Sasa quelpaertensis Leaf Extract Inhibits Colon Cancer by Regulating Cancer Cell Stemness in Vitro and in Vivo

Abstract

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.

Sasa quelpaertensis leaf extract regulates microbial dysbiosis by modulating the composition and diversity of the microbiota in dextran sulfate sodium-induced colitis mice

“…SQE has shown beneficial effects on colitis in previous studies. Moreover, the bioactive component of SQE, tricin and p -coumaric acid, have exhibited antioxidant, anti-inflammatory, and anticancer effects which remain to be investigated in relation to gut microbiota [17, 18, 20, 34]. …”

“…Its leaf extract has been reported to mediate various health promoting properties, including anti-inflammation, anti-cancer effects, and anti-obesity effect [16–18]. Sasa quelpaertensis leaves extract (SQE) is a mixture of polysaccharides, amino acids, and polyphenols, including p -coumaric acid and tricin, and has exhibited anti-inflammatory and anti-obesity effects [19, 20].…”

p‐Coumaric acid and its conjugates: dietary sources, pharmacokinetic properties and biological activities

“…In vitro studies have indicated that p ‐CA moderately inhibits the growth of some tumour cell lines. p ‐CA significantly decreases the viability of neuroblastoma N2a cells (EC 50 = 104 µmol L −1 ), human lung A549, colon HT29‐D4, and cancer stem cells . However, it inhibits Caco‐2 and ECV304 cells only at high concentrations of up to 1.5 mmol L −1 and 5 mmol L −1 , respectively .…”

The Use of Nutraceuticals to Counteract Atherosclerosis: The Role of the Notch Pathway

“…Withaferin-A (WA), a bioactive compound derived from Withania somnifera, inhibits Notch-1 signaling and cell proliferation in three colon cancer cell lines [286]. Two bioactive compounds (tricin and p-coumaric acid) present in leaf extract of Sasa quelpaertensis Nakai (Poaceae) are able to inhibit the growth of CSCs deriving from different colon cancer cell lines through Dll-1 and Notch-1 inhibition and downregulation of biomarkers related to tumor vascularization (VEGF and HIF-1α) [287]. Curcumin inhibits the activation of Notch-1 and the expression of Jagged-1 as well as HES1 in esophageal cancer cell lines [288].…”