Journal of Cancer Research and Clinical Oncology

, Volume 138, Issue 10, pp 1743–1751

Guggulsterone enhances antitumor activity of gemcitabine in gallbladder cancer cells through suppression of NF-κB

  • Moon Hee Yang
  • Kyu Taek Lee
  • Sera Yang
  • Jong Kyoon Lee
  • Kwang Hyuck Lee
  • Il Hwan Moon
  • Jong Chul Rhee
Original Paper

DOI: 10.1007/s00432-012-1254-7

Cite this article as:
Yang, M.H., Lee, K.T., Yang, S. et al. J Cancer Res Clin Oncol (2012) 138: 1743. doi:10.1007/s00432-012-1254-7

Abstract

Purpose

Patients with gallbladder cancer usually have a poor prognosis, and effective standard chemotherapeutic regimens have not been established. The anticancer activities of guggulsterone have been demonstrated in various cancer cells. The aims of the study were to determine the effect of guggulsterone on gallbladder cancer cells and to investigate whether treatment with guggulsterone influences the antitumor activities of gemcitabine.

Methods

The Dojindo Cell Counting Kit-8 assay was used to determine the inhibition of proliferation by drugs in TGBC1 and TGBC2 cells. Cell migration and invasion were examined using 24-well inserts and Matrigel™-coated invasion chambers. The activities of NF-κB p65, VEGF-C, and MMP-2 were measured by ELISA.

Results

Guggulsterone inhibited the proliferation and suppressed migration and invasion of gallbladder cancer cells in a dose-dependent manner. Guggulsterone significantly decreased NF-κB p65, VEGF-C, and MMP-2 activities in the gallbladder cancer cells examined. Gallbladder cancer cells treated with a combination of guggulsterone and gemcitabine demonstrated significant inhibition of cell proliferation and invasion when compared to treatment with gemcitabine alone. In addition, NF-κB p65 activation decreased significantly in cells treated with a combination of guggulsterone and gemcitabine when compared to treatment with gemcitabine alone.

Conclusions

Guggulsterone exhibits anticancer activities and enhances the antitumor activities of gemcitabine through the suppression of NF-κB activation in gallbladder cancer cells. These results suggest that guggulsterone could be a potential therapeutic option for patients with gallbladder cancer.

Keywords

Gallbladder cancer Guggulsterone Gemcitabine NF-κB 

Abbreviations

GBC

Gallbladder cancer

GS

Guggulsterone

FXR

Farnesoid X receptor

NF-κB

Nuclear factor-kappa B

VEGF-C

Vascular endothelial growth factor-C

MMP-2

Matrix metalloproteinase-2

DMEM

Dulbecco’s modified Eagle’s medium

FBS

Fetal bovine serum

MEM

Minimum essential medium

DMSO

Dimethylsulphoxide

SEM

The standard error of the mean

BTC

Biliary tract cancer

IκB

Inhibitor of κB

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Moon Hee Yang
    • 1
  • Kyu Taek Lee
    • 2
  • Sera Yang
    • 3
  • Jong Kyoon Lee
    • 2
  • Kwang Hyuck Lee
    • 2
  • Il Hwan Moon
    • 4
  • Jong Chul Rhee
    • 2
  1. 1.Center for Health Promotion, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea
  2. 2.Department of Medicine, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea
  3. 3.Samsung Biomedical Research Institute, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea
  4. 4.Department of MedicineEwha Woman’s University Mokdong HospitalSeoulKorea

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