Assim Khattab Hasan, Esmaeil Babaei, Ahmed Salim Kadhim Al-Khafaji
{"title":"Hesperetin effect on MLH1 and MSH2 expression on breast cancer cells BT-549.","authors":"Assim Khattab Hasan, Esmaeil Babaei, Ahmed Salim Kadhim Al-Khafaji","doi":"10.4103/japtr.japtr_277_23","DOIUrl":null,"url":null,"abstract":"<p><p>Due to its genetic and phenotypic heterogeneity, breast cancer is very difficult to eliminate. The harmful consequences of conventional therapies like radiation and chemotherapy have prompted the search for organic-based alternatives. Hesperetin (HSP), a flavonoid, has been discovered to possess the ability to hinder the proliferation of cell associated with breast cancer by acting as an epigenetic agent and modifying gene expression. In this investigation, breast cancer cells (BT-549) and normal cells (MCF-10a) were subjected to the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test and three different doses (200, 400, and 600 μM/mL) of HSP for real-time polymerase chain reaction and flow cytometry to examine its cytotoxic and anti-malignant potential. HSP was shown to be cytotoxic to both normal and breast cancer cells, but had a more pronounced effect on the cancer cell lines. After 48 h of treatment, the half-maximal inhibitory concentration (IC<sub>50</sub>) for BT-549 was 279.2 μM/mL, whereas the IC<sub>50</sub> for MCF-10a was 855.4 μM/mL. At high HSP concentrations, upregulation of the MLH1 and MSH2 genes was observed in both cell lines. The influence of HSP on MLH1 gene expression was concentration dependent. Moreover, HSP had a concentration-dependent effect on MSH2 gene expression in the BT-549 cell line but not in the MCF-10a cell line. Cell death and early apoptosis were shown to be concentration dependent upon the application of HSP, as determined by flow cytometric analysis. HSP's capacity to cause apoptosis and its stronger impact on the malignant cell line when analyzed with the normal cell line imply that it might be useful as an effective therapeutic approach for combating breast cancer.</p>","PeriodicalId":14877,"journal":{"name":"Journal of Advanced Pharmaceutical Technology & Research","volume":null,"pages":null},"PeriodicalIF":1.4000,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9f/b1/JAPTR-14-241.PMC10483912.pdf","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Advanced Pharmaceutical Technology & Research","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.4103/japtr.japtr_277_23","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/7/28 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"Pharmacology, Toxicology and Pharmaceutics","Score":null,"Total":0}
引用次数: 1
Abstract
Due to its genetic and phenotypic heterogeneity, breast cancer is very difficult to eliminate. The harmful consequences of conventional therapies like radiation and chemotherapy have prompted the search for organic-based alternatives. Hesperetin (HSP), a flavonoid, has been discovered to possess the ability to hinder the proliferation of cell associated with breast cancer by acting as an epigenetic agent and modifying gene expression. In this investigation, breast cancer cells (BT-549) and normal cells (MCF-10a) were subjected to the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test and three different doses (200, 400, and 600 μM/mL) of HSP for real-time polymerase chain reaction and flow cytometry to examine its cytotoxic and anti-malignant potential. HSP was shown to be cytotoxic to both normal and breast cancer cells, but had a more pronounced effect on the cancer cell lines. After 48 h of treatment, the half-maximal inhibitory concentration (IC50) for BT-549 was 279.2 μM/mL, whereas the IC50 for MCF-10a was 855.4 μM/mL. At high HSP concentrations, upregulation of the MLH1 and MSH2 genes was observed in both cell lines. The influence of HSP on MLH1 gene expression was concentration dependent. Moreover, HSP had a concentration-dependent effect on MSH2 gene expression in the BT-549 cell line but not in the MCF-10a cell line. Cell death and early apoptosis were shown to be concentration dependent upon the application of HSP, as determined by flow cytometric analysis. HSP's capacity to cause apoptosis and its stronger impact on the malignant cell line when analyzed with the normal cell line imply that it might be useful as an effective therapeutic approach for combating breast cancer.
期刊介绍:
Journal of Advanced Pharmaceutical Technology & Research (JAPTR) is an Official Publication of Society of Pharmaceutical Education & Research™. It is an international journal published Quarterly. Journal of Advanced Pharmaceutical Technology & Research (JAPTR) is available in online and print version. It is a peer reviewed journal aiming to communicate high quality original research work, reviews, short communications, case report, Ethics Forum, Education Forum and Letter to editor that contribute significantly to further the scientific knowledge related to the field of Pharmacy i.e. Pharmaceutics, Pharmacology, Pharmacognosy, Pharmaceutical Chemistry. Articles with timely interest and newer research concepts will be given more preference.