Exp Mol Med.  2008 Oct;40(5):486-494. 10.3858/emm.2008.40.5.486.

Inhibitory effect of capsaicin on B16-F10 melanoma cell migration via the phosphatidylinositol 3-kinase/Akt/Rac1 signal pathway

• Shin DH
• Kim OH
• Jun HS
• Kang MK

• KMID: 1104802
• DOI: http://doi.org/10.3858/emm.2008.40.5.486

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.

Keyword

capsaicin; cell migration inhibition; cell movement; melanoma; 1-phosphatidylinositol 3-kinase; proto-oncogene proteins c-akt; rac1 GTP-binding protein

MeSH Terms

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