Molecular mechanisms of denbinobin-induced anti-tumorigenesis effect in colon cancer cells.

Abstract

AIM:

To explore both the in vitro and in vivo effects of denbinobin against colon cancer cells and clarify its underlying signal pathways.

METHODS:

We used COLO 205 cancer cell lines and nude mice xenograft model to study the in vitro and in vivo anti-cancer effects of denbinobin.

RESULTS:

Denbinobin at concentration of 10-20 micromol/L dose-dependently suppressed COLO 205 cell proliferation by MTT test. Flow cytometry analysis and DNA fragmentation assay revealed that 10-20 micromol/L denbinobin treatment induced COLO 205 cells apoptosis. Western blot analysis showed that caspases 3, 8, 9 and Bid protein were activated by denbinobin treatment to COLO 205 cells accompanied with cytochrome c and apoptosis-inducing factor (AIF) translocation. Pretreatment of MEK 1 inhibitor (U10126), but not p38 inhibitor (SB203580) and JNK inhibitor (SP600125), reversed denbinobin-induced caspase 8, 9 and Bid activation in COLO 205 cells suggesting that extracellular signal-regulated kinase were involved in the denbinobin-induced apoptosis in COLO 205 cells. Significant regression of tumor up to 68% was further demonstrated in vivo by treating nude mice bearing COLO 205 tumor xenografts with denbinobin 50 mg/kg intraperitoneally.

CONCLUSION:

Our findings suggest that denbinobin could inhibit colon cancer growth both in vitro and in vivo. Activation of extrinsic and intrinsic apoptotic pathways and AIF were involved in the denbinobin-induced COLO 205 cell apoptosis.

• Authors: Kuo-Ching Yang, Yih-Huei Uen, Fat-Moon Suk, Yu-Chih Liang, Ying-Jan Wang, Yuan-Soon Ho, I-Hsuan Li, Shyr-Yi Lin
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 11 Issue 20 Pg. 3040-5 (May 28 2005) ISSN: 1007-9327 [Print] United States
• PMID: 15918186 (Publication Type: Journal Article)

Chemical References

• Anthraquinones
• Antineoplastic Agents
• Phenanthrenes
• denbinobin

Topics

• Animals
• Anthraquinones (therapeutic use)
• Antineoplastic Agents (therapeutic use)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Colonic Neoplasms (drug therapy, pathology)
• Mice
• Mice, Nude
• Phenanthrenes (therapeutic use)
• Transplantation, Heterologous