Butyrate suppresses motility of colorectal cancer cells via deactivating Akt/ERK signaling in histone deacetylase dependent manner.

Butyrate is a typical short chain fatty acid produced by gut microbiota of which the dysmetabolism has been consistently associated with colorectal diseases. However, whether butyrate affects metastatic colorectal cancer is not clear. In this study we investigated in vitro the effect of butyrate on motility, a significant metastatic factor of colorectal cancer cells and explored the potential mechanism. By using wound healing and transwell-based invasion models, we demonstrated that pretreatment of butyrate significantly inhibited motility of HCT116, HT29, LOVO and HCT8 cells, this activity was further attributed to deactivation of Akt1 and ERK1/2. Suberanilohydroxamic acid (SAHA), another HDAC inhibitor, mimicked the inhibitory effect of butyrate on cell motility and deactivation of Akt/ERK. Furthermore, by silencing of HDAC3 with siRNA, we confirmed dependence of butyrate's effect on HDAC3, the similar reduced cell motility observed under HDAC3 silencing also indicates the significance of HDAC itself in cell motility. In conclusion, we confirmed the HDAC3-relied activity of butyrate on inhibiting motility of colorectal cancer cells via deactivating Akt/ERK signaling. Our data indicate that modulating butyrate metabolism is an effective therapeutic strategy of metastatic colorectal cancer; and HDAC3 might be a novel target for management of colorectal cancer metastasis.

• Publication year

  2017

• Venue

  Journal of Pharmacological Sciences

• Publication date

  2017-12-01

• Fields of study

  Biology, Medicine, Environmental Science

• Identifiers
  DOI 10.1016/j.jphs.2017.11.004PMID 29233468
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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