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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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Related in: MedlinePlus

Loperamide caused an accumulation of cells in the G0/G1 phase as assessed by flowcytometry. Representative flow cytometry histograms of D-17 cells are displayed forcells treated for 48 hr with loperamide (30 µM) (B) and control(A).
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fig_003: Loperamide caused an accumulation of cells in the G0/G1 phase as assessed by flowcytometry. Representative flow cytometry histograms of D-17 cells are displayed forcells treated for 48 hr with loperamide (30 µM) (B) and control(A).

Mentions: Percentage of cells in G0/G1 at three different time points and three differentloperamide concentrations. Values are expressed as mean ± SEM from three independentexperiments. An * indicates that there are significantly more G0/G1 cells compared tothe control (0 µM of drug) as analyzed via ANOVA with Tukey post-hoctest.


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 caused an accumulation of cells in the G0/G1 phase as assessed by flowcytometry. Representative flow cytometry histograms of D-17 cells are displayed forcells treated for 48 hr with loperamide (30 µM) (B) and control(A).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig_003: Loperamide caused an accumulation of cells in the G0/G1 phase as assessed by flowcytometry. Representative flow cytometry histograms of D-17 cells are displayed forcells treated for 48 hr with loperamide (30 µM) (B) and control(A).
Mentions: Percentage of cells in G0/G1 at three different time points and three differentloperamide concentrations. Values are expressed as mean ± SEM from three independentexperiments. An * indicates that there are significantly more G0/G1 cells compared tothe control (0 µM of drug) as analyzed via ANOVA with Tukey post-hoctest.

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