Evaluation of Sanazole Cytotoxicity in Human Drug-Sensitive and MDR Uterine Sarcoma Cells

Abstract

Chemotherapy is one of the principle modes of cancer treatment. However, cells adapt to repeated chemotherapeutic exposures in several ways resulting in multidrug resistance (MDR). Therefore, it is mandatory to search for effective alternatives that are refractory to resistant mechanisms. In this study, we investigated the cytotoxicity of sanazole, a nitrotriazole derivative known for its hypoxic radio-sensitization, against a human MDR cell line highly expressing P-glycoprotein that functions as an efflux pump to lipophilic drugs. The results showed that MDR cells exhibited initial sensitivity to the drug compared to the parent sensitive cells. Sanazole action was independent of the degree of resistance and P-glycoprotein expression. Prolonged exposures (48 h) to the drug affected both cell phenotypes viability to a similar extent. However, cell cycle analysis revealed that the underlying pathways differed between cells with respect to their p53 status. For instance, cell cycle was halted in G1- and S-phase in parent and MDR cells, respectively. The (apoptotic) DNA fragmentation in MDR cells was dose-dependently higher compared to the parent cells. Sanazole treatment decreased polyploidy in a dose-dependent manner in MDR cells. The present study provides evidence on the possible potential of sanazole multidrug resistant cancer cells.