OBJECTIVEThis study aimed to discover the cytotoxic effect of YH239-EE and YH239 alone and their enantiomer potency in cytotoxic effect on the MCF7 cell line.METHODSWe used the cytotoxic study on MDM2 cell lines by detecting the percentage of apoptosis and necrosis by annexin v methods.RESULTThis result shows that YH239-EE causes more apoptosis and necrosis 40% in comparison to YH239 without ethyl ester, about 4.92 %, and The (+) enantiomer of YH239-EE demonstrated a markedly higher induction of apoptosis and necrosis (84.48%) in MCF7 cells compared to the (-) enantiomer (48.71%).CONCLUSIONThe ethyl ester group in YH239-EE might play a crucial role in enhancing the compound's ability to induce cell death, and The high efficacy of the (+) enantiomer of YH239-EE in inducing cell death in MCF7 cells suggests it may be a more promising therapeutic candidate for breast cancer treatment, specifically for subtypes represented by MCF7 cells.

01 Jan 2024·Bratislava Medical Journal

Effects of Mdm2 Inhibitors on Cellular Viability of Breast Cancer Cell Lines HP100, MCF7

Article

Author: J AL-ZOBAIDY, Mohammed ; AL-HUSSANIY, Hany Akeel ; J AL-ZOBAIDY, Mohammed ; AL-HUSSANIY, Hany Akeel

BACKGROUNDBreast cancer is one of the main Cancers affecting patients all over the world; however, till now, there has been no successful treatment without any side effects on patient health, but there are groups of medications similar to MDM2 inhibitors that have promising effects. The aim of this study was to find out whether the use of mdm2 inhibitors can help treat breast cancer using three cell lines. The use of treatments belonging to the MDM2 inhibitor alone or with the use of doxorubicin together with a combination of Nutlin-3, Miladometan, Yh239-EE, and doxorubicin in breast cancer cell lines HP100, MCF7.MATERIALS AND METHODSCell lines were treated with different concentrations of MDM2 inhibitors 1,5,10, and 20 micromolar alone or in combinations with doxorubicin. After that, cell viability was estimated by the MTT assay method. Then, we have assessed the expression of caspase as an indicator of cell apoptosis after treatment, and the expression of P53 and MDM2 after and before treatment.RESULTSThe IC50 of Doxorubicin in the MCf7 cell line was about 1.12 µM. The best IC50% in MDM2 inhibitors was for Nutlin, about 5.9 µM, then for Yh239-EE about 8.45 µM, and Milademetan about 11.07 µM the high IC50% values in normal epithelial cell HBl100. Also, the MDM2 inhibitor increased P53 levels, as did doxorubicin.CONCLUSIONOur research concluded that Nutlin 3 has a superior effect over Yh239-EE and Miladometan in treating Breast cancer; moreover, the combination group has shown to be more effective than treatment with Doxorubicin or MDM2 inhibitors alone. Interesting information is that Doxorubicin also causes an increase in P53 levels. This result provided us with a promising therapeutic strategy for the treatment of breast cancer. However, more research is required to be conducted on more types of cell lines and in human or animal models (Tab. 4, Fig. 8, Ref. 33). Text in PDF www.elis.sk Keywords: breast cancer, Miladometan, cell viability, proliferation, therapeutic strategy.

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Indication	Highest Phase	Country/Location	Organization	Date
Acute Myeloid Leukemia	Preclinical	US	University of Pittsburgh	17 Jan 2014

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