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


CONCLUSIONS
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.
Yang
Kuo-Ching
KC
Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, China.
Uen
Yih-Huei
YH
Suk
Fat-Moon
FM
Liang
Yu-Chih
YC
Wang
Ying-Jan
YJ
Ho
Yuan-Soon
YS
Li
I-Hsuan
IH
Lin
Shyr-Yi
SY
D000818:Animals; D000880:Anthraquinones / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D010616:Phenanthrenes / Q000627:therapeutic use*; D014183:Transplantation, Heterologous
D000880:Anthraquinones; D000970:Antineoplastic Agents; D010616:Phenanthrenes; C436544:denbinobin