Anticancer Activity of Tubulosine through Suppression of Interleukin-6-Induced Janus Kinase 2/Signal Transducer and Activation of Transcription 3 Signaling
- Author:
Byung Hak KIM
1
;
Eun Hee YI
;
Yu Chen LI
;
In Chul PARK
;
Jung Youl PARK
;
Sang Kyu YE
Author Information
- Publication Type:Original Article
- Keywords: Breast neoplasms; IL-6; Janus Kinase 2; STAT3 Transcription Factor; Tubulosine
- MeSH: Blotting, Western; Breast Neoplasms; Cell Death; Cell Line; DNA Nucleotidylexotransferase; Drosophila; Fluorescent Antibody Technique; Glycoproteins; Humans; Immunoprecipitation; In Vitro Techniques; Interleukin-6; Interleukins; Janus Kinase 2; Phosphorylation; Phosphotransferases; Polymerase Chain Reaction; Receptors, Interleukin-6; Reverse Transcription; STAT3 Transcription Factor; Transducers; Tyrosine
- From:Journal of Breast Cancer 2019;22(3):362-374
- CountryRepublic of Korea
- Language:English
- Abstract: PURPOSE: The chemical structure of tubulosine has been known since the mid-1960s. However, little is known about its biological and pharmacological functions. The aim of this study was to investigate the novel functions of tubulosine in cancer treatment, specifically in breast cancer. METHODS: An Unpaired (Upd)-induced Drosophila cell line and interleukin (IL)-6-stimulated human breast cancer cell lines were used to investigate the biological and pharmacological activities of tubulosine in vitro. To investigate the activities of tubulosine, we performed molecular and cellular experiments such as Western blot and reverse transcription polymerase chain reaction analyses, immunoprecipitation and terminal deoxynucleotidyl transferase dUTP nick end labeling assays, and immunofluorescence staining using breast cancer cell lines. RESULTS: Tubulosine exhibited anticancer activity in IL-6-stimulated human breast cancer cells. Moreover, tubulosine reduced the tyrosine phosphorylation level and transcriptional activity of signal transducer and activator of transcription (STAT) protein at 92E in Upd-induced Drosophila cells. Additionally, tubulosine suppressed IL-6-induced Janus kinase 2 (JAK2)/STAT3 signaling, resulting in decreased viability and induction of apoptotic cell death in breast cancer cells. Interestingly, inhibition of IL-6-induced JAK2/STAT3 signaling by tubulosine was associated with the blocking of IL-6 receptor (IL-6R) and glycoprotein 130 (gp130) binding. CONCLUSION: Tubulosine exhibits anticancer activity through functional inhibition of IL-6-induced JAK2/STAT3 signaling by targeting IL-6Rα/gp130 binding in breast cancer cells. These findings suggest that tubulosine may hold promise for the treatment of inflammation-associated cancers, including breast cancer.
