Sasa quelpaertensis Leaf Extract Inhibits Colon Cancer by Regulating Cancer Cell Stemness in Vitro and in Vivo.
A rare subpopulation of cancer cells, termed cancer stem cells (CSCs), may be responsible for tumor relapse and resistance to conventional chemotherapy. The development of a non-toxic, natural treatment for the elimination of CSCs is considered a strategy for cancer treatment with minimal side effects. In the present study, the potential for Sasa quelpaertensis leaf extract (SQE) and its two bioactive compounds, tricin and p-coumaric acid, to exert anti-CSC effects by suppressing cancer stemness characteristics were evaluated in colon cancer cells. CD133+CD44+ cells were isolated from HT29 and HCT116 cell lines using flow-activated cell sorting (FACs). SQE treatment was found to significantly suppress the self-renewal capacity of both cell lines. SQE treatment was also associated with the down-regulation of β-catenin and phosphorylated GSK3β, while significantly enhancing cell differentiation by up-regulating CK20 expression and blocking the expression of several stem cell markers, including DLK1, Notch1, and Sox-2. In vivo, SQE supplementation suppressed tumor growth in a xenograft model by down-regulating stem cell markers and β-catenin as well as HIF-1α signaling. Compared with two bioactive compounds of SQE, SQE exhibited the most effective anti-CSC properties. Taken together, these results provide evidence that SQE inhibits colon cancer by regulating the characteristics of CSCs.
Department of Nutritional Science and Food Management, Ewha Womans University, Seoul 120-750, Korea. 009267@naver.com.
Soo Jin
SJ
Min
Department of Nutritional Science and Food Management, Ewha Womans University, Seoul 120-750, Korea. godlovesme86@hanmail.net.
Ji Ye
JY
Lim
National Academy of Agricultural Science, Rural Development Administration, Jeollabuk-do 565-851, Korea. kimhrr@korea.kr.
Haeng Ran
HR
Kim
Department of Biology, Jeju National University, Jejusi, Jeju 690-756, Korea. jejusasa@naver.com.
Se-Jae
SJ
Kim
Department of Nutritional Science and Food Management, Ewha Womans University, Seoul 120-750, Korea. yuri.kim@ewha.ac.kr.
Yuri
Y
Kim
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002135:Calcium-Binding Proteins; D003110:Colonic Neoplasms / Q000188:drug therapy*; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D018515:Plant Leaves / Q000737:chemistry; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D031787:Sasa / Q000737:chemistry*; D051176:beta Catenin / Q000378:metabolism
D000071916:AC133 Antigen; D015703:Antigens, CD; D000970:Antineoplastic Agents; D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C000606023:PROM1 protein, human; D010455:Peptides; D010936:Plant Extracts; C000606024:Prom1 protein, mouse; D051881:Receptor, Notch1; D055748:SOXB1 Transcription Factors; D051176:beta Catenin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3