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Ursolic acid induces apoptosis through mitochondrial intrinsic pathway and caspase‐3 activation in M4Beu melanoma cells
Author(s) -
Harmand PierreOlivier,
Duval Raphaël,
Delage Christiane,
Simon Alain
Publication year - 2005
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.20588
Subject(s) - ursolic acid , apoptosis , melanoma , caspase , programmed cell death , mitochondrion , uvb induced apoptosis , skin cancer , cancer research , chemistry , microbiology and biotechnology , intrinsic apoptosis , inner mitochondrial membrane , cancer cell , biology , cancer , biochemistry , genetics , chromatography
Over the coming years, skin cancer could become a significant public health problem. Previous results indicate that ursolic acid (UA), a pentacyclic triterpene acid, has pleiotropic biologic activities such as antiinflammatory and antiproliferative activities on cancer cells. As UA represents a promising chemical entity for the protection of human skin, in agreement with tests done by the cosmetic industry, we investigated its effects on the M4Beu human melanoma cell line. In this report, we demonstrated for the first time that UA had a significant antiproliferative effect on M4Beu, associated with the induction of an apoptotic process, characterized by caspase‐3 activation, the downstream central effector of apoptosis. We demonstrated that UA‐induced apoptosis was dependent on the mitochondrial intrinsic pathway, as shown by transmembrane potential collapse (ΔΨm) and by alteration of the Bax‐Bcl‐2 balance, with a concomitant increase in Bax expression and decrease in Bcl‐2 expression. We also showed that UA‐induced ΔΨm was associated with apoptosis‐inducing factor leakage from mitochondria. Taken together, our results suggest that UA‐induced apoptosis on M4Beu cells is accomplished via triggering of mitochondrial pathway. In conclusion, UA could be an encouraging compound in the treatment or prevention of skin cancer and may represent a new promising anticancer agent in the treatment of melanoma. © 2004 Wiley‐Liss, Inc.