Abstract 4083: Basic mechanisms of Vernonia amygdalina exert antitumor activities in breast cancer cells

Abstract

Abstract Breast cancer continues to represent the largest cause of mortality in the world especially among women. It is estimated that cancer kills more women in the USA than any other illness and it is also the leading cause of death among all Americans. Traditional medicine represents the first-choice of healthcare treatment for at least 80% of people living in developing countries. Preliminary studies from our laboratory have shown that a novel natural product, extracts of Vernonia amygdalina (VA) leaf exerts DNA-damaging anticancer activities against breast cancer. There is a need to develop targeted approaches for the treatment of human breast cancer. Therefore, the goal of this research was to determine the therapeutic mechanisms of V. amygdalina leaf extracts as anti-cancer agent in the management of breast cancer. To achieve our goal, cell viability, live and death cells were determined by trypan blue exclusion test. The extent of oxidative cell/tissue damage was determined by measuring malondialdehydes (MDA) levels. Expression of p53 tumor suppressor gene was assessed both by immunofluorescent and western blot analyses. Cell apoptosis was measured both by flow cytometry analysis and DNA laddering assay. Data obtained from the Trypan blue indicated that V. amygdalina significantly reduced the viability of MCF-7 cells in a dose-dependent response, showing gradual increase in the loss of viability in V. amygdalina-treated cells due to membrane damage. We observed an up-regulation of p53 tumor suppressor gene in V. amygdalina-treated cells compared to the control. Flow cytometry data showed a strong dose-response relationship between V. amygdalina exposure and caspase-3 positive cells. These results were confirmed by data of DNA laddering assay showing a clear evidence of nucleosomal DNA fragmentation in V. amygdalina-treated cells. Collectively, data generated from the present study demonstrated that V. amygdalina destroys breast cancer cells by reducing the percentage of cell viability and inducing apoptosis through up-regulation of p53 tumor suppressor gene, activation of caspase-3, and induction of nucleosomal DNA fragmentation associated with the formation of MDA, a by-product of lipid peroxidation and biomarker of oxidative stress. This result suggests that V. amygdalina treatment may be a good anti-cancer candidate for the treatment of breast cancer. Research supported by NIH Grant No. NIMHDG12MD007581) Citation Format: Clement G. Yedjou, Paul B. Tchounwou. Basic mechanisms of Vernonia amygdalina exert antitumor activities in breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4083. doi:10.1158/1538-7445.AM2017-4083