Dual inhibition of key proliferation signaling pathways in triple negative breast cancer cells by a novel derivative of Taiwanin A

The treatment of breast cancer cells obtained by blocking the aberrant activation of the proliferation signaling pathways PI-3K/Akt/mTOR and MEK/ERK has received considerable attention in recent years. Previous studies showed that Taiwanin A inhibited the proliferation of several types of cancer cells. In this study, we report that 3,4-bis-3,4,5- trimethoxybenzylidene-dihydrofuran (BTMB), a novel derivative of Taiwanin A, significantly inhibited the proliferation of triple negative breast cancer (TNBC) cells both in vitro and in vivo. The results show that BTMB inhibited the proliferation of human TNBC cells by the induction of cell cycle arrest and apoptosis in a dose-dependent fashion. BTMB inhibited the expression of β-catenin, cdc2 and the cell cycle regulatory proteins, cyclin A, cyclin D1 and cyclin E. The mechanism of action was associated with the suppression of cell survival signaling through inactivation of the Akt and ERK 1/2 signaling pathways. Moreover, BTMB induced cell apoptosis through an increase in the expression of BAX, cleaved-caspase-3 and cleaved-poly ADP-ribose polymerase (PARP). Moreover, BTMB inhibited TNBC cell colony formation and sensitized TNBC cells to cisplatin, a chemotherapeutic drug. In a TNBC mouse-xenograft model, BTMB significantly inhibited the growth of mammary carcinomas through decreased expression of cyclin D1. BTMB was shown to significantly suppress the growth of mammary carcinoma and therefore to have potential as an anti-cancer therapeutic agent.

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