TY - JOUR
T1 - Cantharidin-induced cytotoxicity and cyclooxygenase 2 expression in human bladder carcinoma cell line
AU - Huan, Steven Kuan Hua
AU - Lee, Hao Hsien
AU - Liu, Der Zen
AU - Wu, Chien Chih
AU - Wang, Ching Chiung
N1 - Funding Information:
This work was supported by grants from Chi-Mei Medical Center, Tainan, Taiwan (grant nos. CMFHR9349 and CMFHR 9327) and Topnotch Stroke Research Center grant, Ministry of Education.
PY - 2006/6/1
Y1 - 2006/6/1
N2 - Mylabris is used in clinical therapy, but is always accompanied by cystitis. The toxic effects of mylabris on bladder are attributed to its active principle: cantharidin. In the present study, we explored how cantharidin induces cytotoxicity in the bladder. Human bladder carcinoma cell line T 24 cells were used as target cells, and human colon carcinoma HT 29 cells as native cells. Cantharidin exhibited acute cytotoxicity in the T 24 cells, and IC50 was 21.8, 11.2 and 4.6 μM after treatment for 6, 24 and 48 h, respectively. The cytotoxicity of cantharidin was not significantly enhanced when T 24 cells were treated for a longer time. Moreover, PARP proteins and pro-caspase 3, Bcl-2 were significantly inhibited after cantharidin treatment in T 24 cells. Pretreatment with the caspase 3 inhibitor markedly inhibited cantharidin-induced cell death. Therefore, we suggested that cantharidin could induce apoptosis via active caspase 3 in T 24 cells. When T 24 cells were treated with cantharidin at a low dose, the cell cycle was arrested in the G2/M phase. Furthermore, p21Cip1/Waf1 was enhanced, and cyclin A, B1 and cdk1 decreased. At a high dose (more 12.5 μM), cantharidin could stimulate T 24 cells to deplete a large number of ATP and induce secondary necrosis. In addition, cantharidin also stimulated COX 2 over-expression and PGE2 production in T 24 cells, in a dose-dependent manner. However, cantharidin also induced apoptosis and G2/M phase arrest in HT 29 cells, but did not induce COX 2 over-expression. Therefore, we suggest that cantharidin may induce cystitis through secondary necrosis and COX 2 over-expression.
AB - Mylabris is used in clinical therapy, but is always accompanied by cystitis. The toxic effects of mylabris on bladder are attributed to its active principle: cantharidin. In the present study, we explored how cantharidin induces cytotoxicity in the bladder. Human bladder carcinoma cell line T 24 cells were used as target cells, and human colon carcinoma HT 29 cells as native cells. Cantharidin exhibited acute cytotoxicity in the T 24 cells, and IC50 was 21.8, 11.2 and 4.6 μM after treatment for 6, 24 and 48 h, respectively. The cytotoxicity of cantharidin was not significantly enhanced when T 24 cells were treated for a longer time. Moreover, PARP proteins and pro-caspase 3, Bcl-2 were significantly inhibited after cantharidin treatment in T 24 cells. Pretreatment with the caspase 3 inhibitor markedly inhibited cantharidin-induced cell death. Therefore, we suggested that cantharidin could induce apoptosis via active caspase 3 in T 24 cells. When T 24 cells were treated with cantharidin at a low dose, the cell cycle was arrested in the G2/M phase. Furthermore, p21Cip1/Waf1 was enhanced, and cyclin A, B1 and cdk1 decreased. At a high dose (more 12.5 μM), cantharidin could stimulate T 24 cells to deplete a large number of ATP and induce secondary necrosis. In addition, cantharidin also stimulated COX 2 over-expression and PGE2 production in T 24 cells, in a dose-dependent manner. However, cantharidin also induced apoptosis and G2/M phase arrest in HT 29 cells, but did not induce COX 2 over-expression. Therefore, we suggest that cantharidin may induce cystitis through secondary necrosis and COX 2 over-expression.
KW - Cantharidin
KW - Chinese blister beetle (Mylabris phalerata Pallas)
KW - Cyclooxygenase 2
KW - Cystitis
KW - Cytotoxicity
KW - Inflammation
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U2 - 10.1016/j.tox.2006.03.012
DO - 10.1016/j.tox.2006.03.012
M3 - Article
C2 - 16697099
AN - SCOPUS:33646751454
SN - 0300-483X
VL - 223
SP - 136
EP - 143
JO - Toxicology
JF - Toxicology
IS - 1-2
ER -