The Effect of Phytochemicals on a Chemoresistant, Epithelial‐Mesenchymal Transitioned, Colorectal Cancer Cell Line

Abstract

In 2012, colorectal cancer was the second most common cancer diagnosed in women and the third most common in men. In 2015, an estimated 132,700 new individuals will be diagnosed and 49,700 people will die from the disease. Colorectal cancer, though one of the most common cancers worldwide, is not distributed evenly among the world's population. It is concentrated mainly in countries with a Western culture, specifically the Western diet, such as the United States and Western Europe. A considerably smaller rate of incidence of disease is found in Africa and parts of Asia. This difference in colorectal cancer distribution may be attributed to the increased presence of certain phytochemicals in non‐Western diets. Our hypothesis is that phytochemicals inhibit proliferation of both metastatic and non‐metastatic cancer cell lines. Studies have shown that transdifferentiation into epithelial‐mesenchymal transition (EMT) by chemotherapy leads to the formation of resistant cells. EMT is a process in which epithelial cells acquire a mesenchymal phenotype, characterized by increased migratory and invasive properties. We developed a chemoresistance‐induced epithelial to mesenchymal transitioned colon cancer cell line (DLD‐1 OxR) by exposing the parental cell line (DLD‐1) to increasing concentrations of oxaliplatin (a drug used in the treatment of metastatic colon cancer). The DLD‐1 OxR cell line has undergone EMT and lost its epithelial properties to become a more motile mesenchymal cell type. We used a wound healing assay and transwell assay to assess the migration and invasion of the EMT‐chemoresistant cell line respectively. DLD‐1 and DLD‐1 OxR cells were exposed to curcumin and kaempferol. Curcumin is a phytochemical derived from turmeric, which has been shown to suppress inflammation and inhibit cell proliferation. Kaempferol, a phytochemical found in plants such as broccoli, kale, beans, and leeks, has also shown anti‐inflammatory and anti‐cancerous activity. Both phytochemicals inhibited proliferation of DLD‐1 and DLD‐1 OxR cell lines.Support or Funding InformationKM, KS, and AM are supported by the DeNardo Education and Research Foundation Fellowship.