scutellarein and Colonic-Neoplasms

Scutellarein has been identified to serve an anti‑tumor function in human colon cancer, but the underlying mechanisms remain largely unclear. The present study further investigated the effect and mechanism of scutellarein, extracted from wild chrysanthemum, in the progression of colon cancer. MTT, clone formation, flow cytometry and tumor‑bearing mice assays were used to detect cell viability, clone formation, apoptosis and tumorigenesis, respectively. Western blot and quantitative PCR assays were performed for protein and mRNA expression detection. The results revealed that, compared with the control group, scutellarein treatment significantly inhibited the viability and induced the apoptosis of colon cancer cells (P<0.05), with significant decreases in receptor for advanced glycosylation end products (RAGE) protein expression and stability and an increase in RAGE ubiquitination (P<0.05). However, the effects of scutellarein exerted in cell apoptosis and viability were rescued by RAGE overexpression, and accelerated by RAGE knockdown. Additionally, it was observed that scutellarein treatment induced a significant increase in the expression of cell division control protein 4 (CDC4) compared with the control group (P<0.05), which was then verified to interact with RAGE protein and mediate its ubiquitination. Overexpression of CDC4 inhibited colon cancer cell viability and promoted the apoptosis of SW480 and T84 cells, whereas this function was weakened when RAGE was overexpressed. Furthermore, CDC4 downregulation significantly neutralized scutellarein functions in promoting cell apoptosis and inhibiting cell viability and tumorigenesis in colon cancer cells compared with the scutellarein group (P<0.05). In conclusion, the present study revealed that scutellarein inhibited the development of colon cancer through upregulating CDC4‑mediated RAGE ubiquitination.

Topics: Animals; Apigenin; Cell Line, Tumor; Colonic Neoplasms; F-Box-WD Repeat-Containing Protein 7; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Proteins; Receptor for Advanced Glycation End Products; Ubiquitination; Xenograft Model Antitumor Assays

To search novel therapy for human colon cancer, scutellarein identified from

Topics: Apigenin; Apoptosis; Colonic Neoplasms; Cytochromes c; HCT116 Cells; Humans; Mitochondria; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species; Scutellaria

To investigate the absorption and transepithelial transport characteristics of scutellarin and scutellarein in the human colonic adenocarcinoma cell (Caco-2) monolayer model. The influence factors on these two compounds' absorption were investigated, such as buffer solution, duration of culture, and inhibitors of multidrug resistance-associated protein 2 (MRP(2)), breast cancer drug resistance protein (BCRP) and P-glycoprotein (P-gp).. By using Caco-2 monolayer as an intestinal epithelial cell model, the transport process was studied from apical (AP) side to basolateral (BL) side or from BL to AP. The two compounds were determined by high-performance liquid chromatography coupled with diode-array-detector detection. Transport parameters and apparent permeability coeffients (P(app)) were calculated.. The P(app) values of scutellarin and scutellarein were different in two buffer solutions, respectively. In phosphate buffered saline, scutellarin had no absorption from AP to BL, while its P(app) value was 0.74×10(-6) to 1.58×10(-6) cm/s from BL to AP. The P(app) values of scutellarein were 4.33×10(-6) to 6.79×10(-6) cm/s and 1.32×10(-6) to 2.56×10(-6) cm/s from AP to BL and from BL to AP, respectively. The P(app) value gradually decreased with time. The absorption of scutellarein was better than that of scutellarin. The scutellarin absorption was improved by verapamil, MK-571 and reserpine. The scutellarein absorption was improved by verapamil whereas its excretion was improved by MK-571.. Absorption of scutellarin is difficult in Caco-2 monolayer cells, which contributes to its low bioavailability. Scutellarein absorption is better than scutellarin absorption. Scutellarein transepithelial transport is passive diffusion. The inhibitor of P-gp can improve scutellarin and scutellarein transportation. The inhibitors of MRP(2) and BCRP can promote transportation of scutellarin. The inhibitor of MRP(2) can promote efflux of scutellarein. The multidrug resistance-associated protein may be the second reason for low bioavailability of scutellarin.

Topics: Adenocarcinoma; Apigenin; Biological Transport; Caco-2 Cells; Colonic Neoplasms; Glucuronates; Humans; Multidrug Resistance-Associated Protein 2