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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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Doxorubicin alone is represented by the interrupted line, while the combination ofdoxorubicin and loperamide is represented by the non-interrupted line. Concentrationsthat exhibit synergism are represented by the *. Loperamide concentration in A-C is 10µM, while it is 25 µM in D. The curves arerepresentative samples of experiments performed in triplicate.
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fig_004: Doxorubicin alone is represented by the interrupted line, while the combination ofdoxorubicin and loperamide is represented by the non-interrupted line. Concentrationsthat exhibit synergism are represented by the *. Loperamide concentration in A-C is 10µM, while it is 25 µM in D. The curves arerepresentative samples of experiments performed in triplicate.

Mentions: Loperamide sensitized canine cancer cells to doxorubicin: Four cell lineswere screened to determine if loperamide increased the sensitivity of cancer cells to thechemotherapeutic drug doxorubicin in vitro. There was no evidence ofsynergism for the D-17, CML-1 or CMT-12 cell lines with 10 µM loperamide.However, there was synergism between the two drugs at 100 nM of doxorubicin and 10µM loperamide for the CTAC cell line. Due to the fact that theIC50 of the CMT-12 cell line was higher than the other three cell lines, theexperiment was repeated using the same concentrations of doxorubicin, but with 25µM of loperamide, nearer to the IC50. This combination showedsignificant synergism at doxorubicin concentrations>10 nM (Fig. 4Fig. 4.


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)

Doxorubicin alone is represented by the interrupted line, while the combination ofdoxorubicin and loperamide is represented by the non-interrupted line. Concentrationsthat exhibit synergism are represented by the *. Loperamide concentration in A-C is 10µM, while it is 25 µM in D. The curves arerepresentative samples of experiments performed in triplicate.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig_004: Doxorubicin alone is represented by the interrupted line, while the combination ofdoxorubicin and loperamide is represented by the non-interrupted line. Concentrationsthat exhibit synergism are represented by the *. Loperamide concentration in A-C is 10µM, while it is 25 µM in D. The curves arerepresentative samples of experiments performed in triplicate.
Mentions: Loperamide sensitized canine cancer cells to doxorubicin: Four cell lineswere screened to determine if loperamide increased the sensitivity of cancer cells to thechemotherapeutic drug doxorubicin in vitro. There was no evidence ofsynergism for the D-17, CML-1 or CMT-12 cell lines with 10 µM loperamide.However, there was synergism between the two drugs at 100 nM of doxorubicin and 10µM loperamide for the CTAC cell line. Due to the fact that theIC50 of the CMT-12 cell line was higher than the other three cell lines, theexperiment was repeated using the same concentrations of doxorubicin, but with 25µM of loperamide, nearer to the IC50. This combination showedsignificant synergism at doxorubicin concentrations>10 nM (Fig. 4Fig. 4.

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