A new compound Trichomicin exerts antitumor activity through STAT3 signaling inhibition - 30/11/19

Doi : 10.1016/j.biopha.2019.109608

Fengchang Zhu ^a,^b,^{^{1
Both authors contributed equally to this work.}}, Xi Zhao ^a,^{^{1
Both authors contributed equally to this work.}}, Junping Li ^c, Lianhong Guo ^a, Liping Bai ^a,⁎ , Xiaoqiang Qi ^a,^d,⁎
^a NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
^b Chinese Pharmaceutical Association, Beijing, 100050, China
^c Sport Science College of Beijing Sport University, Beijing, 100084, China
^d Department of Surgery and Ellis Fischel Cancer Center, University of Missouri-Columbia, Columbia, MO, 65212, United States

^⁎Corresponding authors at: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Tian Tan Xi Li No.1, Beijing, 100050, China.Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences & Peking Union Medical CollegeTian Tan Xi Li No.1Beijing100050China

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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.

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Abbreviations : STAT3, JAK, IL-6, IL-6R, GAPDH, MTT, FBS, PBS, DMSO, HPLC, ELISA, PCR, LPS, PMA

Keywords : Trichomicin, Nature product, Compound, Antitumor, JAK/STAT3

Plan

Introduction

Material and methods

Fungal material and cultivation

Compound extraction and isolation

Determination of compound structure and physical property

Cell line, cell culture, and reagents

Cytotoxic activities assay

Detection of Rhodamine 123 accumulation by flow cytometry

Preclinical evaluation of acute toxicity

Apoptosis assay by flow cytometry

Fluorescence staining

Western blot analysis

ELISA for Quantification of IL-6

Real time quantitative PCR

Luciferase reporter gene assay

Statistical analysis

Results

Isolation and identification of Trichomicin as a new compound with bioactivity

Identification of Trichomicin’s antitumor activity

Identification of Trichomicin’s capability to reverse drug resistance in cancer cell

Toxicity assay of Trichomicin

Trichomicin-induced cancer cell apoptosis

Trichomicin suppressed IL-6 expression and inhibited STAT3 phosphorylation

Trichomicin blocked IL-6/STAT3 signaling pathway

Discussion

Conclusion

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Vol 121

Article 109608- janvier 2020 Retour au numéro

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A new compound Trichomicin exerts antitumor activity through STAT3 signaling inhibition - 30/11/19

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