Eugenol potentiates cisplatin anti-cancer activity through inhibition of ALDH-positive breast cancer stem cells and the NF-κB signaling pathway

Molecular Carcinogenesis
Syed S IslamAbdelilah Aboussekhra

Abstract

Triple-negative breast tumors are very aggressive and contain relatively high proportion of cancer stem cells, and are resistant to chemotherapeutic drugs including cisplatin. To overcome these limitations, we combined eugenol, a natural polyphenolic molecule, with cisplatin to normalize cisplatin mediated toxicity and potential drug resistance. Interestingly, the combination treatment provided significantly greater cytotoxic and pro-apoptotic effects as compared to treatment with eugenol or cisplatin alone on several triple-negative breast cancer cells both in vitro and in vivo. Furthermore, adding eugenol to cisplatin potentiated the inhibition of breast cancer stem cells by inhibiting ALDH enzyme activity and ALDH-positive tumor initiating cells. We provide also clear evidence that eugenol potentiates cisplatin inhibition of the NF-κB signaling pathway. Indeed, the binding of NF-κB to its cognate binding sites present in the promoters of IL-6 and IL-8 was dramatically reduced, which led to potent down-regulation of the IL-6 and IL-8 cytokines upon combination treatment relative to the single agents. Similar effects were observed on proliferation, inhibition of epithelial-to-mesenchymal transition and stemness markers in tumo...Continue Reading

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Citations

Mar 18, 2020·International Journal of Molecular Sciences·Maura CalvaniClaudio Favre
Jun 7, 2020·International Journal of Molecular Sciences·Milad AshrafizadehGautam Sethi
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Dec 16, 2020·Drug Development and Industrial Pharmacy·Wen YuanYanling Gong
Mar 23, 2021·Oxidative Medicine and Cellular Longevity·Oana M AburelLaura C Rusu
May 1, 2021·International Journal of Molecular Sciences·Magdalena Ulanowska, Beata Olas
Dec 29, 2021·Journal of Molecular Modeling·Hezha O RasulArif Kivrak

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