Miconazole induces apoptosis via the death receptor 5-dependent and mitochondrial-mediated pathways in human bladder cancer cells

Yuan,Sheau-Yun; Shiau,Ming-Yuh; Ou,Yen-Chuan; Huang,Yu-Chia; Chen,Cheng-Che; Cheng,Chen-Li; Chiu,Kun-Yuan; Wang,Shian-Shiang; Tsai,Kan-Jen

doi:10.3892/or.2017.5608

Miconazole induces apoptosis via the death receptor 5-dependent and mitochondrial-mediated pathways in human bladder cancer cells

Authors:
- Sheau-Yun Yuan
- Ming-Yuh Shiau
- Yen-Chuan Ou
- Yu-Chia Huang
- Cheng-Che Chen
- Chen-Li Cheng
- Kun-Yuan Chiu
- Shian-Shiang Wang
- Kan-Jen Tsai
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Affiliations: Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung 40705, Taiwan, R.O.C., Department of Nursing, Hung Kung University, Taichung 43302, Taiwan, R.O.C., Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung 40201, Taiwan, R.O.C.
Published online on: April 27, 2017 https://doi.org/10.3892/or.2017.5608
Pages: 3606-3616

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Abstract

Miconazole (MIC), an antifungal agent, diplays anti‑tumorigenic activity in various types of human cancers, including bladder cancer, yet its mechanism of antitumor action is not well understood. In the present study, we demonstrated that, in a cell viability assay, MIC had a cytotoxic effect on human T24, J82 and TSGH-8301 bladder cancer cells in a dose- and time‑dependent manner, but did not exhibit significant toxicity toward human peripheral blood mononuclear cells. Cell cycle analysis revealed that MIC at concentrations of 25 and 50 µM significantly caused G0/G1 arrest in the TSGH-8301 and T24 cells, respectively. DNA fragmentation, mitochondrial membrane potential and western blot analyses showed that MIC inhibited the growth of these cells by both mitochondrial‑mediated and death receptor (DR5)‑mediated apoptosis pathways. Specifically, MIC increased the protein levels of p21 and p27, but decreased the expression of cyclin E1, CDK2 and CDK4. MIC augmented the expression of DR5, cleaved forms of caspase-3 -8 and -9, poly(ADP‑ribose) polymerase and Bax, decreased the expression of Bcl-2 but increased cytosol levels of cytochrome c. Our results suggest that MIC inhibits the growth of bladder cancer cells through induction of G0/G1 arrest and apoptosis via activation of both the extrinsic and intrinsic apoptotic pathways. MIC is a potential chemotherapeutic agent for treating bladder cancer in humans.

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