Drug treatment of prostate cancer cells using a combination of naturally occurring compounds leads to activation of apoptosis

Chemotherapy often uses a combination of drugs in order to activate apoptosis in cancer cells. Combination drug therapy allows for higher sustained rates of apoptosis due to activation of complimentary mechanisms and a lower likelihood of developing resistance. Chemotherapeutics are often toxic, and lead to organ damage and apoptosis in non‐cancerous cells. Naturally occurring compounds, such as resveratrol (RES), epigallocatechin gallate (EGCG), quercetin and avenanthramides have been identified as activators of apoptosis in cancer cells, but are non‐toxic to non‐tumorigenic cells. Since these compounds activate apoptosis through extrinsic and intrinsic pathways as well as the perforin/granzyme pathway, we have used them in combination to activate apoptosis in prostate cancer cells, and have identified an ideal concentration of these compounds using Response Surface Methodology (RSM) of data collected from cell viability assays (MTT assays). Cells were treated with the optimal combination and immunoblotting techniques were used to identify the pathways activated, and to show biomarkers of apoptosis. Time resolved activation of apoptosis was measured by the use of high resolution respirometry which allowed us to measure decreases in mitochondrial function. These techniques were used to demonstrate that combination drug therapy with these naturally occurring compounds is an effective activator of apoptosis in cancer cell models.