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Anti-Cancer Effect of IN-2001 in MDA-MB-231 Human Breast Cancer.

Min KN, Joung KE, Kim DK, Sheen YY - Biomol Ther (Seoul) (2012)

Bottom Line: But their precise mechanism of action has not been elucidated.These events are accompanied by modulating several cell cycle and apoptosis regulatory genes such as CDK inhibitors p21(WAF1) and p27(KIP1) cyclin D1, and other tumor suppressor genes such as cyclin D2.In summary, our data suggest that this histone deacetylase inhibitor, IN-2001, is a novel promising therapeutic agent with potent antitumor effects against human breast cancers.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Ewha Womans University, Seoul 120-750, Republic of Korea.

ABSTRACT
In recent years, inhibition of HDACs has emerged as a potential strategy to reverse aberrant epigenetic changes associated with cancer, and several classes of HDAC inhibitors have been found to have potent and specific anticancer activities in preclinical studies. But their precise mechanism of action has not been elucidated. In this study, a novel synthetic inhibitor of HDAC, 3-(4-dimethylamino phenyl)-N-hydroxy-2-propenamide [IN-2001] was examined for its antitumor activity and the underlying molecular mechanisms of any such activity on human breast cancer cell lines. IN-2001 effectively inhibited cellular HDAC activity (IC50 = 0.585 nM) in MDA-MB-231 human breast cancer cells. IN-2001 caused a significant dose-dependent inhibition of cell proliferation in estrogen receptor (ER) negative MDA-MB-231 human breast cancer cells. Cell cycle analysis revealed that the gowth inhibitory effects of IN-2001 might be attributed to cell cycle arrest at G0/G1 and/or G2/Mphase and subsequent apoptosis in human breast cancer cells. These events are accompanied by modulating several cell cycle and apoptosis regulatory genes such as CDK inhibitors p21(WAF1) and p27(KIP1) cyclin D1, and other tumor suppressor genes such as cyclin D2. Collectively, IN-2001 inhibited cell proliferation and induced apoptosis in human breast cancer cells and these findings may provide new therapeutic approaches, combination of antiestrogen together with a HDAC inhibitor, in the hormonal therapy-resistant ER-negative breast cancers. In summary, our data suggest that this histone deacetylase inhibitor, IN-2001, is a novel promising therapeutic agent with potent antitumor effects against human breast cancers.

No MeSH data available.


Related in: MedlinePlus

Time-dependent growth inhibition by IN-2001. Human breast cancer MDA-MB-231 cells were treated with vehicle (0.1% DMSO) or 1 μM IN-2001 for various exposure time (0-72 hr). The number of cells was determined by SRB assay and cell proliferation was expressed as percent of control. Data present mean ± S.D. (N=4).
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Figure 003: Time-dependent growth inhibition by IN-2001. Human breast cancer MDA-MB-231 cells were treated with vehicle (0.1% DMSO) or 1 μM IN-2001 for various exposure time (0-72 hr). The number of cells was determined by SRB assay and cell proliferation was expressed as percent of control. Data present mean ± S.D. (N=4).

Mentions: In the next experiment, we carried out time-course experiment with 1 μM IN-2001. As shown in Fig. 3, IN-2001 decreased the proliferation of MDA-MB-231 human breast cancer cells in a time-dependent manner. MDA-MB-231 cells


Anti-Cancer Effect of IN-2001 in MDA-MB-231 Human Breast Cancer.

Min KN, Joung KE, Kim DK, Sheen YY - Biomol Ther (Seoul) (2012)

Time-dependent growth inhibition by IN-2001. Human breast cancer MDA-MB-231 cells were treated with vehicle (0.1% DMSO) or 1 μM IN-2001 for various exposure time (0-72 hr). The number of cells was determined by SRB assay and cell proliferation was expressed as percent of control. Data present mean ± S.D. (N=4).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3794529&req=5

Figure 003: Time-dependent growth inhibition by IN-2001. Human breast cancer MDA-MB-231 cells were treated with vehicle (0.1% DMSO) or 1 μM IN-2001 for various exposure time (0-72 hr). The number of cells was determined by SRB assay and cell proliferation was expressed as percent of control. Data present mean ± S.D. (N=4).
Mentions: In the next experiment, we carried out time-course experiment with 1 μM IN-2001. As shown in Fig. 3, IN-2001 decreased the proliferation of MDA-MB-231 human breast cancer cells in a time-dependent manner. MDA-MB-231 cells

Bottom Line: But their precise mechanism of action has not been elucidated.These events are accompanied by modulating several cell cycle and apoptosis regulatory genes such as CDK inhibitors p21(WAF1) and p27(KIP1) cyclin D1, and other tumor suppressor genes such as cyclin D2.In summary, our data suggest that this histone deacetylase inhibitor, IN-2001, is a novel promising therapeutic agent with potent antitumor effects against human breast cancers.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Ewha Womans University, Seoul 120-750, Republic of Korea.

ABSTRACT
In recent years, inhibition of HDACs has emerged as a potential strategy to reverse aberrant epigenetic changes associated with cancer, and several classes of HDAC inhibitors have been found to have potent and specific anticancer activities in preclinical studies. But their precise mechanism of action has not been elucidated. In this study, a novel synthetic inhibitor of HDAC, 3-(4-dimethylamino phenyl)-N-hydroxy-2-propenamide [IN-2001] was examined for its antitumor activity and the underlying molecular mechanisms of any such activity on human breast cancer cell lines. IN-2001 effectively inhibited cellular HDAC activity (IC50 = 0.585 nM) in MDA-MB-231 human breast cancer cells. IN-2001 caused a significant dose-dependent inhibition of cell proliferation in estrogen receptor (ER) negative MDA-MB-231 human breast cancer cells. Cell cycle analysis revealed that the gowth inhibitory effects of IN-2001 might be attributed to cell cycle arrest at G0/G1 and/or G2/Mphase and subsequent apoptosis in human breast cancer cells. These events are accompanied by modulating several cell cycle and apoptosis regulatory genes such as CDK inhibitors p21(WAF1) and p27(KIP1) cyclin D1, and other tumor suppressor genes such as cyclin D2. Collectively, IN-2001 inhibited cell proliferation and induced apoptosis in human breast cancer cells and these findings may provide new therapeutic approaches, combination of antiestrogen together with a HDAC inhibitor, in the hormonal therapy-resistant ER-negative breast cancers. In summary, our data suggest that this histone deacetylase inhibitor, IN-2001, is a novel promising therapeutic agent with potent antitumor effects against human breast cancers.

No MeSH data available.


Related in: MedlinePlus