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Lipidomic Analyses Uncover Apoptotic and Inhibitory Effects of Pyrvinium Pamoate on Cholangiocarcinoma Cells via Mitochondrial Membrane Potential Dysfunction

Pyrvinium pamoate (PP), an FDA-approved anthelmintic drug, has been validated as a highly potent anti-cancer agent and patented recently as a potential chemotherapeutic drug for various cancers. The aims of this study were, therefore, to investigate the ability of PP in anti-proliferative activity a...

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Autores principales: Kittirat, Yingpinyapat, Phetcharaburanin, Jutarop, Promraksa, Bundit, Kulthawatsiri, Thanaporn, Wangwiwatsin, Arporn, Klanrit, Poramate, Sangkhamanon, Sakkarn, Jarearnrat, Apiwat, Thongchot, Suyanee, Mahalapbutr, Panupong, Loilome, Watcharin, Saya, Hideyuki, Namwat, Nisana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8688698/
https://www.ncbi.nlm.nih.gov/pubmed/34950627
http://dx.doi.org/10.3389/fpubh.2021.766455
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author Kittirat, Yingpinyapat
Phetcharaburanin, Jutarop
Promraksa, Bundit
Kulthawatsiri, Thanaporn
Wangwiwatsin, Arporn
Klanrit, Poramate
Sangkhamanon, Sakkarn
Jarearnrat, Apiwat
Thongchot, Suyanee
Mahalapbutr, Panupong
Loilome, Watcharin
Saya, Hideyuki
Namwat, Nisana
author_facet Kittirat, Yingpinyapat
Phetcharaburanin, Jutarop
Promraksa, Bundit
Kulthawatsiri, Thanaporn
Wangwiwatsin, Arporn
Klanrit, Poramate
Sangkhamanon, Sakkarn
Jarearnrat, Apiwat
Thongchot, Suyanee
Mahalapbutr, Panupong
Loilome, Watcharin
Saya, Hideyuki
Namwat, Nisana
author_sort Kittirat, Yingpinyapat
collection PubMed
description Pyrvinium pamoate (PP), an FDA-approved anthelmintic drug, has been validated as a highly potent anti-cancer agent and patented recently as a potential chemotherapeutic drug for various cancers. The aims of this study were, therefore, to investigate the ability of PP in anti-proliferative activity and focused on the lipid profiles revealing the alteration of specific lipid species in the liver fluke Opisthorchis viverrini (Ov)-associated cholangiocarcinoma (CCA) cells. PP inhibited CCA cell viability through suppressing mitochondrial membrane potential (MMP) and ATP productions, leading to apoptotic cell death. Liquid chromatography-mass spectrometry combined with chemometrics was performed to investigate lipid alteration during PP-induced apoptosis. The lipidomic analyses showed the altered lipid signatures of CCA cell types including S-acetyldihydrolipoamide, methylselenopyruvate, and triglycerides that were increased in PP-treated CCA cells. In contrast, the levels of sphinganine and phosphatidylinositol were lower in the PP-treated group compared with its counterpart. The orthogonal partial-least squares regression analysis revealed that PP-induced MMP dysfunction, leading to remarkably reduced ATP level, was significantly associated with triglyceride (TG) accumulation observed in PP-treated CCA cells. Our findings indicate that PP could suppress the MMP function, which causes inhibition of CCA cell viability through lipid production, resulting in apoptotic induction in CCA cells. These findings provide an anti-cancer mechanism of PP under apoptotic induction ability that may serve as the alternative approach for CCA treatment.
