TY - JOUR
T1 - Combination of flavopiridol and embelin effectively inhibit cell growth in hepatocellular carcinoma depending on regulatory relationship between CDK6 and XIAP
AU - Che, Yufang
AU - Zhang, David Y.
AU - Ye, Fei
AU - Wu, Benyan
AU - Jiang, Bo
N1 - Funding Information:
Acknowledgment The authors are grateful for support from the National Science Foundation, China. B Wu, B Jiang conceived the hypothesis and overall study design. Y Che, B Wu, B Jiang, D Zhang, and F Ye participated in the experimental design and Y Che performed all experiments. Y Che and D Zhang summarized the final data. Y Che, B Wu, B Jiang, D Zhang, and F Ye prepared the manuscript.
PY - 2012/11
Y1 - 2012/11
N2 - Flavopiridol, as a cyclin-dependent kinase (CDK) inhibitor, has entered into phase II study of clinical trial in chronic lymphocytic leukemia. In our study, flavopiridol decreased cell viability, significantly arrested cell cycle in G1 phase and induced cell apoptosis in HepG2/ 2.2.1 cells. Flavopiridol also inhibited protein expression of cyclin D1, cyclin-dependent kinase 4 (CDK4), cyclindependent kinase 6 (CDK6), and downregulated X-linked IAP (XIAP) expression in a dose-dependent manner. Further studies using HepG2/2.2.1 cells transfected with CDK6 siRNA or expression vector demonstrated that CDK6 modulates expression of XIAP. Finally, treatment of HepG2/2.2.1 cells with combination of flavopiridol and embelin, as a XIAP specific inhibitor, could inhibit cell proliferation more effectively than each drug alone. Taking together, CDK6 regulates XIAP expression in hepatocellular carcinoma (HCC) cells. Combination of flavopiridol and embelin could be potentially used for HCC treatment subsequently.
AB - Flavopiridol, as a cyclin-dependent kinase (CDK) inhibitor, has entered into phase II study of clinical trial in chronic lymphocytic leukemia. In our study, flavopiridol decreased cell viability, significantly arrested cell cycle in G1 phase and induced cell apoptosis in HepG2/ 2.2.1 cells. Flavopiridol also inhibited protein expression of cyclin D1, cyclin-dependent kinase 4 (CDK4), cyclindependent kinase 6 (CDK6), and downregulated X-linked IAP (XIAP) expression in a dose-dependent manner. Further studies using HepG2/2.2.1 cells transfected with CDK6 siRNA or expression vector demonstrated that CDK6 modulates expression of XIAP. Finally, treatment of HepG2/2.2.1 cells with combination of flavopiridol and embelin, as a XIAP specific inhibitor, could inhibit cell proliferation more effectively than each drug alone. Taking together, CDK6 regulates XIAP expression in hepatocellular carcinoma (HCC) cells. Combination of flavopiridol and embelin could be potentially used for HCC treatment subsequently.
KW - CDK6
KW - Embelin
KW - Flavopiridol
KW - Hepatocellular carcinoma
KW - XIAP
UR - http://www.scopus.com/inward/record.url?scp=84871428427&partnerID=8YFLogxK
U2 - 10.1007/s00044-011-9867-y
DO - 10.1007/s00044-011-9867-y
M3 - Article
AN - SCOPUS:84871428427
SN - 1054-2523
VL - 21
SP - 3369
EP - 3375
JO - Medicinal Chemistry Research
JF - Medicinal Chemistry Research
IS - 11
ER -