Korean J Otolaryngol-Head Neck Surg.
2006 Dec;49(12):1181-1187.
Mechanism of Apoptosis Induced by Ginkgo Biloba Extract(Egb 761) in Oral Cavity Cancer Cell Lines
- Affiliations
-
- 1Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Korea. ydrhinol@yumc.yonsei.ac.kr
- 2The Airway Mucus Institute, Yonsei University College of Medicine, Seoul, Korea.
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.