Cucurbitacin E Chemosensitizes Colorectal Cancer Cells via Mitigating TFAP4/Wnt/β-Catenin Signaling

Journal of Agricultural and Food Chemistry
Peng YangZhuoyu Li

Abstract

Chemoresistance and toxicity are the main obstacles that limit the efficacy of 5-fluorouracil (5-FU) in colorectal cancer (CRC) therapy. Hence, it is urgent to identify new adjuvants that can sensitize CRC cells to conventional chemotherapeutic approaches. Cucurbitacin E (CE) is a natural triterpenoid, widely distributed in dietary plants, and shows antitumor effects. Here, we report that CE enhances the sensitivity of CRC cells to chemotherapy via attenuating the expression of adenosine 5'-triphosphate (ATP)-binding cassette transporters ABCC1 and MDR1. Combined with CE-functionalized magnetite nanoparticles and gene ontology analysis, we found that CE-binding proteins may involve Wnt/β-catenin signaling. To validate the findings, β-catenin was upregulated in drug-resistant cell lines, and the synergistic effects of CE and chemotherapeutics were accompanied by the downregulation of β-catenin. Moreover, TFAP4 was identified as an intracellular target of CE. Remarkably, the combination of CE and 5-FU treatment attenuated β-catenin, MDR1, and ABCC1 expressions, while TFAP4 overexpression reversed their expressions by 2.68 ± 0.46-, 0.72 ± 0.44-, and 0.93 ± 0.21-fold, respectively. Thus, our results indicate that CE sensitizes CRC ...Continue Reading

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Citations

Feb 9, 2021·Critical Reviews in Food Science and Nutrition·Li GaoJiaoyan Ren
Apr 8, 2021·Cancer Chemotherapy and Pharmacology·Min LiuZhicheng Gong

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