Abstract

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.

Original languageEnglish
Pages (from-to)136-143
Number of pages8
JournalToxicology
Volume223
Issue number1-2
DOIs
Publication statusPublished - Jun 1 2006

Fingerprint

Cantharidin
Cyclooxygenase 2
Cytotoxicity
Urinary Bladder
Cells
Carcinoma
Cell Line
Caspase 3
HT29 Cells
Cystitis
G2 Phase
Cell Division
Necrosis
Apoptosis
Cyclin B1
Cyclin A
Caspase Inhibitors
Poisons
Cell death
Dinoprostone

Keywords

  • Cantharidin
  • Chinese blister beetle (Mylabris phalerata Pallas)
  • Cyclooxygenase 2
  • Cystitis
  • Cytotoxicity
  • Inflammation

ASJC Scopus subject areas

  • Toxicology

Cite this

Cantharidin-induced cytotoxicity and cyclooxygenase 2 expression in human bladder carcinoma cell line. / Huan, Steven Kuan Hua; Lee, Hao Hsien; Liu, Der Zen; Wu, Chien Chih; Wang, Ching Chiung.

In: Toxicology, Vol. 223, No. 1-2, 01.06.2006, p. 136-143.

Research output: Contribution to journalArticle

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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

PY - 2006/6/1

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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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