RT Journal Article SR Electronic T1 P-gp Inhibition by the Anti-psychotic Drug Pimozide Increases Apoptosis, as well as Expression of pRb and pH2AX in Highly Drug-resistant KBV20C Cells JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 5685 OP 5692 DO 10.21873/anticanres.12905 VO 38 IS 10 A1 JI YEONG KIM A1 YUJIN PARK A1 BYUNG-MU LEE A1 HYUNG SIK KIM A1 SUNGPIL YOON YR 2018 UL http://ar.iiarjournals.org/content/38/10/5685.abstract AB Background/Aim: The present study was designed to identify drugs that could sensitize P-glycoprotein (P-gp)-overexpressing resistant KBV20C cancer cells to treatment with Halaven (HAL) or vincristine (VIC). Materials and Methods: Using relatively low doses or IC50 concentrations of drugs to sensitize anti-mitotic drug-resistant KBV20C cells, pimozide (PIM) sensitized HAL-resistant KBV20C cancer cells, with higher P-gp inhibitory activity than another anti-psychotic drug, fluphenazine (FLU). Results: The first-generation P-gp inhibitor verapamil required a dose that was similar to that of PIM for P-gp inhibition, suggesting that PIM has a similar specificity for binding P-gp to prevent efflux of anti-mitotic drugs. Furthermore, co-treatment with PIM and another anti-mitotic drug, VIC, also increased sensitization of KBV20C cells, suggesting that PIM can be combined with other anti-mitotic drugs to sensitize resistant cancer cells. PIM caused a reduction in cell viability and an increase in the number of cells arresting at the G2 phase of the cell cycle. PIM induced both early and late apoptosis in KBV20C cells in response to HAL treatment. Furthermore, the DNA damage marker pH2AX, the cell-cycle protein pRb, and the pro-apoptotic protein C-PARP levels increased after HAL-PIM co-treatment, indicative of a mechanism involving G2 phase arrest and an increase in the number of cells undergoing apoptosis. Conclusion: PIM may be a promising therapeutic agent for the treatment of cancers that are resistant to anti-mitotic drugs.