title: Curcumin Induces Apoptosis of Colorectal Cancer Stem Cells by Coupling with CD44 Marker.
abstract: This study investigated the effect of curcumin on colorectal cancer stem cells (CCSCs) and its possible mechanism. 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 indeed increase apoptosis of CRC cells as well as of CCSCs, but at a significant level only in CD44(+) cells. 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 our 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.
authors.affiliation: Institute of Food Science and Technology, College of Bio-resources and Agriculture, National Taiwan University , Taipei 10617, Taiwan.
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Huang
authors.affiliation: Institute of Food Science and Technology, College of Bio-resources and Agriculture, National Taiwan University , Taipei 10617, Taiwan.
authors.forename: Yu-Wei
authors.initials: YW
authors.lastname: Lin
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University , Taipei 10051, Taiwan.
authors.forename: Han-Mo
authors.initials: HM
authors.lastname: Chiu
authors.affiliation: Institute of Food Science and Technology, College of Bio-resources and Agriculture, National Taiwan University , Taipei 10617, Taiwan.
authors.forename: Been-Huang
authors.initials: BH
authors.lastname: Chiang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000473:pathology*; D003474:Curcumin / Q000378:metabolism / Q000494:pharmacology*; D005973:Glutamine / Q000032:analysis; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis* / Q000378:metabolism; D055442:Metabolome; D014411:Neoplastic Stem Cells / Q000737:chemistry / Q000187:drug effects*
chemical_list: D018960:Hyaluronan Receptors; D005973:Glutamine; D003474:Curcumin
keywords: CD44; apoptosis; cancer stem cells; colorectal cancer; colorectal cancer stem cells; curcumin