Autophagy and apoptosis in hepatocellular carcinoma induced by EF25-(GSH)2: a novel curcumin analog.

Curcumin, a spice component as well as a traditional Asian medicine, has been reported to inhibit proliferation of a variety of cancer cells but is limited in application due to its low potency and bioavailability. Here, we have assessed the therapeutic effects of a novel and water soluble curcumin...

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Autores principales:	Tao Zhou, Lili Ye, Yu Bai, Aiming Sun, Bryan Cox, Dahai Liu, Yong Li, Dennis Liotta, James P Snyder, Haian Fu, Bei Huang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8a867c3bb3414918b4ed53e2a6017339
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spelling	oai:doaj.org-article:8a867c3bb3414918b4ed53e2a60173392021-11-25T05:58:43ZAutophagy and apoptosis in hepatocellular carcinoma induced by EF25-(GSH)2: a novel curcumin analog.1932-620310.1371/journal.pone.0107876https://doaj.org/article/8a867c3bb3414918b4ed53e2a60173392014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0107876https://doaj.org/toc/1932-6203Curcumin, a spice component as well as a traditional Asian medicine, has been reported to inhibit proliferation of a variety of cancer cells but is limited in application due to its low potency and bioavailability. Here, we have assessed the therapeutic effects of a novel and water soluble curcumin analog, 3,5-bis(2-hydroxybenzylidene)tetrahydro-4H-pyran-4-one glutathione conjugate [EF25-(GSH)2], on hepatoma cells. Using the MTT and colony formation assays, we determined that EF25-(GSH)2 drastically inhibits the proliferation of hepatoma cell line HepG2 with minimal cytotoxicity for the immortalized human hepatic cell line HL-7702. Significantly, EF25-(GSH)2 suppressed growth of HepG2 xenografts in mice with no observed toxicity to the animals. Mechanistic investigation revealed that EF25-(GSH)2 induces autophagy by means of a biphasic mechanism. Low concentrations (<5 µmol/L) induced autophagy with reversible and moderate cytoplasmic vacuolization, while high concentrations (>10 µmol/L) triggered an arrested autophagy process with irreversible and extensive cytoplasmic vacuolization. Prolonged treatment with EF25-(GSH)2 induced cell death through both an apoptosis-dependent and a non-apoptotic mechanism. Chloroquine, a late stage inhibitor of autophagy which promoted cytoplasmic vacuolization, led to significantly enhanced apoptosis and cytotoxicity when combined with EF25-(GSH)2. Taken together, these data imply a fail-safe mechanism regulated by autophagy in the action of EF25-(GSH)2, suggesting the therapeutic potential of the novel curcumin analog against hepatocellular carcinoma (HCC), while offering a novel and effective combination strategy with chloroquine for the treatment of patients with HCC.Tao ZhouLili YeYu BaiAiming SunBryan CoxDahai LiuYong LiDennis LiottaJames P SnyderHaian FuBei HuangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 9, p e107876 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tao Zhou Lili Ye Yu Bai Aiming Sun Bryan Cox Dahai Liu Yong Li Dennis Liotta James P Snyder Haian Fu Bei Huang Autophagy and apoptosis in hepatocellular carcinoma induced by EF25-(GSH)2: a novel curcumin analog.
description	Curcumin, a spice component as well as a traditional Asian medicine, has been reported to inhibit proliferation of a variety of cancer cells but is limited in application due to its low potency and bioavailability. Here, we have assessed the therapeutic effects of a novel and water soluble curcumin analog, 3,5-bis(2-hydroxybenzylidene)tetrahydro-4H-pyran-4-one glutathione conjugate [EF25-(GSH)2], on hepatoma cells. Using the MTT and colony formation assays, we determined that EF25-(GSH)2 drastically inhibits the proliferation of hepatoma cell line HepG2 with minimal cytotoxicity for the immortalized human hepatic cell line HL-7702. Significantly, EF25-(GSH)2 suppressed growth of HepG2 xenografts in mice with no observed toxicity to the animals. Mechanistic investigation revealed that EF25-(GSH)2 induces autophagy by means of a biphasic mechanism. Low concentrations (<5 µmol/L) induced autophagy with reversible and moderate cytoplasmic vacuolization, while high concentrations (>10 µmol/L) triggered an arrested autophagy process with irreversible and extensive cytoplasmic vacuolization. Prolonged treatment with EF25-(GSH)2 induced cell death through both an apoptosis-dependent and a non-apoptotic mechanism. Chloroquine, a late stage inhibitor of autophagy which promoted cytoplasmic vacuolization, led to significantly enhanced apoptosis and cytotoxicity when combined with EF25-(GSH)2. Taken together, these data imply a fail-safe mechanism regulated by autophagy in the action of EF25-(GSH)2, suggesting the therapeutic potential of the novel curcumin analog against hepatocellular carcinoma (HCC), while offering a novel and effective combination strategy with chloroquine for the treatment of patients with HCC.
format	article
author	Tao Zhou Lili Ye Yu Bai Aiming Sun Bryan Cox Dahai Liu Yong Li Dennis Liotta James P Snyder Haian Fu Bei Huang
author_facet	Tao Zhou Lili Ye Yu Bai Aiming Sun Bryan Cox Dahai Liu Yong Li Dennis Liotta James P Snyder Haian Fu Bei Huang
author_sort	Tao Zhou
title	Autophagy and apoptosis in hepatocellular carcinoma induced by EF25-(GSH)2: a novel curcumin analog.
title_short	Autophagy and apoptosis in hepatocellular carcinoma induced by EF25-(GSH)2: a novel curcumin analog.
title_full	Autophagy and apoptosis in hepatocellular carcinoma induced by EF25-(GSH)2: a novel curcumin analog.
title_fullStr	Autophagy and apoptosis in hepatocellular carcinoma induced by EF25-(GSH)2: a novel curcumin analog.
title_full_unstemmed	Autophagy and apoptosis in hepatocellular carcinoma induced by EF25-(GSH)2: a novel curcumin analog.
title_sort	autophagy and apoptosis in hepatocellular carcinoma induced by ef25-(gsh)2: a novel curcumin analog.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/8a867c3bb3414918b4ed53e2a6017339
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Autophagy and apoptosis in hepatocellular carcinoma induced by EF25-(GSH)2: a novel curcumin analog.

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