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 μmol/L dose-dependently suppressed COLO 205 cell proliferation by MTT test. Row cytometry analysis and DNA fragmentation assay revealed that 10-20 μmol/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.

Original languageEnglish
Pages (from-to)3040-3045
Number of pages6
JournalWorld Journal of Gastroenterology
Volume11
Issue number20
Publication statusPublished - May 28 2005

Fingerprint

Colonic Neoplasms
Carcinogenesis
Apoptosis Inducing Factor
Apoptosis
Caspase 8
Heterografts
Nude Mice
Neoplasms
BH3 Interacting Domain Death Agonist Protein
denbinobin
Caspase 9
Mitogen-Activated Protein Kinase Kinases
Extracellular Signal-Regulated MAP Kinases
DNA Fragmentation
Cytochromes c
Caspase 3
Signal Transduction
Western Blotting
Cell Proliferation
Cell Line

Keywords

  • Apoptosis
  • Colon cancer
  • Denbinobin
  • ERK pathway
  • Nude mice

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Molecular mechanisms of denbinobin-induced anti-tumorigenesis effect in colon cancer cells. / Yang, Kuo-Ching; Uen, Yih Huei; Suk, Fat Moon; Liang, Yu Chih; Wang, Ying Jan; Ho, Yuan Soon; Li, I. Hsuan; Lin, Shyr Yi.

In: World Journal of Gastroenterology, Vol. 11, No. 20, 28.05.2005, p. 3040-3045.

Research output: Contribution to journalArticle

@article{67f1809650e74a2bae23c60b22ce444f,
title = "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 μmol/L dose-dependently suppressed COLO 205 cell proliferation by MTT test. Row cytometry analysis and DNA fragmentation assay revealed that 10-20 μmol/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.",
keywords = "Apoptosis, Colon cancer, Denbinobin, ERK pathway, Nude mice",
author = "Kuo-Ching Yang and Uen, {Yih Huei} and Suk, {Fat Moon} and Liang, {Yu Chih} and Wang, {Ying Jan} and Ho, {Yuan Soon} and Li, {I. Hsuan} and Lin, {Shyr Yi}",
year = "2005",
month = "5",
day = "28",
language = "English",
volume = "11",
pages = "3040--3045",
journal = "World Journal of Gastroenterology",
issn = "1007-9327",
publisher = "WJG Press",
number = "20",

}

TY - JOUR

T1 - Molecular mechanisms of denbinobin-induced anti-tumorigenesis effect in colon cancer cells

AU - Yang, Kuo-Ching

AU - Uen, Yih Huei

AU - Suk, Fat Moon

AU - Liang, Yu Chih

AU - Wang, Ying Jan

AU - Ho, Yuan Soon

AU - Li, I. Hsuan

AU - Lin, Shyr Yi

PY - 2005/5/28

Y1 - 2005/5/28

N2 - 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 μmol/L dose-dependently suppressed COLO 205 cell proliferation by MTT test. Row cytometry analysis and DNA fragmentation assay revealed that 10-20 μmol/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.

AB - 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 μmol/L dose-dependently suppressed COLO 205 cell proliferation by MTT test. Row cytometry analysis and DNA fragmentation assay revealed that 10-20 μmol/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.

KW - Apoptosis

KW - Colon cancer

KW - Denbinobin

KW - ERK pathway

KW - Nude mice

UR - http://www.scopus.com/inward/record.url?scp=20344391974&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=20344391974&partnerID=8YFLogxK

M3 - Article

VL - 11

SP - 3040

EP - 3045

JO - World Journal of Gastroenterology

JF - World Journal of Gastroenterology

SN - 1007-9327

IS - 20

ER -