Abstract
BACKGROUND/PURPOSE: Explorations of novel regimens enhancing efficacy and selectivity of chemotherapeutic agents are urgent to solve the problems of cancer therapy. This study aimed to explore synergistic anticancer effects of novel regimens of phytopolyphenols [curcumin (C), tea polyphenols (G) or GC] with celecoxib (Cl) and ZnSO(4). MATERIALS AND METHODS: Antiproliferative effects of drugs on cultured cancer cells and pathogenic biofilms were assayed by MTT and optical density (OD600) respectively; their inhibition on efflux pump (Na(+)-K(+)-ATPase) was measured by colorimetric methods. Synergistic (CI < 1) anticancer effects were evaluated by the equations of combination index (CI) and efficacy index (EI). RESULTS: Both Cl and methotrexate (MTX) alone exhibited inhibitory effects not only on proliferation and efflux pump of cultured cancer cells but also pathogenic biofilm formation. Phytopolyphenols (P) and MTX potentiated these inhibitory effects of Cl. In addition, novel regimens containing Cl, memantine (Mem) or thioridazine (TRZ) further enhanced not only efficacy and selectivity of anticancer effects but also inhibition on efflux pump and pathogenic biofilm formation of four chemotherapeutic agents (MTX, cisplatin, 5-fluorouracil and doxorubicin) respectively. CONCLUSION: In this study, novel regimens of phytopolyphenols (P), targeting drugs (T; Cl, Mem or TRZ) and metal ions (M; ZnSO(4)) so called PTM regimens exerted not only by themselves but also markedly potentiated efficacy and selectivity of anticancer effects of four chemotherapeutic agents. Because of their potent inhibitions on efflux pump and pathogenic biofilm formation, these combinatorial novel regimens were expected to be able to overcome the problems of multidrug resistant cancers and merit for further clinical studies.