[Inhibition of curcumin on histone deacetylase and expression promotion of P21 (WAF1/CIP1) in HepG2 cells].
OBJECTIVE
To investigate the effect of curcumin (Cur) on histone deacetylase (HDAC1) and P21(WAF1/CIP1), a cyclin dependent kinase inhibitor, in HepG2 cells for exploring the mechanism of Cur in anti-cancer.


METHODS
The HDAC1, P21(WAF1/CIP1) proteins and P21(WAF1/CIP1) mRNA were extracted from human hepatoma cells treated with or without Cur of different concentrations at different time points. Western blot analysis was performed to determine the levels of HDAC1 and P21(WAF1/CIP1) proteins, respectively. RT-PCR was performed to detect the level of P21(WAF1/CIP1) mRNA.


RESULTS
The IC50 of concentration treated by Cur was 25 micromol x L(1) on HepG2 cell. The level of HDAC1 was obviously inhibited by Cur, and decreased at 4 hours at IC, and lasted for 48 h in a time-dependent manner. The inhibition of HDAC1 was significant at the Cur concentration of 12.5 micromol x L(-1) but there was no difference between 50 and 100 micromol x L(-1). The levels of P21(WAF1/CIP1) mRNA and protein were up-regulated by Cur in dose and time-dependent manner, and the change of mRNA and protein was detected at 8 hours and lasted for 48 hours.


CONCLUSIONS
Cur can inhibit the level of HDAC1 and enhance the expression of P21(WAF1/CIP1) protein and mRNA, and the results suggest that inhibiting HDAC1 and increasing P21(WAF1/CIP1) may be one of the possible mechanisms of anti-cancer by Cur.
Lv
Bi-Hua
BH
Zhongnan Hospital, Wuhan University, Wuhan 430071, China.
Zhang
Ling
L
Zhu
Chang-Cai
CC
Liu
Jing
J
D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D030024:Curcuma / Q000737:chemistry; D003474:Curcumin / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010946:Plants, Medicinal / Q000737:chemistry; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D056572:Histone Deacetylase Inhibitors; D012333:RNA, Messenger; D006655:Histone Deacetylases; D003474:Curcumin