Zoledronic acid induces autophagic cell death in human prostate cancer cells

Ji Fan Lin, Yi Chia Lin, Yi Hsuan Lin, Te Fu Tsai, Kuang Yu Chou, Hung En Chen, Yi-Sheng Huang

研究成果: 雜誌貢獻文章

36 引文 (Scopus)

摘要

Purpose: Bisphosphonates are potent inhibitors of bone resorption. In vitro studies show that zolendronic acid inhibits prostate cancer cell growth by activating apoptosis. We investigated whether zolendronic acid also inhibits prostate cancer cell growth by autophagy (type II programmed cell death). Materials and Methods: We investigated the induction of autophagy in the PC-3, DU-145, LNCaP and CRW22Rv1 cell lines upon zolendronic acid treatment. LC3-II protein formation was detected by Western blot. LC3-II incorporation into autophagosomes was detected by immunofluorescence staining. Acidic organelle formation was detected by acridine orange staining. Rescue experiments using an apoptosis inhibitor and/or an autophagy inhibitor were performed by MTT assay. Results: Autophagy induction was detected by formation of the LC3-II protein after exposure to 100 μM zolendronic acid. LC3-II and caspase-3 processing was detected 6 days after treatment. Acidic organelles were detectable by acridine orange staining and immunofluorescence showed round-up and condensed staining of LC3-II, suggesting autophagosome formation in the cytoplasm during autophagic cell death. Cell growth was rescued only by administering an apoptosis and autophagy inhibitor during zolendronic acid treatment, indicating that zolendronic acid induces prostate cancer death by apoptotic and autophagic cell death. Conclusions: To our knowledge we report the first study showing that zolendronic acid markedly inhibits human prostate cancer cell growth through autophagic cell death. Zolendronic acid shows its anticancer activity via apoptosis and autophagy. These findings can potentially contribute to the beneficial use of zolendronic acid for prostate cancer treatment.
原文英語
頁(從 - 到)1490-1496
頁數7
期刊Journal of Urology
185
發行號4
DOIs
出版狀態已發佈 - 四月 2011

指紋

zoledronic acid
Autophagy
Prostatic Neoplasms
Acids
Apoptosis
Staining and Labeling
Acridine Orange
Growth
Organelles
Fluorescent Antibody Technique
Bone Density Conservation Agents

ASJC Scopus subject areas

  • Urology

引用此文

Lin, J. F., Lin, Y. C., Lin, Y. H., Tsai, T. F., Chou, K. Y., Chen, H. E., & Huang, Y-S. (2011). Zoledronic acid induces autophagic cell death in human prostate cancer cells. Journal of Urology, 185(4), 1490-1496. https://doi.org/10.1016/j.juro.2010.11.045

Zoledronic acid induces autophagic cell death in human prostate cancer cells. / Lin, Ji Fan; Lin, Yi Chia; Lin, Yi Hsuan; Tsai, Te Fu; Chou, Kuang Yu; Chen, Hung En; Huang, Yi-Sheng.

於: Journal of Urology, 卷 185, 編號 4, 04.2011, p. 1490-1496.

研究成果: 雜誌貢獻文章

Lin, JF, Lin, YC, Lin, YH, Tsai, TF, Chou, KY, Chen, HE & Huang, Y-S 2011, 'Zoledronic acid induces autophagic cell death in human prostate cancer cells', Journal of Urology, 卷 185, 編號 4, 頁 1490-1496. https://doi.org/10.1016/j.juro.2010.11.045
Lin, Ji Fan ; Lin, Yi Chia ; Lin, Yi Hsuan ; Tsai, Te Fu ; Chou, Kuang Yu ; Chen, Hung En ; Huang, Yi-Sheng. / Zoledronic acid induces autophagic cell death in human prostate cancer cells. 於: Journal of Urology. 2011 ; 卷 185, 編號 4. 頁 1490-1496.
@article{8be806c7ff6041aabb762d7eef00bb87,
title = "Zoledronic acid induces autophagic cell death in human prostate cancer cells",
abstract = "Purpose: Bisphosphonates are potent inhibitors of bone resorption. In vitro studies show that zolendronic acid inhibits prostate cancer cell growth by activating apoptosis. We investigated whether zolendronic acid also inhibits prostate cancer cell growth by autophagy (type II programmed cell death). Materials and Methods: We investigated the induction of autophagy in the PC-3, DU-145, LNCaP and CRW22Rv1 cell lines upon zolendronic acid treatment. LC3-II protein formation was detected by Western blot. LC3-II incorporation into autophagosomes was detected by immunofluorescence staining. Acidic organelle formation was detected by acridine orange staining. Rescue experiments using an apoptosis inhibitor and/or an autophagy inhibitor were performed by MTT assay. Results: Autophagy induction was detected by formation of the LC3-II protein after exposure to 100 μM zolendronic acid. LC3-II and caspase-3 processing was detected 6 days after treatment. Acidic organelles were detectable by acridine orange staining and immunofluorescence showed round-up and condensed staining of LC3-II, suggesting autophagosome formation in the cytoplasm during autophagic cell death. Cell growth was rescued only by administering an apoptosis and autophagy inhibitor during zolendronic acid treatment, indicating that zolendronic acid induces prostate cancer death by apoptotic and autophagic cell death. Conclusions: To our knowledge we report the first study showing that zolendronic acid markedly inhibits human prostate cancer cell growth through autophagic cell death. Zolendronic acid shows its anticancer activity via apoptosis and autophagy. These findings can potentially contribute to the beneficial use of zolendronic acid for prostate cancer treatment.",
keywords = "apoptosis, autophagy, prostate, prostatic neoplasms, zoledronic acid",
author = "Lin, {Ji Fan} and Lin, {Yi Chia} and Lin, {Yi Hsuan} and Tsai, {Te Fu} and Chou, {Kuang Yu} and Chen, {Hung En} and Yi-Sheng Huang",
year = "2011",
month = "4",
doi = "10.1016/j.juro.2010.11.045",
language = "English",
volume = "185",
pages = "1490--1496",
journal = "Journal of Urology",
issn = "0022-5347",
publisher = "Elsevier Inc.",
number = "4",

