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Cytotoxic effects of loperamide hydrochloride on canine cancer cells.

Regan RC, Gogal RM, Barber JP, Tuckfield RC, Howerth EW, Lawrence JA - J. Vet. Med. Sci. (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: University of Georgia, Department of Small Animal Medicine and Surgery, 501 DW Brooks Dr., Athens, GA 30602, U.S.A.

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.

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Loperamide impaired cell viability following 72 hr of incubation in a dose dependentfashion in CTAC, D-17, CML-1 and CMT-12 canine cancer cell lines. Viability data weregarnered from experiments performed in triplicate and assessed by Alamar Blue assay.Cell viability for both CTAC and CMT-12 was significantly lower than control cells atconcentrations ≥32 µM; cell viability for D-17 and CML-1 wassignificantly lower than control cells at concentrations ≥10 µM.
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fig_001: Loperamide impaired cell viability following 72 hr of incubation in a dose dependentfashion in CTAC, D-17, CML-1 and CMT-12 canine cancer cell lines. Viability data weregarnered from experiments performed in triplicate and assessed by Alamar Blue assay.Cell viability for both CTAC and CMT-12 was significantly lower than control cells atconcentrations ≥32 µM; cell viability for D-17 and CML-1 wassignificantly lower than control cells at concentrations ≥10 µM.

Mentions: Loperamide induced a dose-dependent cytotoxicity in canine cancer celllines: Loperamide produced anti-proliferative effects with increasingconcentrations in all cell lines tested (Fig.1Fig. 1.


Cytotoxic effects of loperamide hydrochloride on canine cancer cells.

Regan RC, Gogal RM, Barber JP, Tuckfield RC, Howerth EW, Lawrence JA - J. Vet. Med. Sci. (2014)

Loperamide impaired cell viability following 72 hr of incubation in a dose dependentfashion in CTAC, D-17, CML-1 and CMT-12 canine cancer cell lines. Viability data weregarnered from experiments performed in triplicate and assessed by Alamar Blue assay.Cell viability for both CTAC and CMT-12 was significantly lower than control cells atconcentrations ≥32 µM; cell viability for D-17 and CML-1 wassignificantly lower than control cells at concentrations ≥10 µM.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4300369&req=5

fig_001: Loperamide impaired cell viability following 72 hr of incubation in a dose dependentfashion in CTAC, D-17, CML-1 and CMT-12 canine cancer cell lines. Viability data weregarnered from experiments performed in triplicate and assessed by Alamar Blue assay.Cell viability for both CTAC and CMT-12 was significantly lower than control cells atconcentrations ≥32 µM; cell viability for D-17 and CML-1 wassignificantly lower than control cells at concentrations ≥10 µM.
Mentions: Loperamide induced a dose-dependent cytotoxicity in canine cancer celllines: Loperamide produced anti-proliferative effects with increasingconcentrations in all cell lines tested (Fig.1Fig. 1.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: University of Georgia, Department of Small Animal Medicine and Surgery, 501 DW Brooks Dr., Athens, GA 30602, U.S.A.

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.

Show MeSH
Related in: MedlinePlus