Anti malarial Drugs Primaquine and Chloroquine Have Different Sensitization Effects with Anti mitotic Drugs in Resistant Cancer Cells.
The purpose of this study was to identify conditions that would increase the sensitivity of drug resistant cancer cells. Previously, two anti malarial drugs, chloroquine (CHL) and primaquine (PRI) showed different sensitization effects for vinblastine (VIB) resistant cancer cells. Herein, we tested co treatment of cells with CHL or PRI and other microtubule targeting cancer drugs, namely, vinorelbine (VIO) paclitaxel (PAC) docetaxel (DOC) vincristine (VIC) or halaven (HAL) We found that PRI sensitized P glycoprotein (P gp) overexpressing drug resistant KBV20C cells to all six anti mitotic drugs to a similar extent. CHL had a similar sensitization effect only for co treatment with PAC, DOC, VIC, and HAL, while the sensitization effect was less marked for co treatment with VIB or VIO. FACS analysis and western blot analysis revealed that G2arrest and apoptosis showed only a slight increase on co treatment with VIB or VIO and CHL. We also found that phospho histone H3 and pRb were markedly increased only by PRI VIB co treatment, but not by CHL VIB co treatment. This suggests that reduction in the expression of these proteins correlates with decreased G2arrest in CHL VIB co treatment. We further compared the effect of another anti malarial drug, mefloquine (MEF) in combination with the six anti mitotic drugs. We found that MEF and PRI had similar sensitization effects in co treatment with these anti mitotic drugs. PRI and MEF had generally similar sensitization effects in co treatment with anti mitotic drugs, suggesting that they do not have any preferred anti mitotic drug partner in co treatment. This indicates that only CHL shows specificity in co treatment with anti mitotic drugs in resistant cancer cells. Our results may contribute to the choice of anti mitotic drugs to be used in co treatment of resistant cancer cells with the anti malarial drugs, CHL, PRI, and MEF.
Anticancer research