Rosmarinic acid failed to suppress hydrogen peroxide-mediated apoptosis but induced apoptosis of Jurkat cells which was suppressed by Bcl-2
- 131 Downloads
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 p21Cip1/Waf1 and up-regulating p27Kip1. 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.
Keywordsrosmarinic acid hydrogen peroxide proliferation apoptosis Bcl-2 members
Unable to display preview. Download preview PDF.
- 4.Palmer HJ, Paulson KE: Reactive oxygen species and antioxidants in signal transduction and gene expression. Nutr Rev 55: 453–361, 1997Google Scholar
- 6.Al-Sereti MR, Abu-Amer KM, Sen P: Pharmacology of rosemary (Rosmarinus officinalis Linn.) and its therapeutic potentials. Indian J Exp Biol 37: 124–130, 1999Google Scholar
- 15.Kim D-S, Kim H-R, Woo E-R, Hong S-T, Chae H-J, Chae S-W: Inhibitory effects of rosmarinic acid on adriamycin-induced apoptosis in H9c2 cardiac muscle cells by inhibiting reactive oxygen species and the activations of c-jun N-terminal kinase and extracellular signal-regulated kinase. Biochem Pharmacol 70: 1066–1078, 2005PubMedCrossRefGoogle Scholar
- 29.Sherr CJ: The Pezcoller Lecture: Cancer Cell Cycles Revisited. Cancer Res 60: 3689–3695, 2000Google Scholar
- 39.Stewart ZA, Leach SD, Pietenpol JA: p21Waf1/Cip1 inhibition of cyclin E/Cdk2 activity prevents enderoduplication after mitotic spindle disruption. Mol Cell Biol 19: 206–215, 1999Google Scholar
- 46.Hildeman DA, Mitchell T, Aronow B, Wojciechowski S, Kappler J, Marrack P: Control of Bcl-2 expression by reactive oxygen species. Proc Natl Acad Sci USA 100: 15035–15040, 2003Google Scholar