Loperamide, an FDA-Approved Antidiarrhea Drug, Effectively Reverses the Resistance of Multidrug Resistant MCF-7/MDR1 Human Breast Cancer Cells to Doxorubicin-Induced Cytotoxicity

Yanfei ZhouDepartments of Oral Pathology, Radiation Oncology, Radiology, Howard University, Washington, DC, USA, Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USACorrespondence[email protected]

Rajagopalan SridharDepartments of Oral Pathology, Radiation Oncology, Radiology, Howard University, Washington, DC, USA, Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

Liang ShanDepartments of Oral Pathology, Radiation Oncology, Radiology, Howard University, Washington, DC, USA, Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

Wei ShaDepartments of Oral Pathology, Radiation Oncology, Radiology, Howard University, Washington, DC, USA, Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

Xinbin GuDepartments of Oral Pathology, Radiation Oncology, Radiology, Howard University, Washington, DC, USA, Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

Saraswati SukumarDepartments of Oral Pathology, Radiation Oncology, Radiology, Howard University, Washington, DC, USA, Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

Abstract

Loperamide is an FDA-approved antidiarrhea drug which acts on the μ-opioid receptors in the mesenteric plexus of large intestine and exhibits limited side effects. We hypothesized that loperamide might reverse the multidrug resistance (MDR) of human cancer cells to chemotherapeutic agents. MCF-7/MDR1 cells express high level of MDR1 and are resistant to doxorubicin. We found that loperamide significantly enhanced the cytotoxicity of doxorubicin to MCF-7/MDR1 cells in a dose-dependent manner. In conclusion, loperamide reversed the resistance of MCF-7/MDR1 cells to doxorubicin, suggesting that chemotherapy in combination with loperamide may benefit patients with MDR tumors once applied in clinic.

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ACKNOWLEDGMENTS

This work was supported in part by grants Howard/Hopkins Partnership grant, U54 CA091431 (YZ and SS) and P20 CA118770 (Y.Z) from the National Institutes of Health, and DAMD17-03-1-0759 from U.S. Army Medical Research and Materiel Command.

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Loperamide, an FDA-Approved Antidiarrhea Drug, Effectively Reverses the Resistance of Multidrug Resistant MCF-7/MDR1 Human Breast Cancer Cells to Doxorubicin-Induced Cytotoxicity

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Loperamide, an FDA-Approved Antidiarrhea Drug, Effectively Reverses the Resistance of Multidrug Resistant MCF-7/MDR1 Human Breast Cancer Cells to Doxorubicin-Induced Cytotoxicity

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