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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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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. |
format | Online Article Text |
id | pubmed-3360057 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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