BF12, a novel benzofuran, exhibits anti-tumor activity by inhibiting microtubules and the PI3K/Akt/mTOR signaling pathway in human cervical cancer cells.

BF12 [(E)-3-(6-methoxy-2-(1-(3, 4, 5-trimethoxyphenyl) vinyl) benzo-furan-5-yl) carboxylic acid], a novel derivative of combretastatin-A4 (CA-4), was previously found to inhibit tumor cell lines, with a particularly strong inhibitory effect on cervical cancer cells. In this study, we investigated the microtubule polymerization effects and apoptosis signaling mechanism of BF12. BF12 showed a potent efficiency against cervical cancer cells, SiHa and HeLa, with IC 50 values of 1.10 and 1.06 μM, respectively. The cellular mechanism studies revealed that BF12 induced G2/M phase arrest and apoptosis in SiHa and HeLa cells, which were associated with alterations in the expression of the cell G2/M cycle checkpoint- related proteins (cyclin B1 and cdc2) and alterations in the levels of apoptosis-related proteins (P53, caspase-3, Bcl-2, and Bax) of these cells, respectively. Western blot analysis showed that BF12 inhibited the PI3K/Akt/mTOR signaling pathway and induced apoptosis in human cervical cancer cells. BF12 was identified as a tubulin polymerization inhibitor, evidenced by the effective inhibition of tubulin polymerization and heavily disrupted microtubule networks in living SiHa and HeLa cells. By inhibiting the PI3K/Akt/mTOR signaling pathway and inducing apoptosis in human cervical cancer cells, BF12 shows promise for use as a microtubule inhibitor.