Determining the Mechanisms by Which Membrane Targeted Dietary Bioactives Reduce Oncogenic KRas Driven Nutrient Scavenging

Abstract

Approximately 30 to 50% of colorectal cancers contain KRas mutations, which confer resistance to standard therapy and have therefore been termed “undruggable.” Since no curative treatments for KRas driven colon cancer are available, there is a critical need to develop toxicologically innocuous KRas therapeutic approaches that are free of safety problems intrinsic to drugs administered over long periods of time. The present study will investigate the mechanisms underlying previous observations that membrane targeted dietary bioactives (MTDBs) attenuate oncogenic Ras driven nutrient scavenging. The overall goal of the study is to link perturbations in plasma membrane organization and cytoskeletal remodeling to reductions in macropinocytosis and ultimately cell proliferation. For this purpose, we have utilized a human colon adenocarcinoma cell line as an in vitro model. These experiments are relevant to the chemoprevention field, i.e., colorectal cancer prevention

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