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Ivermectin and gemcitabine combination treatment induces apoptosis of pancreatic cancer cells via mitochondrial dysfunction

Pancreatic cancer is an aggressive cancer characterized by high mortality and poor prognosis, with a survival rate of less than 5 years in advanced stages. Ivermectin, an antiparasitic drug, exerts antitumor effects in various cancer types. This is the first study to evaluate the anticancer effects...

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Autores principales: Lee, Da Eun, Kang, Hyeon Woong, Kim, So Yi, Kim, Myeong Jin, Jeong, Jae Woong, Hong, Woosol Chris, Fang, Sungsoon, Kim, Hyung Sun, Lee, Yun Sun, Kim, Hyo Jung, Park, Joon Seong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9459089/
https://www.ncbi.nlm.nih.gov/pubmed/36091811
http://dx.doi.org/10.3389/fphar.2022.934746
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author Lee, Da Eun
Kang, Hyeon Woong
Kim, So Yi
Kim, Myeong Jin
Jeong, Jae Woong
Hong, Woosol Chris
Fang, Sungsoon
Kim, Hyung Sun
Lee, Yun Sun
Kim, Hyo Jung
Park, Joon Seong
author_facet Lee, Da Eun
Kang, Hyeon Woong
Kim, So Yi
Kim, Myeong Jin
Jeong, Jae Woong
Hong, Woosol Chris
Fang, Sungsoon
Kim, Hyung Sun
Lee, Yun Sun
Kim, Hyo Jung
Park, Joon Seong
author_sort Lee, Da Eun
collection PubMed
description Pancreatic cancer is an aggressive cancer characterized by high mortality and poor prognosis, with a survival rate of less than 5 years in advanced stages. Ivermectin, an antiparasitic drug, exerts antitumor effects in various cancer types. This is the first study to evaluate the anticancer effects of the combination of ivermectin and gemcitabine in pancreatic cancer. We found that the ivermectin–gemcitabine combination treatment suppressed pancreatic cancer more effectively than gemcitabine alone treatment. The ivermectin–gemcitabine combination inhibited cell proliferation via G1 arrest of the cell cycle, as evidenced by the downregulation of cyclin D1 expression and the mammalian target of rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT-3) signaling pathway. Ivermectin–gemcitabine increased cell apoptosis by inducing mitochondrial dysfunction via the overproduction of reactive oxygen species and decreased the mitochondrial membrane potential. This combination treatment also decreased the oxygen consumption rate and inhibited mitophagy, which is important for cancer cell death. Moreover, in vivo experiments confirmed that the ivermectin–gemcitabine group had significantly suppressed tumor growth compared to the gemcitabine alone group. These results indicate that ivermectin exerts synergistic effects with gemcitabine, preventing pancreatic cancer progression, and could be a potential antitumor drug for the treatment of pancreatic cancer.
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spelling pubmed-94590892022-09-10 Ivermectin and gemcitabine combination treatment induces apoptosis of pancreatic cancer cells via mitochondrial dysfunction Lee, Da Eun Kang, Hyeon Woong Kim, So Yi Kim, Myeong Jin Jeong, Jae Woong Hong, Woosol Chris Fang, Sungsoon Kim, Hyung Sun Lee, Yun Sun Kim, Hyo Jung Park, Joon Seong Front Pharmacol Pharmacology Pancreatic cancer is an aggressive cancer characterized by high mortality and poor prognosis, with a survival rate of less than 5 years in advanced stages. Ivermectin, an antiparasitic drug, exerts antitumor effects in various cancer types. This is the first study to evaluate the anticancer effects of the combination of ivermectin and gemcitabine in pancreatic cancer. We found that the ivermectin–gemcitabine combination treatment suppressed pancreatic cancer more effectively than gemcitabine alone treatment. The ivermectin–gemcitabine combination inhibited cell proliferation via G1 arrest of the cell cycle, as evidenced by the downregulation of cyclin D1 expression and the mammalian target of rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT-3) signaling pathway. Ivermectin–gemcitabine increased cell apoptosis by inducing mitochondrial dysfunction via the overproduction of reactive oxygen species and decreased the mitochondrial membrane potential. This combination treatment also decreased the oxygen consumption rate and inhibited mitophagy, which is important for cancer cell death. Moreover, in vivo experiments confirmed that the ivermectin–gemcitabine group had significantly suppressed tumor growth compared to the gemcitabine alone group. These results indicate that ivermectin exerts synergistic effects with gemcitabine, preventing pancreatic cancer progression, and could be a potential antitumor drug for the treatment of pancreatic cancer. Frontiers Media S.A. 2022-08-26 /pmc/articles/PMC9459089/ /pubmed/36091811 http://dx.doi.org/10.3389/fphar.2022.934746 Text en Copyright © 2022 Lee, Kang, Kim, Kim, Jeong, Hong, Fang, Kim, Lee, Kim and Park. 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 Pharmacology
Lee, Da Eun
Kang, Hyeon Woong
Kim, So Yi
Kim, Myeong Jin
Jeong, Jae Woong
Hong, Woosol Chris
Fang, Sungsoon
Kim, Hyung Sun
Lee, Yun Sun
Kim, Hyo Jung
Park, Joon Seong
Ivermectin and gemcitabine combination treatment induces apoptosis of pancreatic cancer cells via mitochondrial dysfunction
title Ivermectin and gemcitabine combination treatment induces apoptosis of pancreatic cancer cells via mitochondrial dysfunction
title_full Ivermectin and gemcitabine combination treatment induces apoptosis of pancreatic cancer cells via mitochondrial dysfunction
title_fullStr Ivermectin and gemcitabine combination treatment induces apoptosis of pancreatic cancer cells via mitochondrial dysfunction
title_full_unstemmed Ivermectin and gemcitabine combination treatment induces apoptosis of pancreatic cancer cells via mitochondrial dysfunction
title_short Ivermectin and gemcitabine combination treatment induces apoptosis of pancreatic cancer cells via mitochondrial dysfunction
title_sort ivermectin and gemcitabine combination treatment induces apoptosis of pancreatic cancer cells via mitochondrial dysfunction
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9459089/
https://www.ncbi.nlm.nih.gov/pubmed/36091811
http://dx.doi.org/10.3389/fphar.2022.934746
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