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Activation of BK(Ca) Channels in Zoledronic Acid-Induced Apoptosis of MDA-MB-231 Breast Cancer Cells

BACKGROUND: Zoledronic acid, one of the most potent nitrogen-containing biphosphonates, has been demonstrated to have direct anti-tumor and anti-metastatic properties in breast cancer in vitro and in vivo. In particular, tumor-cell apoptosis has been recognized to play an important role in the treat...

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Autores principales: Ma, Yu-Guang, Liu, Wen-Chao, Dong, Shuo, Du, Cheng, Wang, Xiao-Jun, Li, Jin-Sheng, Xie, Xiao-Ping, Wu, Li, Ma, Da-Chang, Yu, Zhi-Bin, Xie, Man-Jiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3360057/
https://www.ncbi.nlm.nih.gov/pubmed/22655048
http://dx.doi.org/10.1371/journal.pone.0037451
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author Ma, Yu-Guang
Liu, Wen-Chao
Dong, Shuo
Du, Cheng
Wang, Xiao-Jun
Li, Jin-Sheng
Xie, Xiao-Ping
Wu, Li
Ma, Da-Chang
Yu, Zhi-Bin
Xie, Man-Jiang
author_facet Ma, Yu-Guang
Liu, Wen-Chao
Dong, Shuo
Du, Cheng
Wang, Xiao-Jun
Li, Jin-Sheng
Xie, Xiao-Ping
Wu, Li
Ma, Da-Chang
Yu, Zhi-Bin
Xie, Man-Jiang
author_sort Ma, Yu-Guang
collection PubMed
description BACKGROUND: Zoledronic acid, one of the most potent nitrogen-containing biphosphonates, has been demonstrated to have direct anti-tumor and anti-metastatic properties in breast cancer in vitro and in vivo. In particular, tumor-cell apoptosis has been recognized to play an important role in the treatment of metastatic breast cancer with zoledronic acid. However, the precise mechanisms remain less clear. In the present study, we investigated the specific role of large conductance Ca(2+)-activated potassium (BK(Ca)) channel in zoledronic acid-induced apoptosis of estrogen receptor (ER)-negative MDA-MB-231 breast cancer cells. METHODOLOGY/PRINCIPAL FINDINGS: The action of zoledronic acid on BK(Ca) channel was investigated by whole-cell and cell-attached patch clamp techniques. Cell apoptosis was assessed with immunocytochemistry, analysis of fragmented DNA by agarose gel electrophoresis, and flow cytometry assays. Cell proliferation was investigated by MTT test and immunocytochemistry. In addition, such findings were further confirmed with human embryonic kidney 293 (HEK293) cells which were transfected with functional BK(Ca) α-subunit (hSloα). Our results clearly indicated that zoledronic acid directly increased the activities of BK(Ca) channels, and then activation of BK(Ca) channel by zoledronic acid contributed to induce apoptosis in MDA-MB-231 cells. The possible mechanisms were associated with the elevated level of intracellular Ca(2+) and a concomitant depolarization of mitochondrial membrane potential (Δψm) in MDA-MB-231 cells. CONCLUSIONS: Activation of BK(Ca) channel was here shown to be a novel molecular pathway involved in zoledronic acid-induced apoptosis of MDA-MB-231 cells in vitro.
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spelling pubmed-33600572012-05-31 Activation of BK(Ca) Channels in Zoledronic Acid-Induced Apoptosis of MDA-MB-231 Breast Cancer Cells Ma, Yu-Guang Liu, Wen-Chao Dong, Shuo Du, Cheng Wang, Xiao-Jun Li, Jin-Sheng Xie, Xiao-Ping Wu, Li Ma, Da-Chang Yu, Zhi-Bin Xie, Man-Jiang PLoS One Research Article BACKGROUND: Zoledronic acid, one of the most potent nitrogen-containing biphosphonates, has been demonstrated to have direct anti-tumor and anti-metastatic properties in breast cancer in vitro and in vivo. In particular, tumor-cell apoptosis has been recognized to play an important role in the treatment of metastatic breast cancer with zoledronic acid. However, the precise mechanisms remain less clear. In the present study, we investigated the specific role of large conductance Ca(2+)-activated potassium (BK(Ca)) channel in zoledronic acid-induced apoptosis of estrogen receptor (ER)-negative MDA-MB-231 breast cancer cells. METHODOLOGY/PRINCIPAL FINDINGS: The action of zoledronic acid on BK(Ca) channel was investigated by whole-cell and cell-attached patch clamp techniques. Cell apoptosis was assessed with immunocytochemistry, analysis of fragmented DNA by agarose gel electrophoresis, and flow cytometry assays. Cell proliferation was investigated by MTT test and immunocytochemistry. In addition, such findings were further confirmed with human embryonic kidney 293 (HEK293) cells which were transfected with functional BK(Ca) α-subunit (hSloα). Our results clearly indicated that zoledronic acid directly increased the activities of BK(Ca) channels, and then activation of BK(Ca) channel by zoledronic acid contributed to induce apoptosis in MDA-MB-231 cells. The possible mechanisms were associated with the elevated level of intracellular Ca(2+) and a concomitant depolarization of mitochondrial membrane potential (Δψm) in MDA-MB-231 cells. CONCLUSIONS: Activation of BK(Ca) channel was here shown to be a novel molecular pathway involved in zoledronic acid-induced apoptosis of MDA-MB-231 cells in vitro. Public Library of Science 2012-05-24 /pmc/articles/PMC3360057/ /pubmed/22655048 http://dx.doi.org/10.1371/journal.pone.0037451 Text en Ma et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ma, Yu-Guang
Liu, Wen-Chao
Dong, Shuo
Du, Cheng
Wang, Xiao-Jun
Li, Jin-Sheng
Xie, Xiao-Ping
Wu, Li
Ma, Da-Chang
Yu, Zhi-Bin
Xie, Man-Jiang
Activation of BK(Ca) Channels in Zoledronic Acid-Induced Apoptosis of MDA-MB-231 Breast Cancer Cells
title Activation of BK(Ca) Channels in Zoledronic Acid-Induced Apoptosis of MDA-MB-231 Breast Cancer Cells
title_full Activation of BK(Ca) Channels in Zoledronic Acid-Induced Apoptosis of MDA-MB-231 Breast Cancer Cells
title_fullStr Activation of BK(Ca) Channels in Zoledronic Acid-Induced Apoptosis of MDA-MB-231 Breast Cancer Cells
title_full_unstemmed Activation of BK(Ca) Channels in Zoledronic Acid-Induced Apoptosis of MDA-MB-231 Breast Cancer Cells
title_short Activation of BK(Ca) Channels in Zoledronic Acid-Induced Apoptosis of MDA-MB-231 Breast Cancer Cells
title_sort activation of bk(ca) channels in zoledronic acid-induced apoptosis of mda-mb-231 breast cancer cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3360057/
https://www.ncbi.nlm.nih.gov/pubmed/22655048
http://dx.doi.org/10.1371/journal.pone.0037451
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