Abstract
BackgroundIn 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.ResultsWe 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.ConclusionOur 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.
Highlights
Breast cancer is the most frequently diagnosed cancer among women and ranks second as a cause of cancer death in women after lung cancer
We examined the effects of O. majorana extract (OME) on cell viability, cell cycle, apoptosis, and the levels of several cell cycle and apoptosis control proteins in the highly proliferative and invasive Estrogen Receptor (ER)negative, mutant p53 breast cancer cell lines MDA-MB-231
To examine the anticancer activity of Origanum majorana extract (OME) on breast cancer cells, we first measured the effect of various concentrations of the extract (0, 50, 150, 300, 450 and 600 mg/mL) on the proliferation of the MDA-MB-231 breast cancer cell line (Figure 1A)
Summary
Breast cancer is the most frequently diagnosed cancer among women and ranks second as a cause of cancer death in women after lung cancer. An estimated 226,870 new cases of invasive breast cancer are expected to occur among women in the US during 2012 [1]. Plants have been shown to be an excellent source of new drugs, including anticancer agents. Identification and development of new chemotherapeutic agents from plants have gained significant recognition in the field of cancer therapy and become a major area of experimental cancer research. The majority of the chemotherapeutic drugs used in cancer treatment, is either from plant origin or chemically-altered plant products and phytochemicals [2]. Examples of anticancer drugs derived from plants and currently in clinical use include the vinca alkaloids vinblastine and vincristine were isolated from Catharan roseus, the terpene paclitaxel from Taxus brevifolia Nutt., and the DNA topoisomerase I inhibitor camptothecin from Camptotheca acuminata [3]. 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
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