BF12, a Novel Benzofuran, Exhibits Antitumor Activity by Inhibiting Microtubules and the PI3K/Akt/mTOR Signaling Pathway in Human Cervical Cancer Cells
Yiting Gao
Department of Medicinal and Organic Chemistry, School of Pharmacy, Xinjiang Medical University, Beijing Road 393#, Xinshi District, Urumqi, 830011 P. R. China
Search for more papers by this authorCorresponding Author
Cheng Ma
Department of Medicinal and Organic Chemistry, School of Pharmacy, Xinjiang Medical University, Beijing Road 393#, Xinshi District, Urumqi, 830011 P. R. China
Search for more papers by this authorXuezhao Feng
Department of Medicinal and Organic Chemistry, School of Pharmacy, Xinjiang Medical University, Beijing Road 393#, Xinshi District, Urumqi, 830011 P. R. China
Search for more papers by this authorYang Liu
Department of Medicinal and Organic Chemistry, School of Pharmacy, Xinjiang Medical University, Beijing Road 393#, Xinshi District, Urumqi, 830011 P. R. China
Search for more papers by this authorXiaohelaiti Haimiti
Department of Medicinal and Organic Chemistry, School of Pharmacy, Xinjiang Medical University, Beijing Road 393#, Xinshi District, Urumqi, 830011 P. R. China
Search for more papers by this authorYiting Gao
Department of Medicinal and Organic Chemistry, School of Pharmacy, Xinjiang Medical University, Beijing Road 393#, Xinshi District, Urumqi, 830011 P. R. China
Search for more papers by this authorCorresponding Author
Cheng Ma
Department of Medicinal and Organic Chemistry, School of Pharmacy, Xinjiang Medical University, Beijing Road 393#, Xinshi District, Urumqi, 830011 P. R. China
Search for more papers by this authorXuezhao Feng
Department of Medicinal and Organic Chemistry, School of Pharmacy, Xinjiang Medical University, Beijing Road 393#, Xinshi District, Urumqi, 830011 P. R. China
Search for more papers by this authorYang Liu
Department of Medicinal and Organic Chemistry, School of Pharmacy, Xinjiang Medical University, Beijing Road 393#, Xinshi District, Urumqi, 830011 P. R. China
Search for more papers by this authorXiaohelaiti Haimiti
Department of Medicinal and Organic Chemistry, School of Pharmacy, Xinjiang Medical University, Beijing Road 393#, Xinshi District, Urumqi, 830011 P. R. China
Search for more papers by this authorAbstract
BF12 [(2E)-3-[6-Methoxy-2-(3,4,5-trimethoxybenzoyl)-1-benzofuran-5-yl]prop-2-enoic acid], a novel derivative of combretastatin A-4 (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 IC50 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 PI3 K/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 PI3 K/Akt/mTOR signaling pathway and inducing apoptosis in human cervical cancer cells, BF12 shows promise for use as a microtubule inhibitor.
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