Isorhamnetin

Isorhamnetin is a flavonoid compound extracted from the Chinese herb Hippophae rhamnoides L.. Isorhamnetin suppresses skin cancer through direct inhibition of MEK1 and PI3K. IC50 & Target: MEK1^[1]
PI3K^[1] In Vitro: Isorhamnetin is a plant flavonoid that occurs in fruits and medicinal herbs. Isorhamnetin binds directly to MEK1 in an ATP-noncompetitive manner and to PI3-K in an ATP-competitive manner. In vitro and ex vivo kinase assay data show that Isorhamnetin inhibits the kinase activity of MAP/ERK kinase (MEK) 1 and PI3-K and the inhibition is due to direct binding with Isorhamnetin^[1]. Isorhamnetin inhibits the Akt/mTOR and MEK/ERK signaling pathways, and promotes the activity of the mitochondrial apoptosis signaling pathway. The inhibitory effects of Isorhamnetin on breast cancer cells are determined using the CCK-8 method. Isorhamnetin inhibits the proliferation of numerous breast cancer cells (IC₅₀, ~10 µM), including MCF7, T47D, BT474, BT-549, MDA-MB-231 and MDA-MB-468, whereas less inhibitory activity is observed in the MCF10A normal breast epithelial cell line (IC₅₀, 38 µM)^[2]. In Vivo: Photographic data shows that Isorhamnetin treatment suppresses tumor development in mice. The average volume of tumors in untreated mice increases over time and reaches a volume of 623 mm³ at 4 weeks post-inoculation; however, at this time, in mice treated with 1 or 5 mg/kg Isorhamnetin, the average tumor volume is only 280 or 198 mm³, respectively. At the end of the study, Isorhamnetin treatment (1 or 5 mg/kg) reduces tumor weight compared with the untreated control group^[1].