Anti-tumor effect of apicidin on Ishikawa human endometrial cancer cells both in vitro and in vivo by blocking histone deacetylase 3 and 4.
Histone deacetylase (HDAC) inhibitors are a new class of anticancer agents that act by inhibiting cancer cell proliferation and inducing apoptosis both in vitro and in vivo. This study examined the anti-tumor effect of apicidin on human endometrial cancer Ishikawa cells in an animal model by inhibiting specific HDAC expression. Nude mice were injected subcutaneously (s.c.) with Ishikawa cells, and the levels of cell proliferation and apoptosis were measured in the tumor tissues after an apicidin treatment. The expression patterns of a specific HDAC class by apicidin were measured in Ishikawa endometrial cancer both in vitro and in vivo. The tumor volume and weight were measured after the apicidin treatment. Apicidin significantly increased the acetylated histone H3 levels in an Ishikawa cells in vitro culture but the levels of HDAC3 and HDAC4 expression were significantly decreased. Apicidin suppressed the tumor growth of transplanted Ishikawa cells, the expression of proliferative cell nuclear antigen (PCNA) and vascular endothelial growth factor (VEGF) in tumor xenograft model, respectively. The inhibitory effect of apicidin on tumor growth was mediated in part through the down-regulation of HDAC3 and HDAC4. We suggest that apicidin is an effective anti-tumor agent on human endometrial cancer cells, and acts by regulating cell proliferation and apoptosis through the down-regulation of HDAC3 and HDAC4.
Ahn
Mee Young
MY
College of Pharmacy, Pusan National University, San 30, Jangjeon-dong, Geumjeung-gu, Busan 609-735, Korea.
Chung
Hae Young
HY
Choi
Wahn Soo
WS
Lee
Byung Mu
BM
Yoon
Sungpil
S
Kim
Hyung Sik
HS
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D016889:Endometrial Neoplasms / Q000378:metabolism*; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000737:chemistry*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010456:Peptides, Cyclic / Q000494:pharmacology*; D012097:Repressor Proteins / Q000737:chemistry*; D000099186:Histone Deacetylase 3
D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; D010456:Peptides, Cyclic; D012097:Repressor Proteins; D000099186:Histone Deacetylase 3; C102351:apicidin; C400300:HDAC4 protein, human