}

TY - JOUR

T1 - Zoledronic acid induces autophagic cell death in human prostate cancer cells

AU - Lin, Ji Fan

AU - Lin, Yi Chia

AU - Lin, Yi Hsuan

AU - Tsai, Te Fu

AU - Chou, Kuang Yu

AU - Chen, Hung En

AU - Huang, Yi-Sheng

PY - 2011/4

Y1 - 2011/4

N2 - Purpose: Bisphosphonates are potent inhibitors of bone resorption. In vitro studies show that zolendronic acid inhibits prostate cancer cell growth by activating apoptosis. We investigated whether zolendronic acid also inhibits prostate cancer cell growth by autophagy (type II programmed cell death). Materials and Methods: We investigated the induction of autophagy in the PC-3, DU-145, LNCaP and CRW22Rv1 cell lines upon zolendronic acid treatment. LC3-II protein formation was detected by Western blot. LC3-II incorporation into autophagosomes was detected by immunofluorescence staining. Acidic organelle formation was detected by acridine orange staining. Rescue experiments using an apoptosis inhibitor and/or an autophagy inhibitor were performed by MTT assay. Results: Autophagy induction was detected by formation of the LC3-II protein after exposure to 100 μM zolendronic acid. LC3-II and caspase-3 processing was detected 6 days after treatment. Acidic organelles were detectable by acridine orange staining and immunofluorescence showed round-up and condensed staining of LC3-II, suggesting autophagosome formation in the cytoplasm during autophagic cell death. Cell growth was rescued only by administering an apoptosis and autophagy inhibitor during zolendronic acid treatment, indicating that zolendronic acid induces prostate cancer death by apoptotic and autophagic cell death. Conclusions: To our knowledge we report the first study showing that zolendronic acid markedly inhibits human prostate cancer cell growth through autophagic cell death. Zolendronic acid shows its anticancer activity via apoptosis and autophagy. These findings can potentially contribute to the beneficial use of zolendronic acid for prostate cancer treatment.

AB - Purpose: Bisphosphonates are potent inhibitors of bone resorption. In vitro studies show that zolendronic acid inhibits prostate cancer cell growth by activating apoptosis. We investigated whether zolendronic acid also inhibits prostate cancer cell growth by autophagy (type II programmed cell death). Materials and Methods: We investigated the induction of autophagy in the PC-3, DU-145, LNCaP and CRW22Rv1 cell lines upon zolendronic acid treatment. LC3-II protein formation was detected by Western blot. LC3-II incorporation into autophagosomes was detected by immunofluorescence staining. Acidic organelle formation was detected by acridine orange staining. Rescue experiments using an apoptosis inhibitor and/or an autophagy inhibitor were performed by MTT assay. Results: Autophagy induction was detected by formation of the LC3-II protein after exposure to 100 μM zolendronic acid. LC3-II and caspase-3 processing was detected 6 days after treatment. Acidic organelles were detectable by acridine orange staining and immunofluorescence showed round-up and condensed staining of LC3-II, suggesting autophagosome formation in the cytoplasm during autophagic cell death. Cell growth was rescued only by administering an apoptosis and autophagy inhibitor during zolendronic acid treatment, indicating that zolendronic acid induces prostate cancer death by apoptotic and autophagic cell death. Conclusions: To our knowledge we report the first study showing that zolendronic acid markedly inhibits human prostate cancer cell growth through autophagic cell death. Zolendronic acid shows its anticancer activity via apoptosis and autophagy. These findings can potentially contribute to the beneficial use of zolendronic acid for prostate cancer treatment.

KW - apoptosis

KW - autophagy

KW - prostate

KW - prostatic neoplasms

KW - zoledronic acid

UR - http://www.scopus.com/inward/record.url?scp=79952696802&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79952696802&partnerID=8YFLogxK

U2 - 10.1016/j.juro.2010.11.045

DO - 10.1016/j.juro.2010.11.045

M3 - Article

C2 - 21334668

AN - SCOPUS:79952696802

VL - 185

SP - 1490

EP - 1496

JO - Journal of Urology

JF - Journal of Urology

SN - 0022-5347

IS - 4

ER -