Abstract 5552: Medicinal plants show anticancer splicing activity of apoptotic genes

Abstract

Abstract Oncogenesis is associated with splicing switches and a disruption of splicing regulation being specific for cancer formation and tumour progression. An association between differential expression of splicing isoforms and tumour progression has been shown for several proteins, such as MDM2 and survivin. Currently the analysis of cancer-specific alternative splicing is a promising step forward in basic and translational molecular biology. Traditional medicine has a long history and is still the major source of medicine in developing countries. Approximately 70% of the South African population consults traditional healers, perpetuating the need for scientific appraisal of traditional medicine as a means to establish its efficiency and safety Also, pharmacological and phytochemical insights into several plants have led to the discovery of novel chemicals and therefore novel drugs. Alternatively, such novel chemical structures can serve as lead compounds/templates for the design of new drugs. The aim was to ascertain if the South African medicinal plants have anticancer splicing activity. 10c cells were treated with Tulbhaghia violacea and Cotyledon orbiculata, followed by mRNA extraction and RT-PCR. The results showed that Tulbhaghia violacea and Cotyledon orbiculata extracts have anti-cancer splicing activity on the BCLX and the AXL apoptosis genes. Additionally Cotyledon orbiculata extract has an anticancer splicing activity of the angiogenesis gene VEGF165. VEGF Elisa also confirmed the VEGF165 VEGF165b splicing switch. We have shown that South African medicinal plants have anti-cancer splicing activity. The anti-cancer splicing activity of the VEGF gene by Cotyledon orbiculata could mean that this extract has both angiostatic and apoptotic anti-cancer activities. We are continuing to screen more medicinal plants and will select those extracts with anti-cancer splicing activity for further studies. These further studies should identify numerous splicing pathways and completely elucidate the splicing target compounds that may serve as novel anti-cancer drugs or lead compounds. Note: This abstract was not presented at the meeting. Citation Format: Zodwa Dlamini, David Bates. Medicinal plants show anticancer splicing activity of apoptotic genes. [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 5552. doi:10.1158/1538-7445.AM2015-5552