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Suppressive Effects of Novel Oridonin Derivative CYD0625 on Activated Hepatic Stellate Cells
Author(s) -
Wang Xiaofu,
Boha Fredrick,
Kandathiparampil Arlene,
Rastellini Cristiana,
Ding Chunyong,
Ding Ye,
Zhou Jia,
Radhakrishnan Ravi
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.611.5
Subject(s) - hepatic stellate cell , fibronectin , apoptosis , propidium iodide , extracellular matrix , chemistry , cell growth , cell cycle , microbiology and biotechnology , myofibroblast , cell culture , cell , fibrosis , biology , biochemistry , programmed cell death , pathology , medicine , endocrinology , genetics
The natural compound oridonin has been proven to possess anti‐neoplastic and anti‐inflammatory properties. Previously, we described that oridonin caused apoptosis, inhibition of cell proliferation and down‐regulation of extracellular matrix proteins (ECM) in activated hepatic stellate cells (HSC). In this study, we investigated the potentially more potent derivative CYD0625 in vitro . Methods Cell proliferation was measured by Alamar Blue assay. Cell apoptosis was detected by staining with Yo‐Pro‐1 and propidium iodide. Immunoblot and immunofluorescence staining were performed for cellular protein expression. Results Treatment of CYD0625 significantly inhibited LX‐2 cells proliferation in a dose‐ and time‐dependent manner with ~20–fold greater potency than oridonin. Similar results were observed in HSC‐T6 cells, whereas 1 μM of CYD0625 treatment had no effect on the human hepatocyte cell line C3A. CYD0625 induced LX‐2 cells apoptosis and S‐phase cell cycle arrest, and it was associated with activation of cell cycle inhibitory proteins p21, p16. The myofibroblast marker protein α‐smooth muscle actin and major ECM proteins collagen type I and fibronectin were markedly down‐regulated by CYD0625. Interestingly, treatment of HSC with CYD0625 at a low dosage (0.1 μM), significantly suppressed collagen type I expression in LX‐2 cells. Furthermore, pre‐treatment with CYD0625 blocked PDGF‐BB‐induced collagen type I and fibronectin expression in LX‐2 cells.Conclusion In comparison with oridonin, its novel derivative CYD0625 could be a more potent and safer hepatic anti‐fibrosis agent.