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

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

  • Front Pharmacol. 2019 Sep 3;10:968. doi: 10.3389/fphar.2019.00968.
Chunle Zhao 1 Ruizhi He 1 Ming Shen 1 Feng Zhu 1 Min Wang 1 Yuhui Liu 1 Hua Chen 1 Xu Li 1 Renyi Qin 1
Affiliations

Affiliation

  • 1 Laboratory of Biliary-Pancreatic Surgery, Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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.

Keywords

apoptosis; mitophagy; pancreatic cancer; reactive oxygen species; rocaglamide A.

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