title: Cytotoxic effects of loperamide hydrochloride on canine cancer cells.
abstract: Loperamide is a peripheral opiate agonist that can cause apoptosis and G2/M arrest in human cancer cell lines and may sensitize cells to chemotherapy. The objectives of this study were to investigate the effects of loperamide on viability, apoptosis and cell cycle kinetics in canine cancer cells and to establish whether the drug sensitizes cells to doxorubicin. Cell viability was assessed using Alamar Blue. Cell death and cell cycle were studied using flow cytometry with 7-Aminoactinomycin-D (7-AAD) and propidium iodide (PI), respectively. Loperamide decreased cell viability in a dose-dependent fashion and was most effective against canine osteosarcoma cells. In all cell lines, it induced a dose and time dependent apoptosis and resulted in accumulation in G0/G1. When co-incubated with doxorubicin, loperamide induced a synergistic cell kill in canine carcinoma cells. Investigation is warranted into the role of loperamide in the treatment of canine cancer.
authors: University of Georgia, Department of Small Animal Medicine and Surgery, 501 DW Brooks Dr., Athens, GA 30602, U.S.A.
authors: Rebecca Cohen
authors: RC
authors: Regan
authors: Robert Michael
authors: RM
authors: Gogal
authors: James Perry
authors: JP
authors: Barber
authors: Richard Cary
authors: RC
authors: Tuckfield
authors: Elizabeth Wynne
authors: EW
authors: Howerth
authors: Jessica Ann
authors: JA
authors: Lawrence
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D003609:Dactinomycin / Q000031:analogs & derivatives; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D004357:Drug Synergism; D005434:Flow Cytometry; D008139:Loperamide / Q000494:pharmacology*; D010078:Oxazines; D011419:Propidium; D014407:Tumor Cells, Cultured / Q000187:drug effects*; D014966:Xanthenes
chemical_list: D010078:Oxazines; D014966:Xanthenes; D003609:Dactinomycin; C005843:resazurin; D011419:Propidium; D008139:Loperamide; C025942:7-aminoactinomycin D; D004317:Doxorubicin
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