A new compound Trichomicin exerts antitumor activity through STAT3 signaling inhibition

Fengchang Zhu; Xi Zhao; Junping Li; Lianhong Guo; Liping Bai; Xiaoqiang Qi

doi:10.1016/j.biopha.2019.109608

A new compound Trichomicin exerts antitumor activity through STAT3 signaling inhibition

Biomed Pharmacother. 2020 Jan;121:109608. doi: 10.1016/j.biopha.2019.109608. Epub 2019 Nov 7.

Authors

Fengchang Zhu¹, Xi Zhao², Junping Li³, Lianhong Guo², Liping Bai⁴, Xiaoqiang Qi⁵

Affiliations

¹ NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China; Chinese Pharmaceutical Association, Beijing, 100050, China.
² NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China.
³ Sport Science College of Beijing Sport University, Beijing, 100084, China.
⁴ NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China. Electronic address: lipingbai1973@163.com.
⁵ NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China; Department of Surgery and Ellis Fischel Cancer Center, University of Missouri-Columbia, Columbia, MO, 65212, United States. Electronic address: qixi@health.missouri.edu.

PMID: 31707338
DOI: 10.1016/j.biopha.2019.109608

Abstract

Trichomicin, a novel small-molecule compound isolated from the fungus Trichoderma harzianum and identified as new structure compound, exhibited antitumor activities in various human cancer cell lines and reversed drug resistance activity in the multidrug-resistant cancer cell line KBV. The underlying cellular and molecular mechanism was illuminated. Trichomicin can significantly induce cancer cell apoptosis and reduced IL-6 expression and phosphorylation of STAT3 were found in response to Trichomicin treatment. The blockade of IL-6 mediated JAK-STAT3 signaling pathway by Trichomicin was confirmed using reporter gene system. As a promising antitumor-activity compound, Trichomicin is presented in this study.

Keywords: Antitumor; Compound; JAK/STAT3; Nature product; Trichomicin.

MeSH terms

Animals
Antineoplastic Agents / isolation & purification*
Antineoplastic Agents / pharmacology
Antineoplastic Agents / toxicity
Apoptosis / drug effects
Cell Line, Tumor
Drug Resistance, Neoplasm
Humans
Hypocreales / chemistry*
Interleukin-6 / antagonists & inhibitors
Mice
Phosphorylation
STAT3 Transcription Factor / antagonists & inhibitors*
STAT3 Transcription Factor / physiology
Signal Transduction / drug effects

Substances

Antineoplastic Agents
Interleukin-6
STAT3 Transcription Factor

Supplementary concepts

Trichoderma harzianum