Trichothecin inhibits invasion and metastasis of colon carcinoma associating with SCD-1-mediated metabolite alteration

Chaoliang Liao, Min Li, Xiang Li, Namei Li, Xu Zhao, Xiaoyi Wang, Yawen Song, Jing Quan, Can Cheng, Jikai Liu, Ann M. Bode, Ya Cao, Xiangjian Luo

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Lipid metabolic abnormalities have received intensified concerns and increased de novo synthesis of lipids is recognized as a common feature of many human cancers. Nevertheless, the role of lipid metabolism that confers aggressive properties on human cancers still remains to be revealed. Natural compounds represent an abundant pool of agents for the discovery of novel lead compounds. Trichothecin (TCN) is a sesquiterpenoid originating from an endophytic fungus of the herbal plant Maytenus hookeri Loes. Here, we assess the association of stearoyl-CoA desaturase 1 (SCD-1) over-expression with malignant progression of colorectal cancer (CRC). Based on this association, the effect of TCN on migration and invasion of colon carcinoma cells closely related to the inhibition of SCD-1 is evaluated. We further demonstrate that reduced production of unsaturated fatty acids (FAs) by blocking SCD-1 activity is beneficial for the anti-invasion effect of TCN. The aim of this study was to clarify the mechanistic connection between metabolite alterations induced by metabolic rewiring and the aggressive tumor phenotype and further develop novel pharmacological tools for the intervention of tumor invasion associated with SCD-1-mediated metabolite alterations.

Original languageEnglish (US)
Article number158540
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1865
Issue number2
DOIs
StatePublished - Feb 2020

Bibliographical note

Funding Information:
This work was supported by grants from the National Natural Science Foundation of China ( 81874195 , 81573014 ), Nanjing Medical Science and technique Development Foundation ( YKK15122 , QRX17187 ), the Innovative Free Orientation Project of Central South University (No. 201810533369 , 201810533406 ).

Funding Information:
This work was supported by grants from the National Natural Science Foundation of China (81874195, 81573014), Nanjing Medical Science and technique Development Foundation (YKK15122, QRX17187), the Innovative Free Orientation Project of Central South University (No. 201810533369, 201810533406). The authors declare no conflict of interest.

Publisher Copyright:
© 2019 The Author(s)

Keywords

  • Colorectal carcinoma
  • Invasion and metastasis
  • Lipid metabolism
  • SCD-1
  • Trichothecin
  • Unsaturated fatty acid

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