Mitotic Arrest and Apoptosis in Breast Cancer Cells Induced by Origanum majorana Extract: Upregulation of TNF-alpha and Downregulation of Survivin and Mutant p53

作者：Al Dhaheri Yusra; Eid Ali; AbuQamar Synan; Attoub Samir; Khasawneh Mohammad; Aiche Ghenima; Hisaindee Soleiman; Iratni Rabah^*

来源：PLos One, 2013, 8(2): e56649.

DOI：10.1371/journal.pone.0056649

Background: In the present study, we investigated the effect of Origanum majorana ethanolic extract on the survival of the highly proliferative and invasive triple-negative p53 mutant breast cancer cell line MDA-MB-231.
Results: We found that O. majorana extract (OME) was able to inhibit the viability of the MDA-MB-231 cells in a time- and concentration-dependent manner. The effect of OME on cellular viability was further confirmed by the inhibition of colony growth. We showed, depending on the concentration used, that OME elicited different effects on the MDA-MB 231 cells. Concentrations of 150 and 300 mu g/mL induced an accumulation of apoptotic-resistant population of cells arrested in mitotis and overexpressing the cyclin-dependent kinase inhibitor, p21 and the inhibitor of apoptosis, survivin. On the other hand, higher concentrations of OME (450 and 600 mu g/mL) triggered a massive apoptosis through the extrinsic pathway, including the activation of tumor necrosis factor-alpha (TNF-alpha), caspase 8, caspase 3, and cleavage of PARP, downregulation of survivin as well as depletion of the mutant p53 in MDA-MB-231 cells. Furthermore, OME induced an upregulation of gamma-H2AX, a marker of double strand DNA breaks and an overall histone H3 and H4 hyperacetylation.
Conclusion: Our findings provide strong evidence that O. majorana may be a promising chemopreventive and therapeutic candidate against cancer especially for highly invasive triple negative p53 mutant breast cancer; thus validating its complementary and alternative medicinal use.

• 出版日期2013-2-22