In vitro effect of 5-fluorouracil and paclitaxel on Echinococcus granulosus larvae and cells

Abstract

Human cystic echinococcosis is a zoonosis caused by the metacestode stage of the tapeworm Echinococcus granulosus. Although benzimidazole compounds such as albendazole and mebendazole have been the cornerstone of chemotherapy for the disease, there is often no complete recovery after treatment. Hence, in searching for novel treatment options, we examined the in vitro efficacies of 5-fluorouracil (5-FU) and paclitaxel (PTX) against E. granulosus germinal cells, protoscoleces and cysts. 5-FU or PTX inhibited the growth of E. granulosus cells in a time dependent manner. Although both treatments had a protoscolicidal effect, 5-FU had a considerably stronger effect than PTX. 5-FU produced a dose- and time-dependent effect, provoking the complete loss of viability after 24 days of incubation. Moreover, cysts did not develop following the inoculation of treated protoscoleces into mice. The loss of viability was slower in PTX treated protoscoleces, reaching to approximately 60% after 30 days. The results of the in vitro treatment with 5-FU and PTX were similar in secondary murine cysts. The employment of SEM and TEM allowed us to examine, at an ultrastructural level, the effects induced by 5-FU and PTX on E. granulosus germinal cells, protoscoleces and murine cysts. In conclusion, the data obtained clearly demonstrated that 5-FU and PTX at clinically achievable concentrations inhibit the survival of larval cells, protoscoleces and metacestodes. In vivo studies to test the antiparasitic activities of 5-FU and PTX are currently being undertaken on the murine model of cystic echinococcosis.

Diterpenes as lead molecules against neglected tropical diseases

“…When infecting humans, Echinococcus granulosus, Echinococcus multilocularis, Echinococcus oligarthrus, and Echinococcus vogeli are localized in the liver (in 75% of cases), the lungs (in 5-15% of cases), and other organs such as the spleen, brain, heart, and kidneys (in 10-20% of cases). Paclitaxel with 5fluorouracil at dose 1-10 μg/mL effectively inhibited the growth of E. granulosus (Pensel et al, 2014). It was suggested that paclitaxel may act by arresting both interphase and mitotic cell cycle phases in E. granulosus.…”

Efficacy of ursolic acid against Echinococcus granulosus in vitro and in a murine infection model

“…The proteasome inhibitor, bortezomib, which was developed for myeloma chemotherapy, displays high activity against E. multilocularis metacestodes in vitro although the activity of this drug was lower than that of albendazole and induced adverse effects in vivo [ 5 ]. Furthermore, 5-fluorouracil and paclitaxel [ 6 ], as well as imatinib [ 7 ], exhibit profound anti-parasitic activity against E. multilocularis . These results suggest that novel candidate drugs for the treatment of CE might be found among the chemicals with antitumor effects.…”

Molecular Characteristics and Serodiagnostic Potential of Dihydrofolate Reductase from Echinococcus granulosus

“…The PSCs were separated in sterile conditions and washed three times in phosphate-buffered saline (PBS). Rinsed PSCs were diluted to a concentration of 1,500 mL −1 and maintained as previously described 33, 47 . Briefly, PSCs were cultured in RPMI 1640 medium (Hyclone) with 10% fetal bovine serum (Hyclone), 10% hydatid fluid, 100 U.mL −1 penicillin G and 100 μg.mL −1 streptomycin (Sigma, USA).…”