title: Loperamide, an FDA-approved antidiarrhea drug, effectively reverses the resistance of multidrug resistant MCF-7/MDR1 human breast cancer cells to doxorubicin-induced cytotoxicity.
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.
authors.affiliation: Department of Oral Pathology, Howard University, Washington, DC, USA. yzhou@howard.edu
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Zhou
authors.forename: Rajagopalan
authors.initials: R
authors.lastname: Sridhar
authors.forename: Liang
authors.initials: L
authors.lastname: Shan
authors.forename: Wei
authors.initials: W
authors.lastname: Sha
authors.forename: Xinbin
authors.initials: X
authors.lastname: Gu
authors.forename: Saraswati
authors.initials: S
authors.lastname: Sukumar
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000235:genetics; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000930:Antidiarrheals / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008139:Loperamide / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020112:Rhodamine 123 / Q000493:pharmacokinetics
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D000930:Antidiarrheals; D012333:RNA, Messenger; D020112:Rhodamine 123; D008139:Loperamide; D004317:Doxorubicin