Background Recent studies have shown that multidrug resistance may be induced by the high stemness of cancer cells. Following prolonged chemotherapy, MDR protein 1 (MDR1) and CD133 increase in CRC, but the relationship between them is unclear. Methods The relationship between MDR and CSC properties in CRC was determined via CCK-8 assay, apoptosis assay, DOX uptake and retention, immunohistochemistry, immunofluorescence and flow cytometry. The correlations between their expression levels were evaluated using Spearman’s rank statistical test and the Mann-Whitney test. Furthermore, the effect of CD133 on the repression of the AKT/NF-κB/MDR1 signalling pathway was investigated in vitro and in vivo. Results We found that CD133 increased with the emergence of drug-resistance phenotypes, and the high expression of MDR1/P-gp was consistently accompanied by positive expression of CD133 as demonstrated by the analysis of patient samples. Up- or downregulation of CD133 could regulate MDR via AKT/NF-κB/MDR1 signalling in CRC. A rescue experiment showed that the AKT/NF-κB signalling pathway is the main mechanism by which CD133 regulates MDR1/P-gp expression in CRC. Conclusions Taken together, our results suggest that targeting CD133 reverses drug resistance via the AKT/NF-κB/MDR1 pathway and that this pathway might serve as a potential therapeutic target to reverse MDR in CRC.

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractRecent studies have shown that MDR could be induced by the high stemness of cancer cells. In a previous study, we found bufalin could reverse MDR and inhibit cancer cell stemness in colorectal cancer, but the relationship between them was unclear.Here we identified overexpressing CD133 increases levels of Akt/nuclear factor-κB signaling mediators and MDR1, while increasing cell chemoresistance. Furthermore, bufalin reverses colorectal cancer MDR by regulating cancer cell stemness through the CD133/nuclear factor-κB/MDR1 pathway in vitro and in vivo. Taken together, our results suggest that bufalin could be developed as a novel 2-pronged drug that targets CD133 and MDR1 to eradicate MDR cells and could ultimately be combined with conventional chemotherapeutic agents to improve treatment outcomes for patients with colorectal cancer. K E Y W O R D Sbufalin, CD133, colorectal cancer, MDR1, multidrug resistance

No abstract

No abstract

Annona squamosa Linn. (custard apple) has been used extensively in India traditional medicine for treatment of dysentery, cardiac problems, fainting, worm infections, constipation, hemorrhage, dysuria, fever. This study assessed the phytochemicals present in the leaves of A. squamosa. The phytochemical was extracted separately with distilled water and 96% ethanol. A wide variety of pharmacologically active compounds such as alkaloids, coumarins, tannins, cardiac glycosides, flavonoids, carbohydrates, phenols, and saponins were found to present in the leaves of A. squamosa. However, terpenoids and phlobatannins were absent in this plant. This study also assessed the contents of phenolics and flavonoids for their in vitro antioxidant activity. The total polyphenol content of ethanol extract of A. squamosa measured by Folin-Ciocalteau reagent in terms of gallic acid equivalent achieved 242.88±6.13 mg GAE/g. The flavonoid content of the plant sample as quercetin equivalent achieved 82,61±0.82 mg QE/g. The antioxidant activity of the ethanol extract of A. squamosa was correlated with total phenolic and flavonoid content with values IC50 of 132.96±1.33 μg/ml, 64.74±0.52 μg/ml for DPPH and ABTS scavenging activity, respectively.