Effect of microenvironment and phytochemicals on the development of colorectal cancer stem cells
Date Issued
2016
Date
2016
Author(s)
Huang, Yu-Ting
Abstract
Colorectal cancer (CRC) is the three major cause of cancer-related mortality in Taiwan. The risk factors of CRC include age, life style and family history. This study investigated the effect of microenvironment and phytochemicals on the development of colorectal cancer stem cells (CCSCs) and its possible mechanism. We analyzed CRC patient’s normal, adenomatous polyps and tumor tissue for expression of CCSCs (CD133 and CD44) and metabolic profiles. We also tried to establish CRC primary cells for investigating the effect of phytochemicals and microenvironmental factors on the CCSCs and metabolic profiles. In addition, the microenviroments factors including reactive oxygen species (ROS)、epidermal growth factor (EGF)及transforming growth factor (TGF) were used to induce the expression of CCSCs. However, both of the attempt of establishing CRC primary culture and induction of CCSCs by microenvironmental factors failed, we decided to use CRC cell lines (HCT-116, HT-29, SW480 and SW620) model to analyze their expression of CCSCs and metabolic profiles. Comparison of the metabolic profiles of human adenomatous polyp (N=61) and colorectal cancer (CRC) (N=57) tissue found statistically significant differences (p<0.05) in their composition of Adenosine monophosphate (AMP), adenine, 5’-methythioadenosine, 3-hydroxybutyric acid, prostaglandin E2, threonine and glutamine. Our cell culture model study found that curcumin treatment (50 μM for 48 h) did increased apoptosis of CRC cells and CCSCs, but only the CD44+ cells reached statistically significant. Further metabolic profile studies of the CRC, CD44+ and CD44- cells indicated that curcumin treatment increased glyceraldehyde and hydroxypropionic acid in CD44- cells, but decreased glutamine content in both curcumin-treated CRC and CD44+ cells. Based on the comparison of the metabolic profiles of human tissues and cancer cells we suggest that curcumin might couple with CD44 and that curcumin-CD44+ coupling at the cell membrane might have some blocking effect on the transport of glutamine into the cells, thus decreasing the glutamine content in the CD44+ cells and inducing apoptosis.
Subjects
colorectal cancer
cancer stem cell
SDGs
Type
thesis
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