TY - JOUR
T1 - Epigallocatechin Gallate Induces Hepatic Stellate Cell Senescence and Attenuates Development of Hepatocellular Carcinoma
AU - Sojoodi, Mozhdeh
AU - Wei, Lan
AU - Erstad, Derek J.
AU - Yamada, Suguru
AU - Fujii, Tsutomu
AU - Hirschfield, Hadassa
AU - Kim, Rosa S.
AU - Lauwers, Gregory Y.
AU - Lanuti, Michael
AU - Hoshida, Yujin
AU - Tanabe, Kenneth K.
AU - Fuchs, Bryan C.
N1 - Funding Information:
This work was supported by an Investigator-Initiated Grant from the American Institute for Cancer Research (to B.C. Fuchs).
Funding Information:
K.K. Tanabe reports a patent to Prevention of fibrosis and hepatocellular carcinoma issued and research support from Enanta Pharmaceuticals and Zafgen to study drugs to prevent HCC. B.C. Fuchs reports receiving grants from American Institute for Cancer Research during the conduct of the study; grants from Blade Therapeutics, Collagen Medical, and Enanta Pharmaceuticals, and personal fees from Gilead Sciences and Ferring Pharmaceuticals outside the submitted work. No potential conflicts of interest were disclosed by the other authors.
Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - Hepatocellular carcinoma (HCC) is a highly morbid condition with lack of effective treatment options. HCC arises from chronically inflamed and damaged liver tissue; therefore, chemoprevention may be a useful strategy to reduce HCC incidence. Several reports suggest that epigallocatechin gallate (EGCG), extracted from green tea, can suppress liver inflammation and fibrosis in animal models, but its role in HCC chemoprevention is not well established. In this study, male Wistar rats were injected with diethylnitrosamine at 50 mg/kg for 18 weeks to induce cirrhosis and HCC, and EGCG was given in drinking water at a concentration of 0.02%. Clinically achievable dosing of EGCG was well-tolerated in diethylnitrosamine-injured rats and was associated with improved serum liver markers including alanine transaminase, aspartate transaminase, and total bilirubin, and reduced HCC tumor formation. Transcriptomic analysis of diethylnitrosamine-injured hepatic tissue was notable for increased expression of genes associated with the Hoshida high risk HCC gene signature, which was prevented with EGCG treatment. EGCG treatment also inhibited fibrosis progression, which was associated with inactivation of hepatic stellate cells and induction of the senescence-associated secretory phenotype. In conclusion, EGCG administered at clinically safe doses exhibited both chemopreventive and antifibrotic effects in a rat diethylnitrosamine liver injury model.
AB - Hepatocellular carcinoma (HCC) is a highly morbid condition with lack of effective treatment options. HCC arises from chronically inflamed and damaged liver tissue; therefore, chemoprevention may be a useful strategy to reduce HCC incidence. Several reports suggest that epigallocatechin gallate (EGCG), extracted from green tea, can suppress liver inflammation and fibrosis in animal models, but its role in HCC chemoprevention is not well established. In this study, male Wistar rats were injected with diethylnitrosamine at 50 mg/kg for 18 weeks to induce cirrhosis and HCC, and EGCG was given in drinking water at a concentration of 0.02%. Clinically achievable dosing of EGCG was well-tolerated in diethylnitrosamine-injured rats and was associated with improved serum liver markers including alanine transaminase, aspartate transaminase, and total bilirubin, and reduced HCC tumor formation. Transcriptomic analysis of diethylnitrosamine-injured hepatic tissue was notable for increased expression of genes associated with the Hoshida high risk HCC gene signature, which was prevented with EGCG treatment. EGCG treatment also inhibited fibrosis progression, which was associated with inactivation of hepatic stellate cells and induction of the senescence-associated secretory phenotype. In conclusion, EGCG administered at clinically safe doses exhibited both chemopreventive and antifibrotic effects in a rat diethylnitrosamine liver injury model.
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U2 - 10.1158/1940-6207.CAPR-19-0383
DO - 10.1158/1940-6207.CAPR-19-0383
M3 - Article
C2 - 32253266
AN - SCOPUS:85085903989
SN - 1940-6207
VL - 13
SP - 497
EP - 508
JO - Cancer Prevention Research
JF - Cancer Prevention Research
IS - 6
ER -