ABSTRACT
BACKGROUND/OBJECTIVES@#Colorectal cancer (CRC) is the third most common cancer worldwide and has a high recurrence rate, which is associated with cancer stem cells (CSCs).β-carotene (BC) possesses antioxidant activity and several anticancer mechanisms. However, no investigation has examined its effect on colon cancer stemness.MATERIALS/METHODS: CD133 + CD44 + HCT116 and CD133+ CD44+ HT-29 cells were isolated and analyzed their self-renewal capacity by clonogenic and sphere formation assays.Expressions of several CSCs markers and Wnt/β-catenin signaling were examined. In addition, CD133+ CD44+ HCT116 cells were subcutaneously injected in xenograft mice and analyzed the effect of BC on tumor formation, tumor volume, and CSCs markers in tumors. @*RESULTS@#BC inhibited self-renewal capacity and CSC markers, including CD44, CD133, ALDH1A1, NOTCH1, Sox2, and β-catenin in vitro. The effects of BC on CSC markers were confirmed in primary cells isolated from human CRC tumors. BC supplementation decreased the number and size of tumors and delayed the tumor-onset time in xenograft mice injected with CD133+ CD44+ HCT116 cells. The inhibitory effect of BC on CSC markers and the Wnt/β-catenin signaling pathway in tumors was confirmed in vivo as well. @*CONCLUSIONS@#These results suggest that BC may be a potential therapeutic agent for colon cancer by targeting colon CSCs.
ABSTRACT
BACKGROUND/OBJECTIVES@#Bitter taste receptors are taste signaling pathway mediators, and are also expressed and function in extra-gustatory organs. Skin aging affects the quality of life and may lead to medical issues. The purpose of this study was to better understand the anti-skin aging effects of bitter taste receptors in D-galactose (D-gal)-induced aged human keratinocytes, HaCaT cells.MATERIALS/METHODS: Expressions of bitter taste receptors in HaCaT cells and mouse skin tissues were examined by polymerase chain reaction assay. Bitter taste receptor was overexpressed in HaCaT cells, and D-gal was treated to induce aging. We examined the effects of bitter taste receptors on aging by using β-galactosidase assay, wound healing assay, and Western blot assay. @*RESULTS@#TAS2R16 and TAS2R10 were expressed in HaCaT cells and were upregulated by D-gal treatment. TAS2R16 exerted protective effects against skin aging by regulating p53 and p21, antioxidant enzymes, the SIRT1/mechanistic target of rapamycin pathway, cell migration, and epithelial-mesenchymal transition markers. TAS2R10 was further examined to confirm a role of TAS2R16 in cellular senescence and wound healing in D-gal-induced aged HaCaT cells. @*CONCLUSIONS@#Our results suggest a novel potential preventive role of these receptors on skin aging by regulating cellular senescence and wound healing in human keratinocyte, HaCaT.