IPP51, a chalcone acting as a microtubule inhibitor with in vivo antitumor activity against bladder carcinoma

摘要: We previously identified 1-(2,4-dimethoxyphenyl)-3-(1-methylindolyl) propenone (IPP51), a new chalcone derivative that is capable of inducing prometaphase arrest and subsequent apoptosis bladder cancer cells. Here, we demonstrate IPP51 selectively inhibits proliferation tumor-derived cells versus normal non-tumor interfered with spindle formation mitotic chromosome alignment. Accumulation cyclin B1 checkpoint proteins Bub1 BubR1 on chromosomes in treated indicated the activation spindle-assembly checkpoint, which consistent arrest. The antimitotic actions other chalcones are often associated microtubule disruption. Indeed, inhibited tubulin polymerization an vitro assay purified tubulin. In cells, induced increase soluble Furthermore, capillary-like tube by endothelial indicating it has anti-angiogenic activity. Molecular docking showed indol group can be accommodated colchicine binding site This characteristic was confirmed competition demonstrating compete for to Finally, human xenograft mouse model, tumor growth without signs toxicity. Altogether, these findings suggest attractive microtubule-targeting agent potential chemotherapeutic value.