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Abstract Title:

β-Sitosterol Reverses Multidrug Resistance via BCRP Suppression by Inhibiting the p53-MDM2 Interaction in Colorectal Cancer.

Abstract Source:

J Agric Food Chem. 2020 Mar 13. Epub 2020 Mar 13. PMID: 32167760

Abstract Author(s):

Ziyuan Wang, Yueping Zhan, Jian Xu, Yang Wang, Mingyu Sun, Jia Chen, Tingyu Liang, Lili Wu, Ke Xu

Article Affiliation:

Ziyuan Wang

Abstract:

Phytosterols are widely present in vegetable oils, nuts, cereal products, fruits, and berries. Phytosterol-induced treatment sensitivity has recently shed light on alleviating multidrug resistance in cancer therapy. Here, we demonstrated thatβ-sitosterol, the most common dietary phytosterol, recovers oxaliplatin (OXA) sensitivity in drug-resistant colorectal cancer (CRC) cells by inhibiting breast cancer resistance protein (BCRP) expression. We further showed evidence that β-sitosterol could activate p53 by disrupting the p53-MDM2 interaction, leading to an increase in p53 translocation to the nucleus and silencing the nuclear factor-κB (NF-κB) pathway, which is necessary for BCRP expression. Finally, we suggested that the combination of OXA and β-sitosterol has a synergistic tumor suppression effect in vivo using a xenograftmouse model. These results revealed that β-sitosterol is able to mediate the p53/NF-κB/BCRP signaling axis to regulate the response of CRC to chemotherapy. The combined application of β-sitosterol and OXA can be a potential way to improve CRC treatment.

Study Type : In Vitro Study

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