BA-j as a novel CDK1 inhibitor selectively induces apoptosis in cancer cells by regulating ROS

Scientific Reports
Shixuan ZhangQingyu Fan

Abstract

Cyclin-dependent kinase 1 (CDK1) is the only necessary CDK in cell proliferation and a novel target in the development of anticancer drugs. 8-Hydroxypiperidinemethyl-baicalein (BA-j) is a novel selective CDK1 inhibitor with broad spectrum anti-cancer activity (IC50 12.3 μM) and 2 tumor xenografts. Because of the differential mechanisms controlling redox-states in normal and cancer cells, BA-j can capture oxygen free radicals ((·)O2(-)) and selectively increase the level of H2O2 in cancer cells, thereby specifically oxidize and activate the intrinsic apoptosis pathway bypassing the extrinsic death receptor pathway, thus inducing apoptosis in cancer cells rather than in normal cells. BA-j is different from cytotoxic anticancer drugs which can activate both the intrinsic apoptosis pathway and the extrinsic death receptor pathway, and therefore harm normal cells while killing cancer cells. The molecular and biochemical mechanisms of reactive oxygen species (ROS) regulation suggest that BA-j may be developed into a novel anticancer agent.

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Citations

May 7, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Shuiling JinWei Jiang
Mar 21, 2019·Evidence-based Complementary and Alternative Medicine : ECAM·Chongyang MaFafeng Cheng
Jun 27, 2018·Journal of Experimental & Clinical Cancer Research : CR·Rodrigo Prieto-BermejoÁngel Hernández-Hernández
May 25, 2021·Journal of Food Biochemistry·Jasmine BabyLekshmi R Nath

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Methods Mentioned

BETA
xenograft
xenografts
flow cytometry
FRET
ELISA
density gradient centrifugation

Software Mentioned

ModFit LT
Quantity One

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