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Article

Arctigenin Enhances the Cytotoxic Effect of Doxorubicin in MDA-MB-231 Breast Cancer Cells

Department of Pharmacology, School of Medicine and Intractable Disease Research Center, Dongguk University, Gyeongju 38066, Korea
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Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(8), 2997; https://doi.org/10.3390/ijms21082997
Received: 7 April 2020 / Revised: 21 April 2020 / Accepted: 21 April 2020 / Published: 23 April 2020
(This article belongs to the Special Issue Bioactive Phytochemicals for Cancer Prevention and Treatment II)
Several reports have described the anti-cancer activity of arctigenin, a lignan extracted from Arctium lappa L. Here, we investigated the effect of arctigenin (ATG) on doxorubicin (DOX)-induced cell death using MDA-MB-231 human breast cancer cells. The results showed that DOX-induced cell death was enhanced by ATG/DOX co-treatment in a concentration-dependent manner and that this was associated with increased DOX uptake and the suppression of multidrug resistance-associated protein 1 (MRP1) gene expression in MDA-MB-231 cells. ATG enhanced DOX-induced DNA damage and decreased the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and the expressions of RAD51 and survivin. Cell death caused by ATG/DOX co-treatment was mediated by the nuclear translocation of apoptosis inducing factor (AIF), reductions in cellular and mitochondrial Bcl-2 and Bcl-xL, and increases in mitochondrial BAX levels. However, caspase-3 and -7 did not participate in DOX/ATG-induced cell death. We also found that DOX/ATG-induced cell death was linked with activation of the p38 signaling pathway and suppressions of the phosphorylations and expressions of Akt and c-Jun N-terminal kinase. Taken together, these results show that ATG enhances the cytotoxic activity of DOX in MDA-MB-231 human breast cancer cells by inducing prolonged p21 expression and p38-mediated AIF-dependent cell death. In conclusion, our findings suggest that ATG might alleviate the side effects and improve the therapeutic efficacy of DOX. View Full-Text
Keywords: arctigenin; doxorubicin; triple-negative breast cancer; apoptosis-inducing factor; cell death arctigenin; doxorubicin; triple-negative breast cancer; apoptosis-inducing factor; cell death
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MDPI and ACS Style

Lee, K.-S.; Lee, M.-G.; Kwon, Y.-S.; Nam, K.-S. Arctigenin Enhances the Cytotoxic Effect of Doxorubicin in MDA-MB-231 Breast Cancer Cells. Int. J. Mol. Sci. 2020, 21, 2997. https://doi.org/10.3390/ijms21082997

AMA Style

Lee K-S, Lee M-G, Kwon Y-S, Nam K-S. Arctigenin Enhances the Cytotoxic Effect of Doxorubicin in MDA-MB-231 Breast Cancer Cells. International Journal of Molecular Sciences. 2020; 21(8):2997. https://doi.org/10.3390/ijms21082997

Chicago/Turabian Style

Lee, Kyu-Shik, Min-Gu Lee, Yun-Suk Kwon, and Kyung-Soo Nam. 2020. "Arctigenin Enhances the Cytotoxic Effect of Doxorubicin in MDA-MB-231 Breast Cancer Cells" International Journal of Molecular Sciences 21, no. 8: 2997. https://doi.org/10.3390/ijms21082997

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