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Title: Inhibition of NF-kB-mediated Transcription and Induction of Apoptosis in Human Breast Cancer Cells by Epoxypseudoisoeugenol-2-methyl butyrate

Author
item MA, GUOYI - UNIVERSITY OF MISSISSIPPI
item Tabanca, Nurhayat
item BASER, K. HUSNU CAN - Anadolu Universtiy
item KIRIMER, NESE - Anadolu Universtiy
item PASCO, DAVID - University Of Mississippi
item KHAN, IKHLAS - University Of Mississippi
item KHAN, SHABANA - UNIVERSITY OF MISSISSIPPI

Submitted to: Cancer Chemotherapy and Pharmacology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/5/2008
Publication Date: 1/22/2009
Citation: Ma, G., Tabanca, N., Baser, K., Kirimer, N., Pasco, D.S., Khan, I.A., Khan, S.I. 2009. Inhibition of NF-kB-mediated Transcription and Induction of Apoptosis in Human Breast Cancer Cells by Epoxypseudoisoeugenol-2-methyl butyrate. Cancer Chemotherapy and Pharmacology. 63:673-680.

Interpretive Summary: Breast cancer is a leading cause of morbidity and mortality in women in developed as well as in developing countries. Breast cancer cells contain high levels of nuclear factor kappa B (NF-kB) DNA-binding activity, which is essential for the survival of these cells in culture. High levels of activated NF-kB are also associated with the progression of breast cancer cells from estrogen-dependent phenotype to estrogen-independent phenotype. Inhibition of NF-kB may have a therapeutic potential for control of breast cancer progression and NF-kB may be a molecular target for breast cancer chemotherapy. In the present study, a compound named epoxypseudoisoeugenol-2-methyl butyrate, from the herbal plant Pimpinella corymbosa, inhibited NF-kB-mediated gene expression in hormone-dependent human breast cancer cells.

Technical Abstract: Breast cancer is one of the most prevalent woman cancers. Genomic instability, accumulative mutations, and subsequent changes in intracellular signaling cascades play key roles in the development of human breast cancers. Activation of nuclear factor-kB (NF-kB) has been implicated in oncogenesis of breast cancers and is known to be associated with resistance to anticancer agents and apoptosis. Blocking NF-kB signaling may represent a therapeutic strategy in breast cancer therapy. In present study, the effects of epoxypseudoisoeugenol-2-methyl butyrate (EPB), a phenylpropranoid isolated from Pimpinella corymbosa, on the activation of NF-kB, cell growth, cell cycle progression and apoptosis were investigated in MCF-7 (estrogen-dependent) and BT 549 (estrogen-independent) breast cancer cells. EPB inhibited the NF-kB-mediated transcription activity induced by tumor necrosis factor-a (TNF-a) and phorbol myristate acetate (PMA) in MCF-7 cells. EPB also inhibited constitutive NF-kB transcriptional activity in BT 549 cells. EPB inhibited the proliferation of both MCF-7 and BT-549 cells in a concentration- and time-dependent manner. Cell cycle analysis and DAPI staining indicated that EPB induced cell cycle arrest in G1/G0 phase and apoptosis in both MCF-7 and BT 549 cells. These results indicated that EPB has a potential for use against both hormone-dependent and hormone-independent breast cancers by inhibiting the NF-kB activity.