구강암종 세포주에서 은행잎 추출물(EGb761)에 의한 세포고사 기전

Abstract

Background and Objectives : According to our previous study Ginkgo biloba extract (EGb 761) induces inhibition of cell proliferation and apoptosis in SCC 1483 oral cavity cancer cells. On the other hand, in lipopolysaccharide-stimulated RAW 264.7 cells, activation of mitogen activated protein kinase (MAPK) is the key event in the inhibition of inflammation by EGb 761. Therefore, we have investigated whether MAPK pathway is involved in the apoptotic process by EGb 761 in oral cavity cancer cell lines or not.

Subjects and Method : In SCC 1483 oral cavity cancer cell lines, Western blot analysis, Fluorescence-activated cell sorter (FACS) analysis, and transient transfection using MAPK-dominant negative constructs were used.

Results : When SCC 1483 oral cavity cancer cell lines were treated with the concentration of 250 microgram/ml EGb 761, activation of extracellular signal-regulated kinase (ERK) and apoptosis were noted. This apoptosis was inhibited by the treatment with ERK inhibitor (PD 98059). In the transiently transfected cells by MAPK/ERK kinase 1 (MEK1)-dominant negative construct, phosphorylations of ERK and p90 ribosomal S 6 protein kinase (RSK1) were inhibited which led to the inhibition of apoptosis by EGb 761. The inhibition of apoptosis was also noted in the transfected cells by RSK1 dominant negative construct and cAMP response element binding protein (CREB)-dominant negative construct.

Conclusion : In conclusion, the apoptosis of SCC 1483 oral cavity cancer cell lines by EGb 761 is linked to the activation of ERK and it can happen via ERK MAPK/RSK1/CREB signal transduction pathway.