Nonautophagic cytoplasmic vacuolation death induction in human PC-3M prostate cancer by curcumin through reactive oxygen species -mediated endoplasmic reticulum stress

Wei Jiunn Lee, Ming Hsien Chien, Jyh Ming Chow, Junn Liang Chang, Yu-Ching Wen, Yung Wei Lin, Chao Wen Cheng, Gi Ming Lai, Michael Hsiao, Liang Ming Lee

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Abstract

The antiapoptotic and antiautophagic abilities of cancer cells constitute a major challenge for anticancer drug treatment. Strategies for triggering nonapoptotic or nonautophagic cell death may improve therapeutic efficacy against cancer. Curcumin has been reported to exhibit cancer chemopreventive properties. Herein, we report that curcumin induced apoptosis in LNCaP, DU145, and PC-3 cells but triggered extensive cytoplasmic vacuolation in PC-3M cells. Electron microscopic images showed that the vacuoles lacked intracellular organelles and were derived from the endoplasmic reticulum (ER). Moreover, curcumin-induced vacuolation was not reversed by an apoptosis- or autophagy-related inhibitor, suggesting that vacuolation-mediated cell death differs from classical apoptotic and autophagic cell death. Mechanistic investigations revealed that curcumin treatment upregulated the ER stress markers CHOP and Bip/GRP78 and the autophagic marker LC3-II. In addition, curcumin induced ER stress by triggering ROS generation, which was supported by the finding that treating cells with the antioxidant NAC alleviated curcumin-mediated ER stress and vacuolation-mediated death. An in vivo PC-3M orthotopic prostate cancer model revealed that curcumin reduced tumor growth by inducing ROS production followed by vacuolation-mediated cell death. Overall, our results indicated that curcumin acts as an inducer of ROS production, which leads to nonapoptotic and nonautophagic cell death via increased ER stress.

Original languageEnglish
Article number10420
JournalScientific Reports
Volume5
DOIs
Publication statusPublished - May 27 2015

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Endoplasmic Reticulum Stress
Curcumin
Reactive Oxygen Species
Prostatic Neoplasms
Cell Death
Autophagy
Neoplasms
Apoptosis
Vacuoles
Endoplasmic Reticulum
Organelles
Antioxidants
Electrons
Growth

ASJC Scopus subject areas

  • General

Cite this

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title = "Nonautophagic cytoplasmic vacuolation death induction in human PC-3M prostate cancer by curcumin through reactive oxygen species -mediated endoplasmic reticulum stress",
abstract = "The antiapoptotic and antiautophagic abilities of cancer cells constitute a major challenge for anticancer drug treatment. Strategies for triggering nonapoptotic or nonautophagic cell death may improve therapeutic efficacy against cancer. Curcumin has been reported to exhibit cancer chemopreventive properties. Herein, we report that curcumin induced apoptosis in LNCaP, DU145, and PC-3 cells but triggered extensive cytoplasmic vacuolation in PC-3M cells. Electron microscopic images showed that the vacuoles lacked intracellular organelles and were derived from the endoplasmic reticulum (ER). Moreover, curcumin-induced vacuolation was not reversed by an apoptosis- or autophagy-related inhibitor, suggesting that vacuolation-mediated cell death differs from classical apoptotic and autophagic cell death. Mechanistic investigations revealed that curcumin treatment upregulated the ER stress markers CHOP and Bip/GRP78 and the autophagic marker LC3-II. In addition, curcumin induced ER stress by triggering ROS generation, which was supported by the finding that treating cells with the antioxidant NAC alleviated curcumin-mediated ER stress and vacuolation-mediated death. An in vivo PC-3M orthotopic prostate cancer model revealed that curcumin reduced tumor growth by inducing ROS production followed by vacuolation-mediated cell death. Overall, our results indicated that curcumin acts as an inducer of ROS production, which leads to nonapoptotic and nonautophagic cell death via increased ER stress.",
author = "Lee, {Wei Jiunn} and Chien, {Ming Hsien} and Chow, {Jyh Ming} and Chang, {Junn Liang} and Yu-Ching Wen and Lin, {Yung Wei} and Cheng, {Chao Wen} and Lai, {Gi Ming} and Michael Hsiao and Lee, {Liang Ming}",
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AU - Chang, Junn Liang

AU - Wen, Yu-Ching

AU - Lin, Yung Wei

AU - Cheng, Chao Wen

AU - Lai, Gi Ming

AU - Hsiao, Michael

AU - Lee, Liang Ming

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