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.
School of Life Sciences, Tsinghua University, Beijing, 100084, PR China; Key Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, PR China.
Qing
Q
Lyu
Jiangxi Provincial Key Lab of Oncology Translation Medicine, Jiangxi Cancer Hospital, Nanchang, 330029, PR China.
Fangfang
F
Tou
First Affiliated Hospital, Guiyang College of Traditional Chinese Medicine, Guiyang, 550002, PR China.
Hong
H
Su
First Affiliated Hospital, Guiyang College of Traditional Chinese Medicine, Guiyang, 550002, PR China.
Xiaoyong
X
Wu
Department of Hematology and Oncology, Beijing University of Chinese Medicine, Beijing, 100029, PR China.
Xinyi
X
Chen
Jiangxi Provincial Key Lab of Oncology Translation Medicine, Jiangxi Cancer Hospital, Nanchang, 330029, PR China. Electronic address: zheng_sheva@hotmail.com.
Zhi
Z
Zheng
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology*; D002595:Cevanes / Q000737:chemistry / Q000494:pharmacology*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005260:Female; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018613:Microscopy, Confocal; D015394:Molecular Structure; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D055372:AMP-Activated Protein Kinases; D001688:Biological Products; D002595:Cevanes; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C047331:peiminine
Autophagic cell death; Autophagy; Natural product; Peiminine