Peretinoin is an oral acyclic retinoid with a vitamin A-like structure that targets retinoid nuclear receptors such as retinoid X receptor (RXR) and retinoic acid receptor (RAR)[3]. Peretinoin inhibits HCV RNA amplification and virus release by altering lipid metabolism with a EC50 of 9 μM. Peretinoin treatment of Huh-7 cells reduced mRNA levels, protein expression and enzymatic activity of SPHK1[4]. Peretinoin prevents the progression of NASH (non-alcoholic steatohepatitis) and the development of HCC (hepatocellular carcinoma) through activating the autophagy pathway by increased Atg16L1 expression, which is an essential regulator of autophagy and anti-inflammatory proteins[5]. Peretinoin inhibited the signaling pathways of fibrogenesis, angiogenesis, and Wnt/β-catenin in Pdgf-c transgenic mice. In vitro, peretinoin repressed the expression of PDGF (platelet-derived growth factor) receptors α/β in primary mouse hepatic stellate cells (HSC), hepatoma cells, fibroblasts, and endothelial cells. Peretinoin also inhibited PDGF-C-activated transformation of HSCs into myofibroblasts[6].
Peretinoin 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Human liver cells (HepG2)
1 µM
24 hours
Peretinoin did not alter APOC3 mRNA or secreted APOC3 protein levels in HepG2 cells, whereas cyclic retinoids significantly elevated these levels.
To evaluate the time-dependent effect of Peretinoin on HCV replication across different genotypes. Results showed that Peretinoin suppressed RNA replication in a time-dependent manner for all genotypes tested.
Sci Rep. 2014 Apr 15;4:4688
Huh-7 cells
10, 25, 50 µM
48 hours
Peretinoin significantly reduced mRNA levels, protein expression, and enzymatic activity of SPHK1.
Sci Rep. 2017 Dec 5;7(1):16978
Huh7 cells
10, 20, 30 µM
5 days
Peretinoin strongly repressed the levels of HBV-DNA, cccDNA, and pregenomic RNA without cytotoxicity
Int J Mol Sci. 2018 Jan 23;19(2):108
HepG2.2.15 cells
5, 10, 25, 50 µM
5 days
Peretinoin significantly reduced the levels of intracellular HBV-DNA, nuclear cccDNA, and HBV transcript at a concentration that did not induce cytotoxicity
Int J Mol Sci. 2018 Jan 23;19(2):108
Huh-7.5 cells
5-50 µM
72 hours
To assess the effect of Peretinoin on cell growth. Results showed that the cell numbers were identical under the conditions tested.
Sci Rep. 2014 Apr 15;4:4688
Huh-7.5 cells
1-100 µM
72 hours
To evaluate the inhibitory effect of Peretinoin on HCV RNA replication. Results showed that Peretinoin inhibited the replication of H77S.3/GLuc2A in a dose-dependent manner.
Sci Rep. 2014 Apr 15;4:4688
Primary human valvular interstitial cells (VIC)
1 µM
thoursee weeks
Peretinoin attenuated PM-induced human VIC calcification to a similar extent as ATRA.
DEN-induced hepatoma was fewer and less frequent in SPHK1 knockout mice compared to wild-type mice, indicating a crucial role of SPHK1 in hepatocarcinogenesis.
Sci Rep. 2017 Dec 5;7(1):16978
Human
Patients with HCV-related hepatocellular carcinoma
Oral
600 mg/day or 300 mg/day
Once daily for up to 2 years
To evaluate the effects of Peretinoin on survival in patients with HCV-related hepatocellular carcinoma. Results showed that the 600 mg/day group had significantly longer survival than the placebo group in Child-Pugh A classified patients.
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