Rosmarinic acid failed to suppress hydrogen peroxide-mediated apoptosis but induced apoptosis of Jurkat cells which was suppressed by Bcl-2.
Rosmarinic acid (RosA), frequently found as a secondary metabolite in herbs and medicinal plants, has exhibited antioxidative and anti-inflammatory activities. RosA was shown to inhibit the proliferation and induce apoptosis of Jurkat T cells but the mechanism of action of RosA in apoptosis remains elusive. RosA inhibited the proliferation of Jurkat cells in a dose-dependent manner by suppressing the expression of cyclin D3 and p21(Cip1/Waf1) and up-regulating p27(Kip1). RosA induced apoptosis of Jurkat cells in a dose-dependent manner and failed to protect them from hydrogen peroxide (H2O2)-mediated apoptosis. Induction of apoptosis by RosA correlated with suppression of Bcl-2 but not of Bak or PUMA. Overexpression of Bcl-2 protected Jurkat cells from both H2O2- and RosA-induced apoptosis by altering the ratio of anti- to pro-apoptotic members of the Bcl-2 family. In conclusion, RosA inhibited Jurkat cell proliferation by altering the expression of cyclins and cyclin-dependent kinase inhibitors and induced apoptosis most likely acting through the mitochondrial pathway and possessed no anti-oxidant properties.
Kolettas
Evangelos
E
Cell and Molecular Physiology Unit, Laboratory of Physiology, School of Medicine, University of Ioannina, 45110, Ioannina, Greece. ekoletas@cc.uoi.gr
Thomas
Christoforos
C
Leneti
Eleni
E
Skoufos
Ioannis
I
Mbatsi
Christina
C
Sisoula
Christina
C
Manos
George
G
Evangelou
Angelos
A
D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002934:Cinnamates / Q000494:pharmacology*; D053630:Depsides; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D019169:Jurkat Cells / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D000097123:Rosmarinic Acid
D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D002934:Cinnamates; D053630:Depsides; D006861:Hydrogen Peroxide; D019253:Proto-Oncogene Proteins c-bcl-2; D000097123:Rosmarinic Acid