Abstract Title:

3,3'-Diindolylmethane inhibits patient-derived xenograft colon tumor growth by targeting COX1/2 and ERK1/2.

Abstract Source:

Cancer Lett. 2019 Feb 1 ;448:20-30. Epub 2019 Feb 1. PMID: 30716361

Abstract Author(s):

Xueli Tian, KangDong Liu, Xueyin Zu, Fayang Ma, Zhi Li, MeeHyun Lee, Hanyong Chen, Yan Li, Yuzhou Zhao, Fangfang Liu, Naomi Oi, Ann M Bode, Zigang Dong, Dong Joon Kim

Article Affiliation:

Xueli Tian


3,3'-Diindolymethane (DIM) is a dimeric condensation product of indole-3-carbinol (I3C) that is found in broccoli and cabbage. Although DIM has been reported to exhibit anticancer properties against multiple tumor types, the direct target proteins of DIM have not been fully investigated. In the present study, we report that DIM is a novel COX1/2 and ERK1/2 inhibitor that suppresses growth of colon cancer in vitro and in vivo. To identify possible molecular targets of DIM, 11 potential candidate proteins were validated by an in vitro kinase or enzyme assay. We found that DIM directly inhibits COX1/2 and ERK1/2 protein activities in vitro. Additionally, the PGE2 production (COX-mediated metabolite) and phosphorylated RSK expression (ERK1/2 direct downstream kinase) were strongly suppressed by DIM in colon cancer cells. The inhibition of cell growth by DIM is dependent on the expression of COX1/2 or ERK1/2 proteins. Notably, oral administration of DIM suppressed patient-derived xenograft colon tumor growth in an in vivo mouse model. Overall these results suggest that DIM is a potent and dual COX1/2 and ERK1/2 inhibitor that might be used for chemotherapy against colon cancer.

Study Type : Animal Study, In Vitro Study

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