A natural histone deacetylase inhibitor, Psammaplin A, induces cell cycle arrest and apoptosis in human endometrial cancer cells.
OBJECTIVE
Histone deacetylase (HDAC) inhibitors are promising new class of anticancer agents that act by inhibiting cell proliferation and inducing cell cycle arrest of various cancer cells. Psammaplin A (PsA) is a phenolic natural product that has been isolated from marine sponges, and has been suggested to be a promising novel HDAC inhibitor. However, the precise mechanism of PsA as a HDAC inhibitor is poorly understood. This study investigated the anti-tumor effect of PsA on endometrial human cancer cells.


METHODS
The cell proliferation, cell cycle, and apoptosis were measured in Ishikawa endometrial cancer cells after PsA treatment.


RESULTS
PsA significantly inhibited the proliferation of Ishikawa cells in a dose-dependent manner. PsA markedly induced the expression of acetylated H3 and H4 histone proteins. In addition, PsA markedly up-regulated the expression of cyclin-dependent kinase inhibitor, p21(WAF1), and down-regulated the expression of pRb, cyclins, and CDKs, which lead to induce cell cycle arrest. Cell cycle analysis indicated that PsA treatment increased the proportion of cells in the G0/G1 and G2/M phases, and decreased the ratio of cells in the S phase.


CONCLUSIONS
The PsA treatment resulted in the significant induction of apoptosis, which was associated with p53 independent p21(WAF1) expression. These results suggest that PsA exhibits the antiproliferative effects on endometrial cancer cells through selective induction of genes related to cell cycle arrest and apoptosis.
Ahn
Mee Young
MY
College of Pharmacy, Pusan National University, San 30, Jangjeon-dong, Geumjung-gu, Busan 609-735, Republic of Korea.
Jung
Jee H
JH
Na
Yong Jin
YJ
Kim
Hyung Sik
HS
D000107:Acetylation / Q000187:drug effects; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D045744:Cell Line, Tumor; D004220:Disulfides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D056572:Histone Deacetylase Inhibitors; D006657:Histones / Q000378:metabolism; D006801:Humans; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D004220:Disulfides; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; C098378:psammaplin A; D014443:Tyrosine