Mitotic Arrest and Apoptosis in Breast Cancer Cells Induced by Origanum majorana Extract: Upregulation of TNF-α and Downregulation of Survivin and Mutant p53
| Autor: | Ali H. Eid, Samir Attoub, Synan F. AbuQamar, Soleiman Hisaindee, Yusra Al Dhaheri, Rabah Iratni, Ghenima Aiche, Mohammad A. Khasawneh |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
cell division
Survivin Cancer Treatment lcsh:Medicine Apoptosis Biochemistry Inhibitor of Apoptosis Proteins Histones Breast cancer Origanum Drug Discovery Molecular Cell Biology lcsh:Science Cellular Stress Responses education.field_of_study Multidisciplinary Cell Death Cell cycle Cell biology Gene Expression Regulation Neoplastic Oncology Cancer treatment Cell cycle inhibitors Medicine Female Cell Division Research Article Drugs and Devices Drug Research and Development Cell Survival Population Mitosis Caspase 3 Breast Neoplasms Biology Inhibitor of apoptosis Caspase 8 Cell Growth Downregulation and upregulation Complementary and Alternative Medicine Cell Line Tumor Humans education Ethanol Plant Extracts Tumor Necrosis Factor-alpha lcsh:R Proteins Regulatory Proteins Ethnopharmacology Cancer research DNA damage lcsh:Q Tumor Suppressor Protein p53 |
| Zdroj: | PLoS ONE PLoS ONE, Vol 8, Iss 2, p e56649 (2013) |
| ISSN: | 1932-6203 |
| Popis: | 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 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. Faculty of Science interdisciplinary research grant UAE University and by the Emirates Foundation research grant (2009-80) Scopus |
| Databáze: | OpenAIRE |
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