Toosendanin inhibits growth and induces apoptosis in colorectal cancer cells through suppression of AKT/GSK-3β/β-catenin pathway.

Abstract

AKT/GSK-3β/β-catenin signaling pathway plays an important role in the progression of colorectal cancer (CRC). Toosendanin (TSN) is a triterpenoid extracted from the bark or fruits of Melia toosendan Sieb et Zucc and possesses antitumour effects on various human cancer cells. However, its effect on CRC remains poorly understood. The present study investigated the effect of TSN on CRC SW480 cells and the AKT/GSK-3β/β-catenin signaling. Proliferation assay, flow cytometry and Hoechst 33342 nuclear staining demonstrated TSN dose-dependently inhibited cell viability and induced cell apoptosis as well as cell cycle arrest in S phase. Confocal laser scanning microscope showed β-catenin transferred to the outside of the nucleus in TSN-treated cells. Quantitative real-time PCR and western blot analysis found that TSN effectively modulated molecules related to apoptosis and AKT/GSK-3β/β-catenin signaling. Moreover, TSN administration significantly inhibited CRC growth in a mouse tumor xenograft model. In conclusion, our findings indicate that TSN inhibits growth and induces apoptosis in CRC cells through suppression of AKT/GSK-3β/β-catenin pathway, suggesting that TSN may have potential for use in CRC treatment.

• Authors: Ge Wang, Cheng-Cheng Feng, Shao-Jun Chu, Rui Zhang, Yun-Min Lu, Jin-Shui Zhu, Jing Zhang
• Journal: International journal of oncology (Int J Oncol) Vol. 47 Issue 5 Pg. 1767-74 (Nov 2015) ISSN: 1791-2423 [Electronic] Greece
• PMID: 26398368 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Drugs, Chinese Herbal
• beta Catenin
• toosendanin
• GSK3B protein, human
• Glycogen Synthase Kinase 3 beta
• Gsk3b protein, mouse
• Oncogene Protein v-akt
• Glycogen Synthase Kinase 3

Topics

• Animals
• Apoptosis (drug effects)
• Cell Cycle Checkpoints (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Colorectal Neoplasms (drug therapy, genetics, pathology)
• Drugs, Chinese Herbal (administration & dosage)
• Glycogen Synthase Kinase 3 (genetics)
• Glycogen Synthase Kinase 3 beta
• Humans
• Mice
• Oncogene Protein v-akt (genetics)
• Signal Transduction (drug effects)
• beta Catenin (genetics)