BA-j as a novel CDK1 inhibitor selectively induces apoptosis in cancer cells by regulating ROS.
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.
State Key Laboratory of Fine Chemicals, School of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian, Liaoning, China.
Shixuan
S
Zhang
School of Bioscience and Technology, Dalian University of Technology, Dalian, Liaoning, China.
Yongming
Y
Bao
College of Vocational and Technical, Dalian University, Dalian, Liaoning, China.
Xiulan
X
Ju
State Key Laboratory of Fine Chemicals, School of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian, Liaoning, China.
Kangjian
K
Li
School of Bioscience and Technology, Dalian University of Technology, Dalian, Liaoning, China.
Haiyan
H
Shang
State Key Laboratory of Fine Chemicals, School of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian, Liaoning, China.
Lisha
L
Ha
State Key Laboratory of Fine Chemicals, School of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian, Liaoning, China.
Yuan
Y
Qian
State Key Laboratory of Fine Chemicals, School of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian, Liaoning, China.
Liang
L
Zou
State Key Laboratory of Fine Chemicals, School of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian, Liaoning, China.
Xiaodan
X
Sun
State Key Laboratory of Fine Chemicals, School of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian, Liaoning, China.
Jing
J
Li
State Key Laboratory of Fine Chemicals, School of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian, Liaoning, China.
Qianru
Q
Wang
State Key Laboratory of Fine Chemicals, School of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian, Liaoning, China.
Qingyu
Q
Fan
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D053222:Fas Ligand Protein / Q000378:metabolism; D047309:Flavones / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008251:Macaca; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
C000606484:8-hydroxypiperidinylmethylbaicalein; D000970:Antineoplastic Agents; D053222:Fas Ligand Protein; D047309:Flavones; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D017382:Reactive Oxygen Species; D016203:CDC2 Protein Kinase; D000111:Acetylcysteine