Rugosin E, an ellagitannin, inhibits MDA-MB-231 human breast cancer cell proliferation and induces apoptosis by inhibiting nuclear factor-kappaB signaling pathway.

Abstract

In this study, we first report the chemopreventive effect of rugosin E in human breast cancer cell line, MDA-MB-231. Treatment with rugosin E decreased the cell proliferation of MDA-MB-231 cells in a dose-dependent manner. Rugosin E treatment arrested MDA-MB-231 cells at G0/G1 phase. This effect was strongly associated with concomitant decrease in the level of cyclin D1, cyclin D2, cyclin E, cdk2, cdk4, and cdk6, and increase of p21/WAF1. In addition, rugosin E also induced apoptotic cell death. Rugosin E increased in the expression of Bax, Bak, and Bcl-Xs, but decreased the levels of Bcl-2 and Bcl-X(L), and subsequently triggered mitochondria apoptotic pathway (release of cytochrome c, activation of caspase-9, and caspase-3). In addition, pre-treatment of cells with caspase-9 inhibitor blocked rugosin E-induced cell proliferation and apoptosis, indicating caspase-9 activation was involved in rugosin E-mediated MDA-MB-231 cells apoptosis. Rugosin E inhibited the constitutively activated and inducible NF-kappaB in both its DNA-binding activity and transcriptional activity. Furthermore, rugosin E also inhibited the TNF-alpha-activated NF-kappaB-dependent reporter gene expression of cyclin D1, c-Myc, XIAP, Bcl-2, and Bcl-X(L) were all downregulated by rugosin E. Our results indicated that rugosin E inhibits the activation of NF-kappaB, and this may provide a molecular basis for drug development in the prevention and treatment of cancer by rugosin E.

• Authors: Po-Lin Kuo, Ya-Ling Hsu, Ta-Chen Lin, Wen-Sheng Tzeng, Yin-Yi Chen, Chun-Ching Lin
• Journal: Cancer letters (Cancer Lett) Vol. 248 Issue 2 Pg. 280-91 (Apr 18 2007) ISSN: 0304-3835 [Print] Ireland
• PMID: 16963181 (Publication Type: Journal Article)

Chemical References

• Cell Cycle Proteins
• Hydrolyzable Tannins
• NF-kappa B
• rugosin E

Topics

• Apoptosis (drug effects)
• Blotting, Western
• Breast Neoplasms (metabolism, prevention & control)
• Cell Cycle (drug effects)
• Cell Cycle Proteins (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Electrophoretic Mobility Shift Assay
• Female
• Humans
• Hydrolyzable Tannins (pharmacology)
• NF-kappa B (drug effects, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction (drug effects)