Desethylamiodarone—A metabolite of amiodarone—Induces apoptosis on T24 human bladder cancer cells via multiple pathways

Z. Bognár, Katalin Fekete, Csenge Antus, Eniko Hocsak, Rita Bognar, Antal Tapodi, A. Boronkai, Nelli Farkas, F. Gallyas, B. Sümegi, Arpad Szanto

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Bladder cancer (BC) is a common malignancy of the urinary tract that has a higher frequency in men than in women. Cytostatic resistance and metastasis formation are significant risk factors in BC therapy; therefore, there is great interest in overcoming drug resistance and in initiating research for novel chemotherapeutic approaches. Here, we suggest that desethylamiodarone (DEA)–a metabolite of amiodarone—may have cytostatic potential. DEA activates the collapse of mitochondrial membrane potential (detected by JC-1 fluorescence), and induces cell death in T24 human transitional-cell bladder carcinoma cell line at physiologically achievable concentrations. DEA induces cell cycle arrest in the G0/G1 phase, which may contribute to the inhibition of cell proliferation, and shifts the Bax/ Bcl-2 ratio to initiate apoptosis, induce AIF nuclear translocation, and activate PARP-1 cleavage and caspase-3 activation. The major cytoprotective kinases—ERK and Akt—are inhibited by DEA, which may contribute to its cell death-inducing effects. DEA also inhibits the expression of B-cell-specific Moloney murine leukemia virus integration site 1 (BMI1) and reduces colony formation of T24 bladder carcinoma cells, indicating its possible inhibitory effect on metastatic potential. These data show that DEA is a novel anti-cancer candidate of multiple cell death-inducing effects and metastatic potential. Our findings recommend further evaluation of its effects in clinical studies.

Original languageEnglish
Article numbere0189470
JournalPLoS One
Volume12
Issue number12
DOIs
Publication statusPublished - Dec 1 2017

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Metabolites
Urinary Bladder Neoplasms
cell death
apoptosis
Cells
Apoptosis
metabolites
bladder
carcinoma
Cell death
Murine leukemia virus
Cell Death
urinary tract
drug resistance
Cytostatic Agents
caspase-3
membrane potential
metastasis
interphase
B-lymphocytes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Desethylamiodarone—A metabolite of amiodarone—Induces apoptosis on T24 human bladder cancer cells via multiple pathways. / Bognár, Z.; Fekete, Katalin; Antus, Csenge; Hocsak, Eniko; Bognar, Rita; Tapodi, Antal; Boronkai, A.; Farkas, Nelli; Gallyas, F.; Sümegi, B.; Szanto, Arpad.

In: PLoS One, Vol. 12, No. 12, e0189470, 01.12.2017.

Research output: Contribution to journalArticle

Bognár, Z. ; Fekete, Katalin ; Antus, Csenge ; Hocsak, Eniko ; Bognar, Rita ; Tapodi, Antal ; Boronkai, A. ; Farkas, Nelli ; Gallyas, F. ; Sümegi, B. ; Szanto, Arpad. / Desethylamiodarone—A metabolite of amiodarone—Induces apoptosis on T24 human bladder cancer cells via multiple pathways. In: PLoS One. 2017 ; Vol. 12, No. 12.
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