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Triazole-dithiocarbamate based selective lysine specific demethylase 1 (LSD1) inactivators inhibit gastric cancer cell growth, invasion, and migration.


ABSTRACT: Lysine specific demethylase 1 (LSD1), the first identified histone demethylase, plays an important role in epigenetic regulation of gene activation and repression. The up-regulated LSD1's expression has been reported in several malignant tumors. In the current study, we designed and synthesized five series of 1,2,3-triazole-dithiocarbamate hybrids and screened their inhibitory activity toward LSD1. We found that some of these compounds, especially compound 26, exhibited the most specific and robust inhibition of LSD1. Interestingly, compound 26 also showed potent and selective cytotoxicity against LSD1 overexpressing gastric cancer cell lines MGC-803 and HGC-27, as well as marked inhibition of cell migration and invasion, compared to 2-PCPA. Furthermore, compound 26 effectively reduced the tumor growth bared by human gastric cancer cells in vivo with no signs of adverse side effects. These findings suggested that compound 26 deserves further investigation as a lead compound in the treatment of LSD1 overexpressing gastric cancer.

SUBMITTER: Zheng YC 

PROVIDER: S-EPMC3881423 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Triazole-dithiocarbamate based selective lysine specific demethylase 1 (LSD1) inactivators inhibit gastric cancer cell growth, invasion, and migration.

Zheng Yi-Chao YC   Duan Ying-Chao YC   Ma Jin-Lian JL   Xu Rui-Min RM   Zi Xiaolin X   Lv Wen-Lei WL   Wang Meng-Meng MM   Ye Xian-Wei XW   Zhu Shun S   Mobley David D   Zhu Yan-Yan YY   Wang Jun-Wei JW   Li Jin-Feng JF   Wang Zhi-Ru ZR   Zhao Wen W   Liu Hong-Min HM  

Journal of medicinal chemistry 20131101 21


Lysine specific demethylase 1 (LSD1), the first identified histone demethylase, plays an important role in epigenetic regulation of gene activation and repression. The up-regulated LSD1's expression has been reported in several malignant tumors. In the current study, we designed and synthesized five series of 1,2,3-triazole-dithiocarbamate hybrids and screened their inhibitory activity toward LSD1. We found that some of these compounds, especially compound 26, exhibited the most specific and rob  ...[more]

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