Open AccessEffect of Melatonin on Reversing Multidrug Resistance by Targeting Phosphatase and Tensin Homolog in Leukemia Cancer Cells
Publication year - 2021
Publication title -
iranian red crescent medical journal
Language(s) - English
Resource type - Journals
ISSN - 2074-1804
DOI - 10.32592/ircmj.2021.23.7.212
Subject(s) - melatonin , tensin , k562 cells , pten , leukemia , multiple drug resistance , cancer research , apoptosis , p glycoprotein , annexin , cytotoxicity , biology , pharmacology , immunology , drug resistance , endocrinology , biochemistry , pi3k/akt/mtor pathway , in vitro , microbiology and biotechnology
Background: Recently, melatonin has attracted massive attention due to its anticancer effect on various human malignancies. It has also been demonstrated that melatonin is useful in combating resistance against conventional chemotherapeutics. Objective: This study aimed to evaluate melatonin’s effects on multidrug resistance (MDR) in human myelogenous leukemia cells. Methods: Melatonin’s cytotoxicity on the K562 and K562/doxorubicin (DOX) cell lines was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression and activity of P-glycoprotein (P-gp) were measured as well. The mRNA and protein expression levels of tensin homolog deleted on chromosome ten (PTEN) was assessed in cells. Eventually, apoptosis in cancer cells was measured through Annexin V/PI staining. Results: Treatment with melatonin significantly increased the cytotoxicity of DOX in resistant K562 cells. The expression and activity of P-gp were attenuated following melatonin treatment. In addition, melatonin upregulated PTEN in K562/DOX cells. Melatonin also augmented apoptosis in combination with DOX. Conclusion: Melatonin effectively increased the cytotoxic effects of DOX in K562/DOX cells through down-regulation of P-gp and up-regulation of PTEN in resistant K562 cells.