The extract of Glycyrrhiza uralensis Fisch induces apoptosis in MGC-803 cells and its molecular mechanisms

Glycyrrhiza uralensis Fisch has been used as an antidote, anti-inflammatory, demulcent and elixir folk medicine for generations in China. The present study demonstrates for the first time that the extract of glycyrrhiza uralensis Fisch (EGUF) induces apoptosis in human gastric cancer cell line MGC-803 as determined by fluorescence microscope, flow cytometry, DNA agarose gel electrophoresis and TUNEL assay. We also report here the up-regulation of two oncogenes, c-myc and c-jun, in the treated cells using RT-PCR and immunohistochemistry assay. By flow cytometry, measurements with the Ca2+-sensitive dye Fluo-3-AM revealed significant enhancement of intracellular Ca2+ content in a dose-dependent manner following the treatment with EGUF. Increased activity of protein kinase C (PKC) in MGC-803 exposed to EGUF was also investigated. In addition, pretreatment of MGC-803 cells with staurosporine (a PKC inhibitor) or PMA (a PKC activator) significantly suppressed or boosted apoptosis induced by EGUF respectively. These findings suggest that glycyrrhiza uralensis Fisch may be a potential, natural apoptosis-inducing agent for gastric cancer therapy and the increase of Ca2+-dependent PKC activity plays a critical role in the apoptotic process induced by EGUF.