Loperamide, an antidiarrhea drug, has antitumor activity by inducing cell apoptosis

Cytotoxic Effects of Loperamide Hydrochloride on Canine Cancer Cells

“…Cell death in the canine cancer cell lines investigated here was mediated in part by apoptosis, as demonstrated through 7-AAD staining and flow cytometry, a technique shown to correlate well with other common apoptosis analyses, such as Annexin-V and propidium iodide [ 15 , 25 ]. The mechanism behind apoptosis in these cell lines has not been elucidated, although in human cancer cell lines, loperamide has been shown to cause apoptosis via activation of the caspase 3 pathway [ 5 ]. Apoptotic canine cancer cells were identified at 24 hr, which was slightly later than with human cancer cells, as apoptosis was evident as early as 6 hr following loperamide exposure [ 5 ].…”

“…The mechanism behind apoptosis in these cell lines has not been elucidated, although in human cancer cell lines, loperamide has been shown to cause apoptosis via activation of the caspase 3 pathway [ 5 ]. Apoptotic canine cancer cells were identified at 24 hr, which was slightly later than with human cancer cells, as apoptosis was evident as early as 6 hr following loperamide exposure [ 5 ]. This may be a reflection of different assays used or possibly decreased potency against canine cells; it is possible that with higher doses of loperamide, a significant change in 7-AAD staining would have been noted prior to 24 hr.…”

“…The exact mechanism of action of cancer cell death in these studies is unknown, but theories include an interaction with somatostatin receptors [ 6 ] or potentially alternative splice variants of the opiate receptor [ 2 ]. Loperamide was recently shown to induce dose-dependent anti-proliferative and apoptotic effect on multiple human cancer cell lines, including breast, bone, lung and liver tumor cell lines [ 5 ]. The 50% inhibitory concentrations (IC 50 values) obtained for most tumor lines tested varied from 23 µ M to 41 µ M, however, an osteosarcoma cell line was most sensitive with an IC 50 of approximately 12 µ M [ 5 ].…”

“…Loperamide was recently shown to induce dose-dependent anti-proliferative and apoptotic effect on multiple human cancer cell lines, including breast, bone, lung and liver tumor cell lines [ 5 ]. The 50% inhibitory concentrations (IC 50 values) obtained for most tumor lines tested varied from 23 µ M to 41 µ M, however, an osteosarcoma cell line was most sensitive with an IC 50 of approximately 12 µ M [ 5 ]. Additionally, loperamide caused a dose-dependent arrest in the G2/M phase of the cell cycle, suggesting that loperamide may function as a radiation sensitizer [ 5 ].…”

“…The 50% inhibitory concentrations (IC 50 values) obtained for most tumor lines tested varied from 23 µ M to 41 µ M, however, an osteosarcoma cell line was most sensitive with an IC 50 of approximately 12 µ M [ 5 ]. Additionally, loperamide caused a dose-dependent arrest in the G2/M phase of the cell cycle, suggesting that loperamide may function as a radiation sensitizer [ 5 ].…”