TY - JOUR
T1 - Lipidomic Analyses Uncover Apoptotic and Inhibitory Effects of Pyrvinium Pamoate on Cholangiocarcinoma Cells via Mitochondrial Membrane Potential Dysfunction
AU - Kittirat, Yingpinyapat
AU - Phetcharaburanin, Jutarop
AU - Promraksa, Bundit
AU - Kulthawatsiri, Thanaporn
AU - Wangwiwatsin, Arporn
AU - Klanrit, Poramate
AU - Sangkhamanon, Sakkarn
AU - Jarearnrat, Apiwat
AU - Thongchot, Suyanee
AU - Mahalapbutr, Panupong
AU - Loilome, Watcharin
AU - Saya, Hideyuki
AU - Namwat, Nisana
N1 - Funding Information:
This work was supported by the Thailand Research Fund through Khon Kaen University and The Royal Golden Jubilee Ph.D. Program (Grant no. PHD/0215/2560) to YK and NN, a grant from Faculty of Medicine, Khon Kaen University (Grant no. IN62305), and the NSRF under the Basic Research Fund of Khon Kaen University under through Cholangiocarcinoma Research Institute to NN.
Publisher Copyright:
Copyright © 2021 Kittirat, Phetcharaburanin, Promraksa, Kulthawatsiri, Wangwiwatsin, Klanrit, Sangkhamanon, Jarearnrat, Thongchot, Mahalapbutr, Loilome, Saya and Namwat.
PY - 2021/12/7
Y1 - 2021/12/7
N2 - 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.
AB - 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.
KW - apoptosis
KW - cholangiocarcinoma
KW - lipidomic
KW - mitochondrial membrane potential dysfunction
KW - pyrvinium pamoate
UR - http://www.scopus.com/inward/record.url?scp=85121620131&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85121620131&partnerID=8YFLogxK
U2 - 10.3389/fpubh.2021.766455
DO - 10.3389/fpubh.2021.766455
M3 - Article
C2 - 34950627
AN - SCOPUS:85121620131
SN - 2296-2565
VL - 9
JO - Frontiers in Public Health
JF - Frontiers in Public Health
M1 - 766455
ER -