The Antitumor Effects And Molecular Mechanism Of 3-bromopropioylnamino Benzoylurea (JIMB01), A Novel Tubulin Ligand

3-Bromopropionylamino benzoylurea (JIMB01) is a small molecular weight compound (MW 313) synthesized in our laboratory. This compound showed antiproliferative activities in a panel of fourteen human tumor cell lines with IC₅₀ values in the range of 0.25 to 0.51 μM for leukemia and lymphoma celllines and 0.33 to 9.26 μM for solid tumor cell lines. The primary action of JIMB01 is to inhibit microtubule polymerization but not depolymerization. JIMB01 at 4 μM caused a complete inhibition of microtubule assembly; JIMB01 at the concentration as high as 32 uM did not inhibit the process of depolymerization. Cell cycle analysis showed that JIMB01 arrested the human hepatocarcinoma BEL-7402 cells at G2/M phase 24 hr after treatment, followed by a programmed cell death. JIMB01-induced apoptosis in cancer cells was confirmed by DNA gel electrophoresis, as well as morphological methods. DNA degradation in the form of a multiple-unit DNA ladder was clearly demonstrated in hepatocarcinoma BEL-7402 cells treated with JIMB01 at 0.8 μM or higher for 48hr, and in CEM...