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

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. - Highlights: • Peiminine induces autophagy and upregulates autophagic flux. • Peiminine represses colorectal carcinoma tumor growth. • Peiminine induces autophagic cell death. • Peiminine represses mTOR phosphorylation by influencing PI3K/Akt and AMPK pathway.
Authors:
 [1] ;  [2] ;  [3] ; ;  [4] ;  [5] ;  [3]
  1. School of Life Sciences, Tsinghua University, Beijing, 100084 (China)
  2. (China)
  3. Jiangxi Provincial Key Lab of Oncology Translation Medicine, Jiangxi Cancer Hospital, Nanchang, 330029 (China)
  4. First Affiliated Hospital, Guiyang College of Traditional Chinese Medicine, Guiyang, 550002 (China)
  5. Department of Hematology and Oncology, Beijing University of Chinese Medicine, Beijing, 100029 (China)
Publication Date:
OSTI Identifier:
22462087
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 462; Journal Issue: 1; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; CARCINOMAS; CELL CONSTITUENTS; CELL PROLIFERATION; LYSOSOMES; PHOSPHORYLATION; PLANT GROWTH; PROTEINS; SYNTHESIS