Sesquiterpene Lactones Modulated DNA Methylation through Inhibition of DNMTs in Ovarian Cancer Cells

نویسندگان

چکیده

Inappropriate DNA methylation of tumour suppressor genes can affect their expression and function, as such, has been a promising target for anti-cancer therapy. In gynaecological malignancy, ovarian cancer the highest associated rate mortality. This study investigated in vitro cytotoxicity four sesquiterpene lactones (SLs), including dehydroleucodine (Deh), alantolactone (Ala), costunolide (Cos), parthenolide (Pat), effect on cancer. The binding SLs with methyltransferases (DNMTs) were studied using molecular docking. antiproliferative activity was evaluated human cell lines. SL-induced pro-apoptotic cycles enzymatic assays flow cytometry. Global DNMTs by measured ELISA assays. MHL1 PTEN quantified pyrosequencing RT-qPCR, respectively. displayed strong to DNMT1, 3A 3B silico, Deh exhibiting strongest binding. showed order ≈ Ala > Pat Cos, induced apoptosis, arrested cycle at G2/M phase. possessed DNMT inhibitory activity, reduced global gene-specific methylation, increased notable PTEN, which could contribute induction apoptosis death. conclusion, Ala, possess hold exciting potential novel therapeutic agents

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ژورنال

عنوان ژورنال: Pharmacological research

سال: 2022

ISSN: ['2667-1425']

DOI: https://doi.org/10.1016/j.prmcm.2022.100074