Brusatol Enhances the Chemotherapy Efficacy of Gemcitabine in Pancreatic Cancer via the Nrf2 Signalling Pathway

Oxidative Medicine and Cellular Longevity
Yukai XiangMengtao Zhou

Abstract

Although gemcitabine is the standard chemotherapy treatment for advanced pancreatic cancer, its benefits are quite limited due to prevalent chemoresistance, and the mechanism underlying gemcitabine chemoresistance remains unclear. Currently, Nrf2 has been deemed as a significant contributor to gemcitabine chemoresistance in pancreatic cancer. Brusatol is a unique inhibitor of the Nrf2 pathway, and in previous studies, we determined that brusatol exhibits the effects of growth inhibition and proapoptosis in pancreatic cancer cells. Due to these data, we speculate that brusatol can reverse gemcitabine-induced Nrf2 activation and propose that it can enhance gemcitabine efficacy in treating pancreatic cancer. In this study, we first proved that brusatol can effectively inhibit the Nrf2 signalling pathway and increase ROS accumulation in pancreatic cancer cells. Next, we demonstrated that brusatol can abrogate gemcitabine-induced Nrf2 activation in pancreatic cancer cells. In addition, we discovered that brusatol potentiates gemcitabine-induced growth inhibition and apoptosis in human pancreatic cancer cells. In nude mice with PANC-1 xenografts, treatment with a combination of brusatol and gemcitabine considerably reduced in vivo tu...Continue Reading

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Citations

Apr 26, 2019·Human & Experimental Toxicology·L A Méndez-GarcíaE J Córdova
Jan 18, 2020·Future Medicinal Chemistry·Hongzhi LinHaopeng Sun
Feb 29, 2020·Antioxidants·Emiliano PanieriLuciano Saso
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Sep 13, 2019·Cell Communication and Signaling : CCS·Jiang-Jiang QinWei-Dong Zhang
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May 18, 2019·Oxidative Medicine and Cellular Longevity·Emiliano Panieri, Luciano Saso
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Jun 12, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Cong ChengShan Cao
Jul 6, 2021·Oxidative Medicine and Cellular Longevity·Zerui WuZhipeng Su
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Jul 11, 2021·Cellular Oncology (Dordrecht)·Michelle van der MerweAnna-Mart Engelbrecht
Dec 9, 2020·Journal of Medicinal Chemistry·Yulin Ren, A Douglas Kinghorn

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Methods Mentioned

BETA
xenografts
xenograft
PCR
protein assay
Assay
ELISA
flow cytometry

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