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

• Published in: Experimental & molecular medicine Vol. 40; no. 5; pp. 486 - 494
• Main Authors: Shin, Dong-Hoon, Kim, Ok-Hee, Jun, Hye-Seung, Kang, Mi-Kyung
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 31.10.2008; Springer Nature B.V; Korean Society of Medical Biochemistry and Molecular Biology; 생화학분자생물학회
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Capsaicin - pharmacology; Cell Line, Tumor; Cell Movement - drug effects; Cell Survival - drug effects; Dose-Response Relationship, Drug; Immunoblotting; Medical Biochemistry; Melanoma, Experimental - metabolism; Melanoma, Experimental - pathology; Melanoma, Experimental - physiopathology; Mice; Molecular Medicine; Original; Phosphatidylinositol 3-Kinases - metabolism; Proto-Oncogene Proteins c-akt - metabolism; rac1 GTP-Binding Protein - metabolism; Signal Transduction - drug effects; Stem Cells; 생화학; cell movement; capsaicin; proto-oncogene proteins c-akt; melanoma; 1-phosphatidylinositol 3-kinase; cell migration inhibition; rac1 GTP-binding protein
• ISSN: 1226-3613; 2092-6413
• DOI: 10.3858/emm.2008.40.5.486

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.