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

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.

journal_name

Oncol Rep

journal_title

Oncology reports

authors

Yuan SY,Shiau MY,Ou YC,Huang YC,Chen CC,Cheng CL,Chiu KY,Wang SS,Tsai KJ

doi

10.3892/or.2017.5608

subject

Has Abstract

pub_date

2017-06-01 00:00:00

pages

3606-3616

issue

6

eissn

1021-335X

issn

1791-2431

journal_volume

37

pub_type

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