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.
Alternative splicing of mRNA leads to an increase in proteome biodiversity by allowing the generation of multiple mRNAs, coding for multiple protein isoforms of various structural and functional properties from a single primary pre-mRNA transcript. The protein isoforms produced are tightly regulated in normal development but are mostly deregulated in various cancers. In HIV-infected individuals with AIDS, there is an increase in aberrant alternative splicing, resulting in an increase in HIV/AIDS-related cancers, such as Kaposi’s sarcoma, non-Hodgkin’s lymphoma, and cervical cancer. This aberrant splicing leads to abnormal production of protein and is caused by mutations in cis-acting elements or trans-acting factors in angiogenesis-related genes. Restoring the normal regulation of alternative splicing of angiogenic genes would alter the expression of protein isoforms and may confer normal cell physiology in patients with these cancers. This review highlights the abnormalities in alternative splicing of angiogenesis-related genes and their implication in HIV/AIDS-related cancers. This allows us to gain an insight into the pathogenesis of HIV/AIDS-related cancer and in turn elucidate the therapeutic potential of alternatively spliced genes in HIV/AIDS-related malignancies.
Cervical cancer, a gynaecological malignant disorder, is a common cause of death in females in Sub-Saharan Africa, striking nearly half a million of lives each year worldwide. Currently, more than 50 % of all modern drugs in clinical use are of natural products, many of which have an ability to control cancer cells (Madhuri and Pandey, Curr Sci 96:779-783, 2009; Richter, Traditional medicines and traditional healers in South Africa, 2003). In South Africa, plants used to treat cancer are rare even though majority of our population continue to put their trust in traditional medicine. In this study we aimed to screen Agave palmeri (AG) and Tulbaghia violacea (TV) for potential role in inducing cell death in cervical cancer cell lines HeLa and ME-180, and in normal human fibroblast cell line KMST-6 cell lines. To achieve this, AG and TV crude extracts were utilized to screen for apoptosis induction, inhibition of cell proliferation followed by elucidation of the role of Bax, Bcl-2, p53, Rb, RBBP and Mdm2 genes in cervical cancer. In brief, plant leaves and roots were collected, crushed and methanolic extracts obtained. Different concentrations of the stock extracts were used to treat cancer cells and measure cell death using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay and flow cytometry. Western blot was applied to measure gene expression at protein level using RBBP6, p53, Mdm2, Rb, Bax, Bcl-2 and β-actin mouse monoclonal primary antibodies (IgG) and goat anti mouse coupled with horseradish peroxidase secondary antibody from Santa Cruz Biotechnology and real time-PCR was used for mRNA expression level. Plant extracts of AG and TV were time (24 h) and dose (50, 100, 150 μg/ml) dependent in their induction of cell death with an IC50 ~ 150 μg/ml. A further mixed respond by several genes was observed following treatment with the two plant extracts where RBBP6 was seen to be spliced in cancer cells while Bax was induced and Bcl-2 was inhibited with the levels of p53 remaining the same. The two plant extracts do induce cell death, in a p53 independent manner.
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.
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