Effect of Clarithromycin on Enhancement of Doxorubicin-induced Cytotoxicity and Apoptosis in A549 Tumor-Cell Line

Background and purpose: Nowadays, multi-drug regimens or combination therapy are new approaches in cancer treatment that combine two or several therapeutic agents. Combination therapy aims at improving the therapeutic efficacy of anticancer drugs while reducing toxicity and preventing drug resistanc...

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Main Authors: Mohammad Shokrzadeh, Fatemeh Shaki, Nahid Amani
Format: Article
Language:English
Published: Mazandaran University of Medical Sciences 2022-10-01
Series:Journal of Mazandaran University of Medical Sciences
Subjects:
Online Access:http://jmums.mazums.ac.ir/article-1-18070-en.html
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author Mohammad Shokrzadeh
Fatemeh Shaki
Nahid Amani
author_facet Mohammad Shokrzadeh
Fatemeh Shaki
Nahid Amani
author_sort Mohammad Shokrzadeh
collection DOAJ
description Background and purpose: Nowadays, multi-drug regimens or combination therapy are new approaches in cancer treatment that combine two or several therapeutic agents. Combination therapy aims at improving the therapeutic efficacy of anticancer drugs while reducing toxicity and preventing drug resistance. The aim of this study was to determine the synergistic effect of combined clarithromycin and doxorubicin in lung cancer A549 cell line. Materials and methods: Combined cytotoxicity of doxorubicin and clarithromycin was evaluated by MTT assay in A549 cell line. The nature of the interaction observed between doxorubicin and clarithromycin was analyzed in Compusyn software based on Chou and Talalay method. In order to clarify the molecular mechanism of the drug synergism, apoptosis was measured by Annexin V/PI double staining. Results: Clarithromycin at 500 µM synergistically reduced the IC50 value of doxorubicin. The enhanced cytotoxicity of doxorubicin by clarithromycin was associated with increased apoptotic cell death in A549 cell line. Conclusion: Clarithromycin is a suitable candidate when combined with other anticancer drugs in vitro. However, more investigations are needed to evaluate the application of clarithromycin in adjuvant cancer therapy.
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spelling doaj.art-76834eea2f524a7fa1fc9217df108d962023-02-28T09:08:45ZengMazandaran University of Medical SciencesJournal of Mazandaran University of Medical Sciences1735-92601735-92792022-10-01322134254Effect of Clarithromycin on Enhancement of Doxorubicin-induced Cytotoxicity and Apoptosis in A549 Tumor-Cell LineMohammad Shokrzadeh0Fatemeh Shaki1Nahid Amani2 Professor, Department of Toxicology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran Associate Professor, Pharmaceutical Sciences Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran . Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran PhD in Toxicology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran Background and purpose: Nowadays, multi-drug regimens or combination therapy are new approaches in cancer treatment that combine two or several therapeutic agents. Combination therapy aims at improving the therapeutic efficacy of anticancer drugs while reducing toxicity and preventing drug resistance. The aim of this study was to determine the synergistic effect of combined clarithromycin and doxorubicin in lung cancer A549 cell line. Materials and methods: Combined cytotoxicity of doxorubicin and clarithromycin was evaluated by MTT assay in A549 cell line. The nature of the interaction observed between doxorubicin and clarithromycin was analyzed in Compusyn software based on Chou and Talalay method. In order to clarify the molecular mechanism of the drug synergism, apoptosis was measured by Annexin V/PI double staining. Results: Clarithromycin at 500 µM synergistically reduced the IC50 value of doxorubicin. The enhanced cytotoxicity of doxorubicin by clarithromycin was associated with increased apoptotic cell death in A549 cell line. Conclusion: Clarithromycin is a suitable candidate when combined with other anticancer drugs in vitro. However, more investigations are needed to evaluate the application of clarithromycin in adjuvant cancer therapy.http://jmums.mazums.ac.ir/article-1-18070-en.htmldoxorubicinclarithromycincombination therapysynergismapoptosis
spellingShingle Mohammad Shokrzadeh
Fatemeh Shaki
Nahid Amani
Effect of Clarithromycin on Enhancement of Doxorubicin-induced Cytotoxicity and Apoptosis in A549 Tumor-Cell Line
Journal of Mazandaran University of Medical Sciences
doxorubicin
clarithromycin
combination therapy
synergism
apoptosis
title Effect of Clarithromycin on Enhancement of Doxorubicin-induced Cytotoxicity and Apoptosis in A549 Tumor-Cell Line
title_full Effect of Clarithromycin on Enhancement of Doxorubicin-induced Cytotoxicity and Apoptosis in A549 Tumor-Cell Line
title_fullStr Effect of Clarithromycin on Enhancement of Doxorubicin-induced Cytotoxicity and Apoptosis in A549 Tumor-Cell Line
title_full_unstemmed Effect of Clarithromycin on Enhancement of Doxorubicin-induced Cytotoxicity and Apoptosis in A549 Tumor-Cell Line
title_short Effect of Clarithromycin on Enhancement of Doxorubicin-induced Cytotoxicity and Apoptosis in A549 Tumor-Cell Line
title_sort effect of clarithromycin on enhancement of doxorubicin induced cytotoxicity and apoptosis in a549 tumor cell line
topic doxorubicin
clarithromycin
combination therapy
synergism
apoptosis
url http://jmums.mazums.ac.ir/article-1-18070-en.html
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AT fatemehshaki effectofclarithromycinonenhancementofdoxorubicininducedcytotoxicityandapoptosisina549tumorcellline
AT nahidamani effectofclarithromycinonenhancementofdoxorubicininducedcytotoxicityandapoptosisina549tumorcellline