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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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Morphological changes of the D-17 cell line after treating with 0, 10 and 100µM of loperamide for 24 hr. Cell morphology changed from anattached spindle-shaped appearance (control) to detached and rounded with increasingdoses of loperamide. This is a representative cell line, as all others showed similarchanges.
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fig_002: Morphological changes of the D-17 cell line after treating with 0, 10 and 100µM of loperamide for 24 hr. Cell morphology changed from anattached spindle-shaped appearance (control) to detached and rounded with increasingdoses of loperamide. This is a representative cell line, as all others showed similarchanges.

Mentions: IC50 concentrations for 4 canine cancer cell lines after 24, 48 and 72 hrof incubation with loperamide. There was no difference in IC50 based ontime, as analyzed via ANOVA with Tukey post-hoc test. Values are expressed as mean ±SEM from three independent experiments.


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)

Morphological changes of the D-17 cell line after treating with 0, 10 and 100µM of loperamide for 24 hr. Cell morphology changed from anattached spindle-shaped appearance (control) to detached and rounded with increasingdoses of loperamide. This is a representative cell line, as all others showed similarchanges.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig_002: Morphological changes of the D-17 cell line after treating with 0, 10 and 100µM of loperamide for 24 hr. Cell morphology changed from anattached spindle-shaped appearance (control) to detached and rounded with increasingdoses of loperamide. This is a representative cell line, as all others showed similarchanges.
Mentions: IC50 concentrations for 4 canine cancer cell lines after 24, 48 and 72 hrof incubation with loperamide. There was no difference in IC50 based ontime, as analyzed via ANOVA with Tukey post-hoc test. Values are expressed as mean ±SEM from three independent experiments.

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