Licochalcone A (LCA) is a chalcone that is predominantly found in the root of Glycyrrhiza species, which is widely used as an herbal medicine. Although previous studies have reported that LCA has a wide range of pharmacological effects, evidence for the underlying molecular mechanism of its anti-cancer efficacy is still lacking. In this study, we investigated the anti-proliferative effect of LCA on human bladder cancer cells, and found that LCA induced cell cycle arrest at G2/M phase and apoptotic cell death. Our data showed that LCA inhibited the expression of cyclin A, cyclin B1, and Wee1, but increased the expression of cyclin-dependent kinase (Cdk) inhibitor p21WAF1/CIP1, and increased p21 was bound to Cdc2 and Cdk2. LCA activated caspase-8 and -9, which are involved in the initiation of extrinsic and intrinsic apoptosis pathways, respectively, and also increased caspase-3 activity, a typical effect caspase, subsequently leading to poly (ADP-ribose) polymerase cleavage. Additionally, LCA increased the Bax/Bcl-2 ratio, and reduced the integrity of mitochondria, which contributed to the discharge of cytochrome c from the mitochondria to the cytoplasm. Moreover, LCA enhanced the intracellular levels of reactive oxygen species (ROS); however, the interruption of ROS generation using ROS scavenger led to escape from LCA-mediated G2/M arrest and apoptosis. Collectively, the present data indicate that LCA can inhibit the proliferation of human bladder cancer cells by inducing ROS-dependent G2/M phase arrest and apoptosis.
International journal of molecular sciences. 2019 Aug 05*** epublish ***
Su Hyun Hong, Hee-Jae Cha, Hyun Hwang-Bo, Min Yeong Kim, So Young Kim, Seon Yeong Ji, JaeHun Cheong, Cheol Park, Hyesook Lee, Gi-Young Kim, Sung-Kwon Moon, Seok Joong Yun, Young-Chae Chang, Wun-Jae Kim, Yung Hyun Choi
Anti-Aging Research Center, Dong-eui University, Busan 47227, Korea., Department of Parasitology and Genetics, Kosin University College of Medicine, Busan 49267, Korea., Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 46241, Korea., Department of Molecular Biology, College of Natural Sciences, Dong-eui University, Busan 47340, Korea., Department of Marine Life Sciences, School of Marine Biomedical Sciences, Jeju National University, Jeju 63243, Korea., Department of Food and Nutrition, Chung-Ang University, Anseong 17546, Korea., Department of Urology, College of Medicine, Chungbuk National University, Chungbuk 8644, Korea., Department of Cell Biology, Catholic University of Daegu School of Medicine, Daegu 42472, Korea., Department of Urology, College of Medicine, Chungbuk National University, Chungbuk 8644, Korea. ., Anti-Aging Research Center, Dong-eui University, Busan 47227, Korea. .