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AuthorAl Dhaheri, Yusra
AuthorEid, Ali
AuthorAbuQamar, Synan
AuthorAttoub, Samir
AuthorKhasawneh, Mohammad
AuthorAiche, Ghenima
AuthorHisaindee, Soleiman
AuthorIratni, Rabah
Available date2016-03-31T14:00:59Z
Publication Date2013-02
Publication NamePLoS ONE
ResourceScopus
CitationAl Dhaheri Y, Eid A, AbuQamar S, Attoub S, Khasawneh M, Aiche G, et al. (2013) Mitotic Arrest and Apoptosis in Breast Cancer Cells Induced by Origanum majorana Extract: Upregulation of TNF-α and Downregulation of Survivin and Mutant p53. PLoS ONE 8(2): e56649. 
ISSN1932-6203
URIhttp://dx.doi.org/10.1371/journal.pone.0056649
URIhttp://hdl.handle.net/10576/4306
AbstractBackground: 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 μg/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 μg/mL) triggered a massive apoptosis through the extrinsic pathway, including the activation of tumor necrosis factor-α (TNF-α), 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 γ-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.
SponsorFaculty of Science interdisciplinary research grant UAE University and by the Emirates Foundation research grant (2009-80)
Languageen
PublisherPublic Library of Science
SubjectApoptosis
Cell cycle
cell division
Cancer treatment
Breast cancer
Histones
DNA damage
Ethanol
Cell cycle inhibitors
TitleMitotic Arrest and Apoptosis in Breast Cancer Cells Induced by Origanum majorana Extract: Upregulation of TNF-α and Downregulation of Survivin and Mutant p53
TypeArticle
Issue Number2
Volume Number8
dc.accessType Open Access


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