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 urale nsis Fisch (EGUF) induces apoptosis in human gastric cancer cell line MGC-8 03 as determined by fluorescence microscope, flow cytometry, DNA agarose ge l 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 immu nohistochemistry assay. By flow cytometry, measurements with the Ca2+-sensi tive dye Fluo-3-AM revealed significant enhancement of intracellular Ca2+ c ontent in a dose-dependent manner following the treatment with EGUF. Increa sed 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 boo sted apoptosis induced by EGUF respectively. These findings suggest that gl ycyrrhiza uralensis Fisch may be a potential, natural apoptosis-inducing ag ent for gastric cancer therapy and the increase of Ca2+-dependent PKC activ ity plays a critical role in the apoptotic process induced by EGUF.