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Inhibitory effect of protein arginine methyltransferase 1 inhibitor DB75 on bladder cancer T24 cells(PDF)

Chinese Journal of Applied & Environmental Biology[ISSN:1006-687X/CN:51-1482/Q]

2015 01
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Inhibitory effect of protein arginine methyltransferase 1 inhibitor DB75 on bladder cancer T24 cells
ZENG Zhongqiu MA Yuling PEI Zhe CHEN Yuwen WANG Jing TANG Yaxiong
Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China
bladder cancer PRMT1 DB75 apoptosis
R965 : R979.1

Protein arginine methyltransferase 1 (PRMT1), as a newly discovered epigenetic modified enzyme, is overexpressed in many cancers including bladder cancer and plays a crucial role in malignant transformation. Therefore, PRMT1 may be a novel valuable therapeutic target for cancer chemoprevention. In our study, DB75 was identified as a PRMT1 inhibitor by using the pharmacophore-based virtual screening system, and the antitumor potential and molecular mechanism of DB75 were further evaluated in vitro. The experimental results showed that DB75 signi?cantly suppressed the proliferation of bladder cancer T24 cells in a dose-dependent manner, with the IC50 value as 2.2 μmol/L after 48 h exposure to DB75. In addition, DB75 induced apoptosis in T24 cells. Altogether, DB75 could activate Caspase-3 and PARP activity, and lead to marked apoptotic effect on bladder cancer T24 cells. Together, these ?ndings suggested that DB75 may be a promising epigenetic lead compound for prevention and treatment of bladder cancer.


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