Luteolin-mediated inhibition of hepatic stellate cell activation via suppression of the STAT3 pathway

Claire B. Cummins, Xiaofu Wang, Omar Nunez Lopez, Gabriel Graham, Hong Yan Tie, Jia Zhou, Ravi Radhakrishnan

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Hepatic stellate cell (HSC) activation is responsible for hepatic fibrogenesis and is associated with an overexpression of transcription 3 (STAT3). Luteolin, a common dietary flavonoid with potent anti-inflammatory properties, has previously demonstrated antifibrogenic properties in HSCs but the mechanism has not been fully elucidated. Activated human and rat hepatic stellate cell lines LX-2 and HSC-T6 were used to study the effects of luteolin on HSCs. Cellular proteins were determined by western blot and immunofluorescence. Cell proliferation was assessed with Alamar Blue assay. Luteolin significantly decreased LX-2 and HSC-T6 cell viability in a time-and-dose-dependent manner, as well as decreased HSC end-products α-smooth muscle actin (α-SMA), collagen I, and fibronectin. Luteolin decreased levels of total and phosphorylated STAT3, suppressed STAT3 nuclear translocation and transcriptional activity, and attenuated expression of STAT3-regulated proteins c-myc and cyclin D1. STAT3 specific inhibitors stattic and SH-4-54 demonstrated similar effects on HSC viability and α-SMA production. In LX-2 and HSC-T6 cells, luteolin demonstrates a potent ability to inhibit hepatic fibrogenesis via suppression of the STAT3 pathway. These results further elucidate the mechanism of luteolin as well as the effect of the STAT3 pathway on HSC activation.

Original languageEnglish (US)
Article number1567
JournalInternational Journal of Molecular Sciences
Volume19
Issue number6
DOIs
StatePublished - Jun 1 2018

Fingerprint

Luteolin
Hepatic Stellate Cells
Chemical activation
retarding
activation
cells
viability
Cell Survival
proteins
smooth muscle
spectral mixture analysis
Proto-Oncogene Proteins c-myc
Proteins
STAT3 Transcription Factor
Flavonoids
collagens
Liver
Cyclin D1
cultured cells
Cell proliferation

Keywords

  • Hepatic fibrosis
  • Hepatic stellate cells
  • Luteolin
  • STAT3

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Luteolin-mediated inhibition of hepatic stellate cell activation via suppression of the STAT3 pathway. / Cummins, Claire B.; Wang, Xiaofu; Nunez Lopez, Omar; Graham, Gabriel; Tie, Hong Yan; Zhou, Jia; Radhakrishnan, Ravi.

In: International Journal of Molecular Sciences, Vol. 19, No. 6, 1567, 01.06.2018.

Research output: Contribution to journalArticle

Cummins, Claire B. ; Wang, Xiaofu ; Nunez Lopez, Omar ; Graham, Gabriel ; Tie, Hong Yan ; Zhou, Jia ; Radhakrishnan, Ravi. / Luteolin-mediated inhibition of hepatic stellate cell activation via suppression of the STAT3 pathway. In: International Journal of Molecular Sciences. 2018 ; Vol. 19, No. 6.
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