LOPERAMIDE IN CANINE CANCER CELLS

30 31 Loperamide is a peripheral opiate agonist that can cause apoptosis and G2/M arrest in human 32 cancer cell lines and may sensitize cells to chemotherapy. The objectives of this study were to 33 investigate the effects of loperamide on viability, apoptosis and cell cycle kinetics in canine 34 cancer cells and to establish whether the drug sensitizes cells to doxorubicin. Cell viability was 35 assessed using Alamar Blue. Cell death and cell cycle were studied using flow cytometry with 36 7-Aminoactinomycin-D (7-AAD) and propidium iodide (PI), respectively. Loperamide 37 decreased cell viability in a dose-dependent fashion and was most effective against canine 38 osteosarcoma cells. In all cell lines, it induced a dose and time dependent apoptosis and resulted 39 in accumulation in G0/G1. When co-incubated with doxorubicin, loperamide induced a 40 synergistic cell kill in canine carcinoma cells. Investigation is warranted into the role of 41 loperamide in the treatment of canine cancer. 42 43

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