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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

Effect of IN-2001 on the cyclin D expression. MDA-MB-231 cells were treated with vehicle (0.1% DMSO) or 1 μM IN-2001 for 24 hr. Total RNA was isolated and then subjected to RT-PCR using specific primers. GAPDH served as the loading control. For quantifi cation the band intensity of cyclin D was normalized to that of GAPDH and data was expressed as fold induction compared to control group (p<0.05). *Significantly different from control.
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Figure 007: Effect of IN-2001 on the cyclin D expression. MDA-MB-231 cells were treated with vehicle (0.1% DMSO) or 1 μM IN-2001 for 24 hr. Total RNA was isolated and then subjected to RT-PCR using specific primers. GAPDH served as the loading control. For quantifi cation the band intensity of cyclin D was normalized to that of GAPDH and data was expressed as fold induction compared to control group (p<0.05). *Significantly different from control.

Mentions: As well as cdk inhibitors, one of the important cell cycle regulatoryproteins is cyclin. In this study, we examined the effect of IN-2001 on the expressions of D-type cyclin (cyclin D1 and cyclin D2). MDA-MB-231 cells were treated with vehicle (0.1% DMSO) or 1 μM IN-2001 for 24 hr and then examined for the expression of cyclin D1 and cyclin D2 by RT-PCR analysis. In MDA-MB-231 cells, TSA, HC toxin, and LAQ significantly down-regulated cyclin D1 mRNA level but did not change cyclin D2 mRNA level. Cyclin D2 mRNA level was up-regulated by IN-2001 and SAHA to 1.6-fold and 1.8-fold, respectively (Fig. 7).


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)

Effect of IN-2001 on the cyclin D expression. MDA-MB-231 cells were treated with vehicle (0.1% DMSO) or 1 μM IN-2001 for 24 hr. Total RNA was isolated and then subjected to RT-PCR using specific primers. GAPDH served as the loading control. For quantifi cation the band intensity of cyclin D was normalized to that of GAPDH and data was expressed as fold induction compared to control group (p<0.05). *Significantly different from control.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 007: Effect of IN-2001 on the cyclin D expression. MDA-MB-231 cells were treated with vehicle (0.1% DMSO) or 1 μM IN-2001 for 24 hr. Total RNA was isolated and then subjected to RT-PCR using specific primers. GAPDH served as the loading control. For quantifi cation the band intensity of cyclin D was normalized to that of GAPDH and data was expressed as fold induction compared to control group (p<0.05). *Significantly different from control.
Mentions: As well as cdk inhibitors, one of the important cell cycle regulatoryproteins is cyclin. In this study, we examined the effect of IN-2001 on the expressions of D-type cyclin (cyclin D1 and cyclin D2). MDA-MB-231 cells were treated with vehicle (0.1% DMSO) or 1 μM IN-2001 for 24 hr and then examined for the expression of cyclin D1 and cyclin D2 by RT-PCR analysis. In MDA-MB-231 cells, TSA, HC toxin, and LAQ significantly down-regulated cyclin D1 mRNA level but did not change cyclin D2 mRNA level. Cyclin D2 mRNA level was up-regulated by IN-2001 and SAHA to 1.6-fold and 1.8-fold, respectively (Fig. 7).

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