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Article

Metformin Derivative HL156A Reverses Multidrug Resistance by Inhibiting HOXC6/ERK1/2 Signaling in Multidrug-Resistant Human Cancer Cells

Department of Pathology, School of Dentistry, Chosun University, Gwangju 61452, Korea
*
Author to whom correspondence should be addressed.
They are equally contributed in this paper.
Pharmaceuticals 2020, 13(9), 218; https://doi.org/10.3390/ph13090218
Received: 22 July 2020 / Revised: 24 August 2020 / Accepted: 27 August 2020 / Published: 28 August 2020
(This article belongs to the Special Issue Metformin: Mechanism and Application 2022)
Multidrug resistance is a significant clinical crisis in cancer treatment and has been linked to the cellular expression of multidrug efflux transporters. The aim of this study was to examine the effects and mechanisms of the metformin derivative HL156A on human multidrug resistance (MDR) cancer cells. Here, HL156A significantly suppressed cell growth and colony formation through G2/M phase cell cycle arrest in MDR cancer cells. HL156A also reduced the wound closure rate and cell migration and induced caspase-3-dependent apoptosis. We found that HL156A inhibited the expression of MDR1 by inhibiting the HOXC6-mediated ERK1/2 signaling pathway and increased the sensitivity to paclitaxel or doxorubicin in MDR cells. Furthermore, HL156A significantly inhibited angiogenesis in a chicken chorioallantoic membrane (CAM) assay. These results suggest the potential of the metformin derivative HL156A as a candidate therapeutic modality for the treatment of human multidrug-resistant cancers. View Full-Text
Keywords: metformin; HL156A; multidrug resistance; HOXC6; angiogenesis metformin; HL156A; multidrug resistance; HOXC6; angiogenesis
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MDPI and ACS Style

Jeong, Y.S.; Lam, T.G.; Jeong, S.; Ahn, S.-G. Metformin Derivative HL156A Reverses Multidrug Resistance by Inhibiting HOXC6/ERK1/2 Signaling in Multidrug-Resistant Human Cancer Cells. Pharmaceuticals 2020, 13, 218. https://doi.org/10.3390/ph13090218

AMA Style

Jeong YS, Lam TG, Jeong S, Ahn S-G. Metformin Derivative HL156A Reverses Multidrug Resistance by Inhibiting HOXC6/ERK1/2 Signaling in Multidrug-Resistant Human Cancer Cells. Pharmaceuticals. 2020; 13(9):218. https://doi.org/10.3390/ph13090218

Chicago/Turabian Style

Jeong, Yun Soo, Thuy Giang Lam, Seho Jeong, and Sang-Gun Ahn. 2020. "Metformin Derivative HL156A Reverses Multidrug Resistance by Inhibiting HOXC6/ERK1/2 Signaling in Multidrug-Resistant Human Cancer Cells" Pharmaceuticals 13, no. 9: 218. https://doi.org/10.3390/ph13090218

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