Exploring the modulation of MLH1 and MSH2 gene expression in hesperetin-treated breast cancer cells (BT-474).

The major mortality factor for women globally is breast cancer, and current treatments have several adverse effects. Hesperetin (HSP) is a flavone that occurs naturally with anti-tumor capabilities and has been investigated as a potential treatment for cancer. This study aimed to investigate the cytotoxic and anti-malignant potential of HSP on breast cancer cells (BT-474) and normal cells (MCF-10a). The results indicated that HSP has dose-dependent cytotoxicity in BT-474 and MCF-10a cells. The elevated concentration of HSP lowered cell viability and proliferation. The half-maximal inhibitory concentration (IC50) of HSP in BT-474 cancer cells after a 48-h exposure was 279.2 µM/ml, while the IC50 in normal cells was 855.4 µM/ml. The cytotoxicity of HSP was more significant in cancer cell lines than in normal cell lines and this aspect presents a favorable factor in utilizing the drug for the treatment of breast cancer. The apoptotic effect of HSP in BT-474 cells was investigated, and it was found that the higher the concentration of HSP more the cells underwent apoptosis. Furthermore, the highest concentration of HSP led to overexpression of the MLH1 and MSH2 genes in both breast cancer and normal cell lines. Overall, our study suggests that HSP has an anticancer effect on breast cancer cell lines, and the effect is concentration dependent.

Study of hesperetin effect on modulating transcription levels of MLH1 and MSH2 genes in SKBR3 breast cancer cell line.

Hesperetin (HSP), a flavonoid, has been validated to modify gene expression and function as an epigenetic agent to stop the development of breast carcinoma cells. HSP was investigated in this research to evaluate the expression of the MLH1 and MSH2 genes in cancerous breast cell lines (SKBR3) and healthy cell lines (MCF-11A) after exposure to different dosages (200, 400, and 600 µM/mL) of HSP. After 48 h of exposure, SKBR3's half-maximal inhibitory concentration was 289.6 µM/mL and MCF-10A's was 855.4 µM/mL. The research found that increasing HSP concentrations were closely correlated with an increase in MLH1 gene levels in the SKBR3 cell line, as shown by median and percentile values. HSP therapy caused the MLH1 gene expression to substantially vary in different groups, and in the SKBR3 cell line, MSH2 gene expressions were elevated in a dose-escalating manner. Moreover, HSP also raised the number of apoptotic cells, with the fraction of apoptotic cells escalating substantially at doses of 400 and 600 µM/mL. The outcomes suggested that HSP has the potential to be utilized as a therapeutic intervention for breast cancer, as it can induce apoptosis and reduce cell viability.

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

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.

In Vitro Macrophage Nitric Oxide and Interleukin-1 Beta Suppression by Moringa peregrina Seed.

OBJECTIVES: Moringa peregrina has long been used in folk medicine to treat diseases including fever, headache, burns, constipation, gut pains, and inflammation. Nitric oxide (NO) and interleukin-1ß (IL-1ß) play an important role in the pathophysiology of inflammation. The objectives of this study were to determine the effect of M. peregrina seed ethanolic extract (MPSE) on the viability of and NO and IL-1ß production by lipopolysaccharide (LPS)-activated macrophage (J774A.1) cell line. MATERIALS AND METHODS: The 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide assay was used to determine the cytotoxic effect of MPSE treatment at concentrations ranging from 31.15 to 1000 µg/mL. The NO concentration was determined by Griess assay and IL-1ß proinflammatory cytokine concentration by enzyme-linked immunosorbent assay in the supernatant of MPSE-treated LPS-activated J774A.1 cell culture. RESULTS: The results show that the MPSE was not cytotoxic at 1000 µg/mL but significantly (p<0.001) inhibited NO and IL-1ß production by the LPS-activated macrophage J774A.1 cells. CONCLUSION: These findings suggest that M. peregrina seed extract can be used to treat and prevent inflammatory diseases through the inhibition of inflammatory mediators.