Cancer is an enormous burden of disease globally. Today, more people die from cancer than a combination of several diseases. And in females, breast and cervical malignancies remain the most common types. Currently, cervical and breast cancer are the most diagnosed gynecological cancer type amongst black females in the Southern Sahara while amongst males prostate cancer is on the upward trend. With many of them still dependent on medicinal plants as a form of therapy and the need to identify new therapeutic agents, we have identified a commonly used medicinal plant Tulbaghia violacea Harv. commonly known as Itswele lomlambo (Xhosa), wilde knoffel (Afrikaans) and Isihaqa (zulu) to evaluate its anticancer properties at a molecular biology level. In this study, we evaluated the molecular mechanism of T. violacea extracts in regulating cell death in various cancer cell lines. To achieve this, T. violacea was collected, dried before crushing into a fine ground powder. Three organic solvents namely, methanol, hexane, and butanol at 10 g per 100 mL were used as extraction solvents. Each cell line was treated with varying concentrations of the plant extract to identify the half-maximal inhibitory concentration (IC50). The IC 50 was later used to analyse if the extracts were inducing apoptosis using annexin V analysis. Furthermore, the molecular mechanisms by which apoptosis was induced was analysed by qPCR, western blots. All three extracts exhibited anticancer activity with the most cytotoxic being methanol extract. p53 expression was significantly increased in treated cells that correlated with increased caspase activity. The results point to possible activation of apoptosis following treatment with hexane extracts.

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Gynaecological cancers are increasingly becoming the cause of death in females in developing countries. This type of cancers, especially cervical cancer is in the increase due to co-infection with HIV. Many of these people are solely dependent on traditional remedies, as conventional treatment might be expensive or inaccessible to them. In this study we characterised butanolic, hexane and methanolic extracts of Euphorbia tirucalli using both TLC and LC-MS spectroscopy. Following extract analysis, we looked at the effects of the extracts in regulating cell death in breast (MDA-MB 231), ovarian (RMG-1) and cervical (SiHa) cancer cell lines. The cells were treated with varying concentrations of the cocktailed extracts for up to 48 hours. A real time cell analyzer (xCELLigence) was used to monitor cell growth and to determine IC50. MTT assay was used to assess cell viability 24 hours post treatment with extracts. To determine if the extracts had an effect on cell cycle arrest, cell cycle distribution was determined by staining treated cancer cells with propidium iodide and the percentages of G0/G1, S, G2/M cell populations were analysed using flow cytometry. To determine the type of cell death induced, flow cytometry using annexin V was employed. At IC50, molecular analysis was performed to evaluate the effect cocktailed extracts had on apoptotic and cell cycle genes. Cocktailed extracts were found to inhibit cell proliferation in a concentration and cell type dependent manner. Cells were also found to have been arrested at G0/G1 and in some cases apoptosis induced. In general most pro-apoptotic genes like Bax and caspase-8 were upregulated this included the cell cycle gene p21 which was found to be significantly up-regulated in cells treated with extracts. These results suggest that the 3 cocktailed extracts might induce apoptosis or arrest cells at G0/G1 with the molecular mechanism that suggest activation of caspase-8 and Bax. Note: This abstract was not presented at the meeting. Citation Format: Mpho Choene, Lesetja Motadi. Role of Euphorbia tirucalli terpenes cocktail extracts in the regulation of molecular cell death: implications in gynecological cancer progression. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1786. doi:10.1158/1538-7445.AM2015-1786

Breast carcinoma represents the second leading cause of cancer death in developed countries amongst women. Current cytotoxic chemotherapy plays an important role in the management of patients with hormone-insensitive or metastatic breast carcinoma, although most of them ultimately develop recurrences. Therefore, there is a need for novel targets and treatment strategies in patients with advanced breast carcinoma that is refractory to conventional chemotherapy. This paper summarizes current knowledge on breast cancer targets and molecular mechanisms that follows apoptosis induction.

Background Natural compounds derived from various medicinal plants may activate several physiological pathways which can be valuable to diseases such as cancer. Isomukaadial acetate has previously been shown to possess antimalarial and anti-diabetic properties. The purpose of this study was to evaluate the antiproliferative effects of isomukaadial acetate on breast and ovarian cancer cell lines. Method Cell viability assays were conducted using AlamarBlue assay and xCELLigence system. Cell apoptosis and cell cycle arrest were determined and analyzed by ow cytometer. caspase (3/7) activation was evaluated by caspase Glo®-3/7 reagent and gene expression was analyzed by Real-Time Polymerase Chain Reaction. Results The Alamar blue assay and xCELLigence showed that Isomukaadial acetate exhibited anti-proliferative effects on MDA-MB 231, RMG-1, and HEK 293 cell lines in a concentration-dependent manner. Iso-mukaadial acetate induced apoptosis in both cancer cell lines caused cell cycle arrest at the S phase (RMG-1) and early G2 phase (MDA-MB 231) and expressed caspase 3/7 activity in MDA-MB 231 and RMG-1 cells. BAX and p21 were upregulated in MDA-MB 231 and RMG-1 cells after treatment. Conclusion IMA signi cantly inhibited cancer growth and induced cell apoptosis with cell cycle modulation. IMA may be considered a promising candidate for the development of anticancer drugs either for its cytotoxic or cytostatic effect Furthermore, IMA requires to be further studied more to clearly understand its mechanism of action on cancer cells.