Potent inhibition of tumor survival in vivo by beta-lapachone plus taxol: combining drugs imposes different artificial checkpoints.

摘要: Ablation of tumor colonies was seen in a wide spectrum human carcinoma cells culture after treatment with the combination β-lapachone and taxol, two low molecular mass compounds. They synergistically induced death cultured ovarian, breast, prostate, melanoma, lung, colon, pancreatic cancer cells. This synergism is schedule dependent; namely, taxol must be added either simultaneously or β-lapachone. therapy has unusually potent antitumor activity against ovarian prostate prexenografted mice. There little host toxicity. Cells can commit to apoptosis at cell-cycle checkpoints, mechanism that eliminates defective ensure integrity genome. We hypothesize when are treated drugs activating more than one different checkpoint, production conflicting regulatory signaling molecules induces β-Lapachone causes delays late G1 S phase, arrests G2/M. both were delayed multiple checkpoints before committing apoptosis. Our findings suggest an avenue for developing anticancer by exploiting apoptosis-prone “collisions” checkpoints.