1. Glaucocalyxin A induces G2/M cell cycle arrest and apoptosis through the PI3K/Akt pathway in human bladder cancer cells
- Author
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Yubo Gao, Jinlin Xie, Peng Huang, Chunxiao Liu, Hulin Li, Naijin Xu, Masami Watanabe, Linglong Huang, Wenfeng Lin, Abai Xu, and Chaoming Li
- Subjects
0301 basic medicine ,Mice, SCID ,Applied Microbiology and Biotechnology ,Phosphatidylinositol 3-Kinases ,03 medical and health sciences ,0302 clinical medicine ,Mice, Inbred NOD ,Cell Line, Tumor ,Animals ,Humans ,PTEN ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,PI3K/AKT/mTOR pathway ,Cell Proliferation ,Cyclin-dependent kinase 1 ,biology ,Cell growth ,Chemistry ,Akt/PKB signaling pathway ,apoptosis ,PTEN Phosphohydrolase ,Cell Cycle Checkpoints ,Cell Biology ,Cell cycle ,Glaucocalyxin A ,G2 Phase Cell Cycle Checkpoints ,030104 developmental biology ,Urinary Bladder Neoplasms ,PI3K/Akt pathway ,Apoptosis ,030220 oncology & carcinogenesis ,Cancer cell ,Cancer research ,biology.protein ,bladder cancer ,cell cycle ,Female ,Diterpenes, Kaurane ,Proto-Oncogene Proteins c-akt ,Research Paper ,Signal Transduction ,Developmental Biology - Abstract
Glaucocalyxin A (GLA), a major component isolated from Rabdosia japonica, has been proven to show anti-bacterial and anti-tumor biological characteristics according to previous studies. However, its potential effect on bladder cancer remains unknown. The present research aims to investigate the underlying mechanism in treating bladder cancer in vivo and in vitro. Cell proliferation was analyzed by CCK-8 assay and colony formation. Flow cytometry was used to measure the cell cycle distribution and apoptosis. The expressions of the cell cycle and apoptosis-related proteins were detected by western blotting and immunofluorescence staining. Meanwhile, the in vivo study was performed to evaluate the anti-tumor effect on a UMUC3 subcutaneous tumor of NOD/SCID mice model. GLA suppressed colony-formation ability, triggered G2/M arrest and promoted apoptosis of UMUC3 cells in a dose-dependent manner. Furthermore, western blotting showed that GLA downregulated the expressions of PI3K p85, p-Akt, Bcl-2, CDK1, Cyclin B1 whereas upregulated the levels of PTEN, Bax, Cleaved Caspase-3. In vivo, GLA at a dosage of 20 mg/kg significantly inhibited tumor growth compared with the control group by intraperitoneal injection. These results suggested that GLA-related G2/M arrest and apoptosis in UMUC3 cells were mediated by a suppressed PI3K/Akt signaling pathway, which regulated p21Waf1/Cip1 as well as intrinsic caspase cascade. Collectively, our observations could help to develop new drugs targeting the PI3K/Akt pathway for the treatment of bladder cancer.
- Published
- 2018