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. CONCLUSION: 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.
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 humancancer 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. CONCLUSION: 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.
Authors: Ji Hye Park; Mee Young Ahn; Tae Hyung Kim; Sungpill Yoon; Keon Wook Kang; Jaewon Lee; Hyung Ryong Moon; Jee H Jung; Hae Young Chung; Hyung Sik Kim Journal: Invest New Drugs Date: 2011-10-08 Impact factor: 3.850
Authors: Abraham Jacob; Janet Oblinger; Matthew L Bush; Victoria Brendel; Griffin Santarelli; Abhik R Chaudhury; Samuel Kulp; Krista M D La Perle; Ching-Shih Chen; Long-Sheng Chang; D Bradley Welling Journal: Laryngoscope Date: 2011-11-22 Impact factor: 3.325
Authors: Takuhito Narita; Shaoman Yin; Christine F Gelin; Carlos S Moreno; Manuel Yepes; K C Nicolaou; Erwin G Van Meir Journal: Clin Cancer Res Date: 2009-09-29 Impact factor: 12.531
Authors: Kennichi C Dowdell; Lesley Pesnicak; Victoria Hoffmann; Kenneth Steadman; Alan T Remaley; Jeffrey I Cohen; Stephen E Straus; V Koneti Rao Journal: Exp Hematol Date: 2009-02-12 Impact factor: 3.084