British Journal of Pharmacology p. 2008 - 2027 (2010)
Update date:2022-08-11
Topics:
Shen, Cheng-Huang
Shee, Jia-Jen
Wu, Jin-Yi
Lin, Yi-Wen
Wu, Jiann-Der
Liu, Yi-Wen
BACKGROUND AND PURPOSE Bladder cancer is a highly recurrent cancer after intravesical therapy, so new drugs are needed to treat this cancer. Hence, we investigated the anti-cancer activity of combretastatin A-4 (CA-4), an anti-tubulin agent, in human bladder cancer cells and in a murine orthotopic bladder tumour model. EXPERIMENTAL APPROACH Cytotoxicity of CA-4 was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, propidium iodide (PI) staining assay and clonogenic survival assay. In vivo microtubule assembly assay, cell cycle analyses, Western blot and cell migration assay were used to study the mechanism of CA-4. The effect of intravesical CA-4 therapy on the development of tumours was studied in the murine orthotopic bladder tumour model. KEY RESULTS CA-4 inhibited microtubule polymerization in vivo. Cytotoxic IC50 values of CA-4 in human bladder cancer cells were below 4 nM. Analyses of cell-cycle distribution showed CA-4 obviously induced G2-M phase arrest with sub-G1 formation. The analyses of apoptosis showed that CA-4 induced caspase-3 activation and decreased BubR1 and Bub3 in cancer cells. In addition to apoptosis, CA-4 was also found to induce the formation of multinucleated cells. CA-4 had a significantly reduced cell migration in vitro. Importantly, the in vivo study revealed that intravesical CA-4 therapy retarded the development of murine bladder tumours. CONCLUSIONS AND IMPLICATIONS These data demonstrate that CA-4 kills bladder cancer cells by inducing apoptosis and mitotic catastrophe. It inhibited cell migration in vitro and tumour growth in vivo. Hence, CA-4 intravesical therapy could provide another strategy for treating superficial bladder cancers.
View MoreZhejiang Chemicals Import & Export Corporation
Contact:86-571-87043088
Address:No.37,Qingchun Road,Hangzhou,China
Changzhou Hopschain Chemical Co.,Ltd
Contact:86-519-85528066
Address:Room 710, Unit A, Xingbei Development Mansion, Tongjiang Road, Changzhou City,213000, China
WUHAN CHEMPROSPECT PHARMTECH CO., LTD
website:http://www.chemprospect.com
Contact:+86--27-84984898
Address:No. 2, Road, East Lake Hi-tech Development Zone, Wuhan, China
website:http://www.orchid-chem.com
Contact:+86-571-85395792
Address:607, North Zhongshan Road, Hangzhou 310000 China
Contact:
Address:ROOM 1715, No#345 Jin Xiang Road, Pudong District
Doi:10.1021/ja00271a022
(1986)Doi:10.1007/BF00849345
()Doi:10.1039/c2jm33818a
(2012)Doi:10.1016/j.bioorg.2020.104469
(2021)Doi:10.1002/9780470132357.ch14
(1953)Doi:10.3390/molecules25071642
(2020)