Ursolic acid induces apoptosis through caspase-3 activation and cell cycle arrest in HaCat cells.
Ursolic acid (UA) is a pentacyclic triterpene compound isolated from many kinds of medicinal plants and present in human diet. In this study, we investigated the pro-apoptotic effect of UA on HaCat derived keratinocyte cell line. Treatment with UA decreased the viability of HaCat cells in a concentration- and time-dependent manner. In addition, cell cycle analysis revealed that UA treated HaCat cells were blocked predominantly in G1 phase. Moreover, expression of p21WAF1, a cell cycle regulator, was increased by UA, indicating that UA-induced cell cycle arrest could be mediated through p21WAF1. During UA treatment, we also demonstrated that p53 was phosphorylated at serine 392 and translocated to the nucleus. It is well established that p53 achieves its tumor suppressor activity by inducing apoptosis on cells. To define the apoptotic process in our system, we examined effect of UA on caspase activities, and demonstrated caspase-3 activation. In conclusion, our results suggest that UA induces: i) cell cycle arrest concomitantly with the apparition of the apoptotic sub group G1 peak, and ii) cell death through apoptosis, which is mediated by caspase-3.
Harmand
Pierre-Olivier
PO
Laboratoire de Chimie-Physique, UPRES EA 1085, Faculté de Pharmacie, 2 rue du Docteur Marcland, 87025 Limoges Cedex, France.
Duval
Raphael
R
Liagre
Bertrand
B
Jayat-Vignoles
Chantal
C
Beneytout
Jean-Louis
JL
Delage
Christiane
C
Simon
Alain
A
D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002384:Catalysis; D002453:Cell Cycle; D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D004396:Coloring Agents / Q000494:pharmacology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D016193:G1 Phase; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D010766:Phosphorylation; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012694:Serine / Q000737:chemistry; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D014315:Triterpenes / Q000378:metabolism*; D014343:Trypan Blue / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D000097245:Ursolic Acid
D053148:Caspase 3; D020169:Caspases; D004396:Coloring Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D012313:RNA; D012694:Serine; D013778:Tetrazolium Salts; D013844:Thiazoles; D014315:Triterpenes; D014343:Trypan Blue; D016159:Tumor Suppressor Protein p53; D000097245:Ursolic Acid; C493956:CDKN1A protein, human; C505407:CASP3 protein, human; C022616:thiazolyl blue