Volume 17, Issue 3 e1900622
Full Paper

BF12, a Novel Benzofuran, Exhibits Antitumor Activity by Inhibiting Microtubules and the PI3K/Akt/mTOR Signaling Pathway in Human Cervical Cancer Cells

Yiting Gao

Yiting Gao

Department of Medicinal and Organic Chemistry, School of Pharmacy, Xinjiang Medical University, Beijing Road 393#, Xinshi District, Urumqi, 830011 P. R. China

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Cheng Ma

Corresponding 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

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Xuezhao Feng

Xuezhao Feng

Department of Medicinal and Organic Chemistry, School of Pharmacy, Xinjiang Medical University, Beijing Road 393#, Xinshi District, Urumqi, 830011 P. R. China

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Yang Liu

Yang Liu

Department of Medicinal and Organic Chemistry, School of Pharmacy, Xinjiang Medical University, Beijing Road 393#, Xinshi District, Urumqi, 830011 P. R. China

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Xiaohelaiti Haimiti

Xiaohelaiti Haimiti

Department of Medicinal and Organic Chemistry, School of Pharmacy, Xinjiang Medical University, Beijing Road 393#, Xinshi District, Urumqi, 830011 P. R. China

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First published: 17 January 2020
Citations: 14

Abstract

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.

Graphical Abstract

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