trans-Trimethoxyresveratrol

Trans-Trimethoxyresveratrol (trans-trismethoxy Resveratrol; (E)-Resveratrol trimethyl ether; trans-3,5,4'-Trimethoxystilbene) is an orally active natural derivative of Resveratrol (HY-16561). Trans-Trimethoxyresveratrol has an enhanced anticancer profile compared to Resveratrol, exhibiting higher potency than resveratrol, with improved cancer cell proliferation inhibition, induction of cell cycle arrest, decreased metastasis, and increased apoptosis. Trans-Trimethoxyresveratrol causes microtubule disassembling and tubulin depolymerization and exerts anti-angiogenic effects through VEGFR2. Trans-Trimethoxyresveratrol can be used for the studies of anti-angiogenic and anti-cancer (such as non-small cell lung cancer and osteosarcoma)^{[1][2][3][4][5][6]}. In Vitro:Trans-Trimethoxyresveratrol exhibits significant cytotoxic potencies against several tumor cells with IC₅₀s of 0.8 g/mL (A549 cells), 1.2 μM (MDA-MB-231 cells) and 2.5 μM (LNCaP cells) ^[1].
. Trans-Trimethoxyresveratrol (1-100 μM, 24-72 h) is 30 to 100 times more potent than Resveratrol in inhibiting endothelial cell proliferation, sprouting, collagen gel invasion, and morphogenesis (ID₅₀ = 0.3-3.0 μM)^[2].
Trans-Trimethoxyresveratrol (1 μM, 3 h) significantly disrupts the microtubule network and inhibits the formation of the lumen^[2].
Trans-Trimethoxyresveratrol (1 μM, 24 h) induces apoptosis only in subconfluent endothelial cells and apoptotic regression of immature vessels in the ex vivo rat aorta ring assay^[2].
Trans-Trimethoxyresveratrol (0.1 μM, 6 h) can quickly (within 30 minutes) cause the blood flow in zebrafish embryos to stop, and the formed blood vessels can be eliminated within 6 hours^[2].
Trans-Trimethoxyresveratrol (300 pmol/implant, 48 h) inhibits blood vessel growth and causes the disappearance of pre-existing blood vessels in the area vasculosa of the chick embryo^[2].
Trans-Trimethoxyresveratrol (3-100 μM, 20 h) downregulates of VEGFR2 and induces G2/M cell-cycle arrest of zebrafish embryos^[3].
Trans-Trimethoxyresveratrol (0.5-50 μM, 48 h) reduces Gefitinib (HY-50895) resistance in H1299 and PC-9/GR cells via suppressing MAPK/Akt/Bcl-2 pathway by upregulation of miR-345 and miR-498^[4].
Trans-Trimethoxyresveratrol (1-10 μM, 0-24 h) can induce the generation of ROS and DNA damage, activate the p53/PUMA/Bax pathway, and enhance the apoptosis sensitivity of 143B cells^[6].
In Vivo:Trans-Trimethoxyresveratrol (30 mg/kg, p,o., once daily for 30 days) exerts anti-tumor effects in H1299 cells induced xenograft mice model^[4].
Trans-Trimethoxyresveratrol (1 mg/kg, p,o., every two days for 4 weeks) significantly inhibited tumor growth in 143B cells induced mice xenograft model^[6].