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spelling pubmed-86886982021-12-22 Lipidomic Analyses Uncover Apoptotic and Inhibitory Effects of Pyrvinium Pamoate on Cholangiocarcinoma Cells via Mitochondrial Membrane Potential Dysfunction Kittirat, Yingpinyapat Phetcharaburanin, Jutarop Promraksa, Bundit Kulthawatsiri, Thanaporn Wangwiwatsin, Arporn Klanrit, Poramate Sangkhamanon, Sakkarn Jarearnrat, Apiwat Thongchot, Suyanee Mahalapbutr, Panupong Loilome, Watcharin Saya, Hideyuki Namwat, Nisana Front Public Health Public Health Pyrvinium pamoate (PP), an FDA-approved anthelmintic drug, has been validated as a highly potent anti-cancer agent and patented recently as a potential chemotherapeutic drug for various cancers. The aims of this study were, therefore, to investigate the ability of PP in anti-proliferative activity and focused on the lipid profiles revealing the alteration of specific lipid species in the liver fluke Opisthorchis viverrini (Ov)-associated cholangiocarcinoma (CCA) cells. PP inhibited CCA cell viability through suppressing mitochondrial membrane potential (MMP) and ATP productions, leading to apoptotic cell death. Liquid chromatography-mass spectrometry combined with chemometrics was performed to investigate lipid alteration during PP-induced apoptosis. The lipidomic analyses showed the altered lipid signatures of CCA cell types including S-acetyldihydrolipoamide, methylselenopyruvate, and triglycerides that were increased in PP-treated CCA cells. In contrast, the levels of sphinganine and phosphatidylinositol were lower in the PP-treated group compared with its counterpart. The orthogonal partial-least squares regression analysis revealed that PP-induced MMP dysfunction, leading to remarkably reduced ATP level, was significantly associated with triglyceride (TG) accumulation observed in PP-treated CCA cells. Our findings indicate that PP could suppress the MMP function, which causes inhibition of CCA cell viability through lipid production, resulting in apoptotic induction in CCA cells. These findings provide an anti-cancer mechanism of PP under apoptotic induction ability that may serve as the alternative approach for CCA treatment. Frontiers Media S.A. 2021-12-07 /pmc/articles/PMC8688698/ /pubmed/34950627 http://dx.doi.org/10.3389/fpubh.2021.766455 Text en Copyright © 2021 Kittirat, Phetcharaburanin, Promraksa, Kulthawatsiri, Wangwiwatsin, Klanrit, Sangkhamanon, Jarearnrat, Thongchot, Mahalapbutr, Loilome, Saya and Namwat. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Public Health
Kittirat, Yingpinyapat
Phetcharaburanin, Jutarop
Promraksa, Bundit
Kulthawatsiri, Thanaporn
Wangwiwatsin, Arporn
Klanrit, Poramate
Sangkhamanon, Sakkarn
Jarearnrat, Apiwat
Thongchot, Suyanee
Mahalapbutr, Panupong
Loilome, Watcharin
Saya, Hideyuki
Namwat, Nisana
Lipidomic Analyses Uncover Apoptotic and Inhibitory Effects of Pyrvinium Pamoate on Cholangiocarcinoma Cells via Mitochondrial Membrane Potential Dysfunction
title Lipidomic Analyses Uncover Apoptotic and Inhibitory Effects of Pyrvinium Pamoate on Cholangiocarcinoma Cells via Mitochondrial Membrane Potential Dysfunction
title_full Lipidomic Analyses Uncover Apoptotic and Inhibitory Effects of Pyrvinium Pamoate on Cholangiocarcinoma Cells via Mitochondrial Membrane Potential Dysfunction
title_fullStr Lipidomic Analyses Uncover Apoptotic and Inhibitory Effects of Pyrvinium Pamoate on Cholangiocarcinoma Cells via Mitochondrial Membrane Potential Dysfunction
title_full_unstemmed Lipidomic Analyses Uncover Apoptotic and Inhibitory Effects of Pyrvinium Pamoate on Cholangiocarcinoma Cells via Mitochondrial Membrane Potential Dysfunction
title_short Lipidomic Analyses Uncover Apoptotic and Inhibitory Effects of Pyrvinium Pamoate on Cholangiocarcinoma Cells via Mitochondrial Membrane Potential Dysfunction
title_sort lipidomic analyses uncover apoptotic and inhibitory effects of pyrvinium pamoate on cholangiocarcinoma cells via mitochondrial membrane potential dysfunction
topic Public Health
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8688698/
https://www.ncbi.nlm.nih.gov/pubmed/34950627
http://dx.doi.org/10.3389/fpubh.2021.766455
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