The natural product peiminine represses colorectal carcinoma tumor growth by inducing autophagic cell death.

Abstract

Autophagy is evolutionarily conservative in eukaryotic cells that engulf cellular long-lived proteins and organelles, and it degrades the contents through fusion with lysosomes, via which the cell acquires recycled building blocks for the synthesis of new molecules. In this study, we revealed that peiminine induces cell death and enhances autophagic flux in colorectal carcinoma HCT-116 cells. We determined that peiminine enhances the autophagic flux by repressing the phosphorylation of mTOR through inhibiting upstream signals. Knocking down ATG5 greatly reduced the peiminine-induced cell death in wild-type HCT-116 cells, while treating Bax/Bak-deficient cells with peiminine resulted in significant cell death. In summary, our discoveries demonstrated that peiminine represses colorectal carcinoma cell proliferation and cell growth by inducing autophagic cell death.

• Authors: Qing Lyu, Fangfang Tou, Hong Su, Xiaoyong Wu, Xinyi Chen, Zhi Zheng
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 462 Issue 1 Pg. 38-45 (Jun 19 2015) ISSN: 1090-2104 [Electronic] United States
• PMID: 25935480 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Biological Products
• Cevanes
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases
• AMP-Activated Protein Kinases
• peiminine

Topics

• AMP-Activated Protein Kinases (metabolism)
• Animals
• Autophagy (drug effects)
• Biological Products (chemistry, pharmacology)
• Cevanes (chemistry, pharmacology)
• Colorectal Neoplasms (metabolism, pathology, prevention & control)
• Dose-Response Relationship, Drug
• Female
• HCT116 Cells
• HeLa Cells
• Humans
• Immunoblotting
• Immunohistochemistry
• Mice, Inbred BALB C
• Mice, Nude
• Microscopy, Confocal
• Molecular Structure
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphorylation
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction (drug effects)
• TOR Serine-Threonine Kinases (metabolism)
• Tumor Burden (drug effects)
• Xenograft Model Antitumor Assays