Apicidin Induces Apoptosis via Cytochrome c-Mediated Intrinsic Pathway in Human Ovarian Cancer Cells

Ahn, Mee Young; Na, Yong Jin; Lee, Jaewon; Lee, Byung Mu; Kim, Hyung Sik

doi:10.4062/biomolther.2009.17.1.17

Cited by 9 publications

(4 citation statements)

References 24 publications

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“…Previously, it was suggested apicidin inhibits the proliferation of a variety of human cancer cell lines including SK-OV-3 and Ishikawa cells (18,19). In order to confirm apicidin-induced cytotoxicity on endometrial cancer cells, the cells were treated with varying doses of the drug for 24, 48 or 72 h, and the cell viability was measured using an MTT assay.…”

Section: Resultsmentioning

confidence: 99%

Anti-tumor effect of apicidin on Ishikawa human endometrial cancer cells both in vitro and in vivo by blocking histone deacetylase 3 and 4

Kim

2009

Int J Oncol

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Abstract. 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.

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Section: Resultsmentioning

confidence: 99%

Anti-tumor effect of apicidin on Ishikawa human endometrial cancer cells both in vitro and in vivo by blocking histone deacetylase 3 and 4

Kim

2009

Int J Oncol

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“…3). One of well-known phenomena of apoptosis is the activation of caspases (Ahn et al, 2009). Ochnaflavone-mediated apoptosis seems to be explained the consequential activation of caspase-8, -9 and caspase-3 and thus induces the cleavage of PARP, a target protein of caspases.…”

Section: Discussionmentioning

confidence: 99%

Ochnaflavone, a Natural Biflavonoid, Induces Cell Cycle Arrest and Apoptosis in HCT-15 Human Colon Cancer Cells

Kang¹,

Min²,

Hong³

et al. 2009

Biomolecules and Therapeutics

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-Ochnaflavone is a natural biflavonoid and mainly found in the caulis of Lonicera japonica (Caprifoliaceae). Biological activities such as anti-inflammatory and anti-atherogenic effects have been previously reported. The anticancer activity of ochnaflavone, however, has been poorly elucidated yet. In the present study, we investigated the effect of ochnaflavone on the growth inhibitory activity in cultured human colon cancer cell line HCT-15. Ochnaflavone inhibited the proliferation of the cancer cells with an IC 50 value of 4.1 μM. Flow cytometric analysis showed that ochnaflavone arrested cell cycle progression in the G2/M phase, and induced the increase of sub-G1 peak in a concentration-dependent manner. Induction of cell cycle arrest was correlated with the modulation of the expression of cell cycle regulating proteins including cdc2 (Tyr15), cyclin A, cyclin B1 and cyclin E. The increase of sub-G1 peak by the higher concentrations of ochnaflavone (over 20 μM) was closely related to the induction of apoptosis, which was evidenced by the induction of DNA fragmentation, activation of caspase-3, -8 and -9, and cleavage of poly-(ADP-ribose) polymerase. These findings suggest that the cell cycle arrest and induction of apoptosis might be one possible mechanism of actions for the anti-proliferative activity of ochnaflavone in human colon cancer cells.

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“…Conversion of procaspase 3 to the effector protease was observed with concomitant cleavage of poly(ADP-ribose) polymerase, a downstream effect of the activation of caspase 9 [155, 156]. Cytochrome C was released in the cytosol and correlated with the onset of apoptosis and activation of caspase 3 in response to apicidin treatment [155]. In vivo testing of apicidin using human endometrial cancer cells implanted in BALB/C mice showed a significant reduction in tumor growth compared to control group [157].…”

Section: Biological Effects Of Histone Acetylation Modulatorsmentioning

confidence: 99%

Discovery and Mechanism of Natural Products as Modulators of Histone Acetylation

Salvador¹,

Luesch²

2012

CDT

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Small molecules that modulate histone acetylation by targeting key enzymes mediating this posttranslational modification – histone acetyltransferases and histone deacetylases – are validated chemotherapeutic agents for the treatment of cancer. This area of research has seen a rapid increase in interest in the past decade, with the structurally diverse natural products-derived compounds at its forefront. These secondary metabolites from various biological sources target this epigenetic modification through distinct mechanisms of enzyme regulation by utilizing a diverse array of pharmacophores. We review the discovery of these compounds and discuss their modes of inhibition together with their downstream biological effects.

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Apicidin Induces Apoptosis via Cytochrome c-Mediated Intrinsic Pathway in Human Ovarian Cancer Cells

Cited by 9 publications

References 24 publications

Anti-tumor effect of apicidin on Ishikawa human endometrial cancer cells both in vitro and in vivo by blocking histone deacetylase 3 and 4

Anti-tumor effect of apicidin on Ishikawa human endometrial cancer cells both in vitro and in vivo by blocking histone deacetylase 3 and 4

Ochnaflavone, a Natural Biflavonoid, Induces Cell Cycle Arrest and Apoptosis in HCT-15 Human Colon Cancer Cells

Discovery and Mechanism of Natural Products as Modulators of Histone Acetylation

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