Inhibitory effect of capsaicin on B16-F10 melanoma cell migration via the phosphatidylinositol 3-kinase/Akt/Rac1 signal pathway.
10.3858/emm.2008.40.5.486
- Author:
Dong Hoon SHIN
1
;
Ok Hee KIM
;
Hye Seung JUN
;
Mi Kyung KANG
Author Information
1. Department of General Surgery, Kosin University College of Medicine, Busan, Korea.
- Publication Type:Original Article
- Keywords:
capsaicin;
cell migration inhibition;
cell movement;
melanoma;
1-phosphatidylinositol 3-kinase;
proto-oncogene proteins c-akt;
rac1 GTP-binding protein
- MeSH:
1-Phosphatidylinositol 3-Kinase/*metabolism;
Animals;
Capsaicin/*pharmacology;
Cell Line, Tumor;
Cell Movement/*drug effects;
Cell Survival/drug effects;
Dose-Response Relationship, Drug;
Immunoblotting;
Melanoma, Experimental/metabolism/pathology/physiopathology;
Mice;
Proto-Oncogene Proteins c-akt/*metabolism;
Signal Transduction/*drug effects;
rac1 GTP-Binding Protein/*metabolism
- From:Experimental & Molecular Medicine
2008;40(5):486-494
- CountryRepublic of Korea
- Language:English
-
Abstract:
Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide), the major pungent ingredient of red pepper, has been reported to possess anti-carcinogenic and anti-mutagenic activities. In this study, the anti-migration activity of capsaicin on highly metastatic B16-F10 melanoma cells was investigated. Capsaicin significantly inhibited the migration of melanoma cells without showing obvious cellular cytotoxicity at low doses. This effect correlated with the down-regulation of phosphatidylinositol 3-kinase (PI3-K) and its downstream target, Akt. Although B16-F10 cell migration was increased by the PI3-K activator through the activation of Akt, these PI3-K activator-induced phenomena were attenuated by capsaicin. Moreover, capsaicin was found to significantly inhibit Rac1 activity in a pull-down assay. These results demonstrate that capsaicin inhibits the migration of B16-F10 cells through the inhibition of the PI3-K/Akt/Rac1 signal pathway. The present investigation suggests that capsaicin targets PI3-K/Akt/ Rac1-mediated cellular events in B16-F10 melanoma cells. Consequently, capsaicin administration should be considered an effective approach for the suppression of invasion and metastasis in malignant melanoma chemotherapy.