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• W4386226976 endingPage "110681" @default.
• W4386226976 startingPage "110681" @default.
• W4386226976 abstract "Laxiflorin B is a natural ent-kaurane diterpenoid that can be isolated from the leaves of the Isodon eriocalyx var. laxiflora, a perennial shrub native to parts of China. While this compound has potent cytotoxic activity against various tumor cells, the anti-tumor targets and molecular mechanisms of Laxiflorin B are unclear. Here, we show that Laxiflorin B exhibits strong antiproliferative and proapoptotic effects on triple-negative breast cancer (TNBC) cells. At the mechanistic level, we show that β-tubulin (TUBB) is a cellular target of Laxiflorin B. By covalently binding the Cys239 and C354 residues of the TUBB colchicine-binding site, Laxiflorin B disturbs microtubule integrity and structure in vitro and in vivo. Cytotoxicity analyses also showed that the α, β-unsaturated carbonyl in the D ring of Laxiflorin B is responsible for mediating its covalent binding and anti-tumor activity. To assess the therapeutic effects of Laxiflorin B, we synthesized a Laxiflorin B-ALA pro-drug and delivered it by intraperitoneal injection (10 mg/kg) into a 4T1 orthotopic tumor mouse model. Drug treatment had anti-tumor effects without inducing notable weight loss or organ dysfunction. We conclude that Laxiflorin B is a promising colchicine binding site inhibitor that might be exploited in the context of TNBC treatment in the future." @default.
• W4386226976 created "2023-08-29" @default.
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• W4386226976 date "2023-09-01" @default.
• W4386226976 modified "2023-09-26" @default.
• W4386226976 title "Laxiflorin B covalently binds the tubulin colchicine-binding site to inhibit triple negative breast cancer proliferation and induce apoptosis" @default.
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• W4386226976 doi "https://doi.org/10.1016/j.cbi.2023.110681" @default.
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• W4386226976 hasPublicationYear "2023" @default.
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