The Probable Target Of Antitumor Thiochromanone Derivatives

Microtubules constitute the major components of the cytoskeleton and play crucial rolesin the cell morphology and mitotic spindle assembly. Especially in the process of cell mitosis,when cells enter the split phase, the tubulin depolymerized by microtubule involved in thespindle assembly. Any drugs with interfering tubulin polymerization and depolymerizationwill prevent the cell cycle, causing apoptosis. Therefore, the microtubule targets has been thehot topics in the study of anticancer drugs.Toll-like receptors (TLRs) is a kind of pattern recognition receptors, TLRs can improveimmune system function, activate NF kappa B signaling pathways, predominate regulatingTNF alpha, interleukins, interferons alpha and a variety of cytokine secretion through avariety of signal transmission. The naturally powerful immunostimulatory property of TLRagonists can be exploited for active immunotherapy against cancer, several TLRs agonistshave been confirmed to have antitumor effect, such as imiquimod and resiquimod.This article will discuss possible antitumor targets of thiochromanones derivativesthrough two ways. One is tubulin, and the other is TLRs.At first, the tubulin was purified from porcine brain, then detect the initial concentrationof tubulin using BCA assay, finally identified it by SDS-PAGE electrophoresis. Secondly,purified tubulin was used for tubulin polymerization-depolymerization assay. The tubulinpolymerization-depolymerization activity was evaluated by the turbidity method andultrastructure observation method. Purified tubulin was tested by using typical tubulininhibitors colchicine and taxol, and confirmed to satisfy experiment requirement. This studyfound that CMMT, CMFT, CMCT, BMFT and CMMOT could inhibit tubulin polymerization.The experiments for investigating whether the chemical have TLRs agonist effects showedthat CMFT possessed LPS-like effect, it can activated mice peritoneal macrophages,improved the secretion of TNFα, IL-6and IL-12. These results sugessted that CMFT may be aTLRs agonist.This study shows that CMMT, CMFT, CMCT, BMFT and CMMOT can inhibit the polymerization of tubulin; CMFT may be a TLRs agonist, it had LPS-like effect, couldsignificantly enhance the level of TNFα, IL-6and IL-12in abdominal macrophages. Theresults showed that the probable targets of Novel Antitumor Thiochromanone Derivativesmay be tubulin and TLRs, further confirm it through different experiment is very importantfor studying the antitumor mechanism of the Thiochromanone Derivatives.