Ponicidin suppresses HT29 cell growth via the induction of G1 cell cycle arrest and apoptosis.

Abstract

Ponicidin is a diterpenoid extracted from the Chinese herb Isodon adenolomus, which has been reported as a therapeutic cytotoxic drug that may be used to treat various types of human cancer. The present study aimed to determine the antitumor effects of ponicidin, and to investigate its underlying mechanisms in colorectal cancer. The HT29 colorectal cancer cell line was used to detect the cytotoxicity of various doses of ponicidin. Cell proliferation was measured using a Cell Counting kit‑8 assay. Cell cycle and apoptosis analyses were performed using flow cytometry and fluorescent microscopy. Western blot analysis was used to measure the expression levels of apoptosis‑associated proteins following treatment with ponicidin. Treatment with ponicidin significantly suppressed HT29 cell growth by inducing G1 cell cycle arrest and apoptosis. The AKT and MEK signaling pathways were also suppressed by ponicidin; however, the p38 signaling pathway was significantly activated. The expression levels of caspase 3 and Bax protein were markedly upregulated following treatment with ponicidin. These results suggest that ponicidin exerts significant antitumor effects via the induction of cell cycle arrest and apoptosis in colorectal cells. In conclusion, ponicidin acted as an inducer of apoptosis, and may be used as a therapeutic cytotoxic drug to treat human cancer, including colorectal cancer.

• Authors: Jie Du, Chunyou Chen, Yiqun Sun, Lin Zheng, Wanchen Wang
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 12 Issue 4 Pg. 5816-20 (Oct 2015) ISSN: 1791-3004 [Electronic] Greece
• PMID: 26239027 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents, Phytogenic
• Diterpenes
• bcl-2-Associated X Protein
• ponicidin
• Proto-Oncogene Proteins c-akt
• p38 Mitogen-Activated Protein Kinases
• MAP Kinase Kinase Kinases
• Caspase 3

Topics

• Antineoplastic Agents, Phytogenic (pharmacology)
• Apoptosis (drug effects)
• Caspase 3 (genetics, metabolism)
• Cell Proliferation (drug effects)
• Diterpenes (pharmacology)
• Dose-Response Relationship, Drug
• G1 Phase Cell Cycle Checkpoints (drug effects)
• Gene Expression Regulation, Neoplastic
• HT29 Cells
• Humans
• MAP Kinase Kinase Kinases (antagonists & inhibitors, genetics, metabolism)
• Proto-Oncogene Proteins c-akt (antagonists & inhibitors, genetics, metabolism)
• Signal Transduction
• bcl-2-Associated X Protein (agonists, genetics, metabolism)
• p38 Mitogen-Activated Protein Kinases (genetics, metabolism)