Rocaglamide A (Roc-A), a bioactive molecule extracted from the plant <i>Aglaia elliptifolia</i>, has aroused considerable attention as a therapeutic choice for numerous cancer treatments. Nevertheless, the effects and underlying mechanism of Roc-A in PC are still poorly understood. Here, we found that Roc-A inhibited growth and stimulated apoptosis by induction of mito  ...[more]

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2022-06-29 | GSE203609 | GEO