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

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

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)20-30
Number of pages11
JournalCancer Letters
Volume448
DOIs
StatePublished - Apr 28 2019

Bibliographical note

Funding Information:
This work was supported by Henan Joint Fund, National Natural Science Foundation China ( NSFC ) [grant number U1804196 and 81572812 ] and Key program of Henan Province, China [grant number 161100510300 ].

Publisher Copyright:
© 2019 Elsevier B.V.

Keywords

  • Colon cancer
  • COX1/2
  • DIM
  • ERK1/2
  • Patient-derived xenograft

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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