The limitation of the model is that the anti-cryptosporidial leads/hits need to be MDR1 substrates.

This model can be employed for studying the action of additional anti-cryptosporidial leads, and adapted to studying drug action in other epicellular pathogens.

Conclusions Data confirmed that, at efficacious concentrations, paclitaxel acted mainly on the parasite target, while doxorubicin might act on both parasite and host cell targets. Increased drug tolerance in host cells had no effect on antiparasitic efficacy of paclitaxel, but affected that of doxorubicin HCl. Transient overexpression of MDR1 increased drug tolerance of HCT-8 cells on paclitaxel, doxorubicin HCl and vincristine sulphate (2.11- to 2.27-fold increase), but not on cyclosporin A, daunorubicin HCl and nitazoxanide. Results Six known anti-cryptosporidial leads were tested. The approach was based on the theory that, for an epicellular parasite receiving consistent exposure to compounds in culture medium, overexpressing MDR1 in HCT-8 cells would increase drug tolerance of host cells to selected compounds but would not affect the anti-cryptosporidial efficacy if the compounds acted solely on the parasite target and the drug action on host cell target played no role on the antiparasitic efficacy. In vitro cytotoxicity and anti-cryptosporidial efficacy of selected compounds were evaluated on the parasite grown in WT parental and transiently transfected HCT-8 cells. Methods Transient overexpression of a multidrug resistance protein 1 (MDR1) gene in host cells (HCT-8 cell line) was explored to increase drug tolerance of the host cells to selected anti-cryptosporidial leads. on-target or off-target effect) against the zoonotic enteric parasite Cryptosporidium parvum. Yang, Bo Wang, Dongqiang Liu, Mingxiao Wu, Xiaodong Yin, Jigang Zhu, GuanДЄbstract Objectives To rapidly generate host cells with resistance to multiple compounds for differentiating drug action on parasite target or the host cell target (i.e. Host cells with transient overexpression of MDR1 as a novel in vitro model for evaluating on-target effect for activity against the epicellular Cryptosporidium parasite Host cells with transient overexpression of MDR1 as a novel in vitro model for evaluating.

Acad 2016 use in acad 2005