Abstract
BackgroundCurrently offered therapeutics to treat colon cancer (CoCa) are toxic when given at maximum tolerated dose to achieve optimal clinical response. Hence, less toxic therapeutic intervention is needed to treat CoCa. In this study, we investigated the effect of a natural agent, Emodin, on CoCa.MethodsCell viability (MTT) assay was used to determine the effect of Emodin on human CoCa and colon epithelial cells. Flow cytometric analysis was used to determine Emodin induced cell death. Antibody microarray and western blot analyses were used to determine Emodin induced molecular changes involved in cell death. Change in mitochondrial membrane potential in response to Emodin was determined by flow cytometric analysis. Expression and localization of Bcl-2 family proteins were assessed by western blot analysis.ResultsEmodin decreased viability of CoCa cells and induced apoptosis in a time and dose-dependent manner compared to vehicle-treated control without significantly impacting normal colon epithelial cells. Emodin activated caspases, modulated Bcl-2 family of proteins and reduced mitochondrial membrane potential to induce CoCa cell death. Further, changes in Bcl-2 family protein expression and localization correlated with loss in mitochondrial membrane potential. Signaling (MAPK/JNK, PI3K/AKT, NF-κβ and STAT) pathways associated with cell growth, differentiation, and Bcl-2 family expression or function were negatively regulated by Emodin.ConclusionsAbility of Emodin to impact molecular pathways involved in cell survival and apoptosis highlight the potential of this agent as a new and less toxic alternative for CoCa treatment.
Highlights
Offered therapeutics to treat colon cancer (CoCa) are toxic when given at maximum tolerated dose to achieve optimal clinical response
Treatment with as low as 10 μM Emodin led to significant decrease in CoCa cell viability at 48 h (DLD-1 21%, p < 0.001; COLO 201 28%, p < 0.01) and 72 h (DLD-1 51%, p < 0.01; COLO 201 52%, p < 0.01)
When compared to the control, at 24 h, a ~ 40% reduction in cell viability (DLD-1 cells, 41%, p < 0.01; COLO 201, 40%, p < 0.001) was observed with 20 μM Emodin treatment of CoCa cells
Summary
Offered therapeutics to treat colon cancer (CoCa) are toxic when given at maximum tolerated dose to achieve optimal clinical response. Less toxic therapeutic intervention is needed to treat CoCa. In this study, we investigated the effect of a natural agent, Emodin, on CoCa. Colorectal cancer is the third most diagnosed and second leading cause of cancer-related deaths in both men and women in the United States [1, 2]. Current treatment options [9] fail to achieve optimal clinical response due to Extensive research to assess the potential of nutrients and herbal extracts as a single agent or as an additive to conventional therapeutics has been conducted in cancer prevention and treatment [10,11,12,13]. Studies have shown that Emodin promotes apoptosis, inhibits DNA synthesis, and promotes free
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