Asiatic acid induces apoptosis in SK-MEL-2 human melanoma cells.
Asiatic acid (AA) is a pentacyclic triterpene found in Centella asiatica. In the present study, the mechanism of anticancer effect of AA on skin cancer was investigated. AA decreased viability and induced apoptosis in human melanoma SK-MEL-2 cells in a time- and dose-dependent manner. AA also markedly increased intracellular reactive oxygen species (ROS) level and enhanced the expression of Bax but not Bcl-2 protein in the cells. In addition, AA-induced activation of caspase-3 activity in a dose-dependent manner. Pretreatment with Trolox, an antioxidant, significantly blocked the induction of Bax and activation of caspase-3 in AA-treated cells. Furthermore, Ac-DEVD-CHO, a specific caspase-3 inhibitor, and Trolox prevented the AA-induced apoptosis. AA did not elevate p53 nuclear protein levels that are present in a mutant form in SK-MEL-2 cells. These results suggest that AA-induced apoptosis may be mediated through generation of ROS, alteration of Bax/Bcl-2 ratio and activation of caspase-3, but p53-independent. These results further suggest that AA may be a good candidate for the therapeutic intervention of human skin cancer.
Park
Byung Chul
BC
College of Pharmacy, Yeungnam University, Gyongsan 712-749, South Korea.
Bosire
Kefa O
KO
Lee
Eung-Seok
ES
Lee
Yong Soo
YS
Kim
Jung-Ae
JA
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000494:pharmacology; D028041:Centella / Q000737:chemistry; D006801:Humans; D008545:Melanoma / Q000473:pathology*; D053978:Pentacyclic Triterpenes; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000494:pharmacology; D017382:Reactive Oxygen Species; D012878:Skin Neoplasms / Q000473:pathology*; D014315:Triterpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D053978:Pentacyclic Triterpenes; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D014315:Triterpenes; D051028:bcl-2-Associated X Protein; C017032:asiatic acid; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases