University of Sistan and Baluchestan, Iran
Title: Investigation on the effects of hydroalchoholic extract of Levisticum officinale on cGMP levels and PDE5 gene expression in breast cancer cell lines MCF-7 and MDA-Mb-468
Biography: Ali Shaharki
Increased expression of cyclic guanosine 3′, 5′ monophosphate phosphodiesterase-5 (cGMP-PDEs) mRNAs has been demonstrated in several human carcinomas, including breast carcinoma, pancreatic cancer, bladder cancer, squamous cell carcinoma and prostate cancer, in comparison to adjacent normal tissues. Studies have elucidated that an increase in intracellular cGMP induces apoptosis and decreases cell population growth. Therefore, selective inhibitors of these PDEs might be potential anticancer agents. Previous investigations have demonstrated that Levisticum officinale contains flavonoids and alkaloids compound that are known as antitumoral components. The purpose of this study was to investigate the effect of Levisticum officinale hydroalcoholic extract on phosphodiesterase 5 gene expression, cGMP signaling pathway and its role in inducing apoptosis in the MCF-7(ER+) and in MDA-Mb-468 (triple-negative) cell lines. The mean inhibitory concentration (IC50) of extract was determined in both cell lines using of MTT assay, and the type of cell death was detected by flow cytometry. The expression of PDE5 and cGMP levels was measured by real-time polymerase chain reaction and colorimetric assay, respectively. Treatment with hydroalchoholic extract of Levisticum officinale showed that 200 µg/ml to be the IC50 for both cell lines. 12 hour treatment with IC50 dosage showed a maximum decrease in the PDE5 expression and maximum increase in intracellular cGMP level, although, these effects were more significant in MDA-MB-468. In conclusion, our results showed that hydroalchoholic extract of Levisticum officinale had an anti-proliferative and apoptotic effect in MCF-7 and MDA-Mb-468 targeting PDE5 and cGMP signaling pathway.