Jia Cheng Qian,Dan Liu,Li Ping Lin,Wen Jing Zhu,Ren Xiang Tan
Kimchi is a globally consumed food with diverse health-benefits, but the low-abundance bioactive compounds in kimchi remain largely neglected. Here we show that kimchi contains a family of low-abundance (0.5–1.6 μg/g, dried weight) high-order indole oligomers derived from indole-3-carbinol (I3C), a breakdown product released from cruciferous vegetables used for producing the traditional subsidiary food. The structure determination of such complex molecules was accomplished by synthesizing linear indole oligomers as standard materials followed by the LC–HR–MS analysis. One indole tetramer (LTe2) is substantially toxic to tumor MV4-11 (IC 50 = 1.94 μM) and THP-1 cells (IC 50 = 7.12 μM). Collectively, the work adds valuable information to the knowledge package about kimchi, and may inspire the generation of indole-based molecules, to which many drugs belong.
Wen Jing Zhu,Li Ping Lin,Dan Liu,Jia Cheng Qian,Bei Bei Zhou,Dan Dan Yuan,Ren Xiang Tan
Globally consumed kimchi is manufactured through fermenting cruciferous vegetables containing indole glucosinolates (IG). But few reports describe the IG metabolism during the fermentation. Here, we show that indole-3-carbinol (I3C), a breakdown product of IG, is transformed during the kimchi fermentation into 3,3′-diindolylmethane (DIM) and 2-(indol-3-ylmethyl)-3,3′-diindolylmethane (LTr1). LTr1 was found to kill the acute myeloid leukemia (AML) cells with FMS-like tyrosine kinase 3 (FLT3) receptor mutations, by inhibiting the FLT3 phosphorylation and the expression of downstream proteins (STAT5, ERK, and AKT). In the immune-depleted mice xenografted with human MV4-11 cells, LTr1 was demonstrated to reduce the tumor growth and synergize with sorafenib, an anti-AML agent in clinic. The work updates the chemical and biological knowledge about kimchi, and in particular establishes LTr1 as an FLT3 inhibitor that is effective and synergistic with sorafenib in treating AML.