Hesperetin effect on MLH1 and MSH2 expression on breast cancer cells BT-549.

IF 1.4 Q3 Pharmacology, Toxicology and Pharmaceutics Journal of Advanced Pharmaceutical Technology & Research Pub Date : 2023-07-01 Epub Date: 2023-07-28 DOI:10.4103/japtr.japtr_277_23
Assim Khattab Hasan, Esmaeil Babaei, Ahmed Salim Kadhim Al-Khafaji
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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.

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Hespeerin对乳腺癌症细胞BT-549 MLH1和MSH2表达的影响。
由于其遗传和表型的异质性,癌症很难消除。放疗和化疗等传统疗法的有害后果促使人们寻找基于有机物的替代品。Hespeerin(HSP)是一种黄酮类化合物,被发现具有作为表观遗传因子和修饰基因表达来抑制癌症相关细胞增殖的能力。在本研究中,对乳腺癌症细胞(BT-549)和正常细胞(MCF-10a)进行3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑鎓)试验和三种不同剂量(200、400和600μM/mL)的HSP实时聚合酶链反应和流式细胞术,以检测其细胞毒性和抗恶性潜力。HSP对正常和乳腺癌症细胞均具有细胞毒性,但对癌症细胞系具有更显著的作用。治疗48小时后,BT-549的半数最大抑制浓度(IC50)为279.2μM/mL,而MCF-10a的IC50为855.4μM/mL。在高HSP浓度下,在两种细胞系中都观察到MLH1和MSH2基因的上调。HSP对MLH1基因表达的影响具有浓度依赖性。此外,HSP在BT-549细胞系中对MSH2基因表达具有浓度依赖性影响,但在MCF-10a细胞系中没有。流式细胞术分析表明,细胞死亡和早期凋亡的浓度依赖于HSP的应用。与正常细胞系相比,HSP引起细胞凋亡的能力及其对恶性细胞系的更强影响表明,它可能是对抗癌症的有效治疗方法。
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来源期刊
CiteScore
2.00
自引率
7.10%
发文量
44
审稿时长
20 weeks
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.
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