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Pharmaceutical and nutraceutical approaches for preventing liver carcinogenesis: Chemoprevention of hepatocellular carcinoma using acyclic retinoid and branched‐chain amino acids
Author(s) -
Shimizu Masahito,
Shirakami Yohei,
Hanai Tatsunori,
Imai Kenji,
Suetsugu Atsushi,
Takai Koji,
Shiraki Makoto,
Moriwaki Hisataka
Publication year - 2014
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201300538
Subject(s) - hepatocellular carcinoma , retinoid , cirrhosis , medicine , cancer research , carcinogenesis , malignancy , oncology , pharmacology , endocrinology , cancer , biology , biochemistry , retinoic acid , gene
The poor prognosis for patients with hepatocellular carcinoma ( HCC ) is associated with its high rate of recurrence in the cirrhotic liver. Therefore, more effective strategies need to be urgently developed for the chemoprevention of this malignancy. The malfunction of retinoid X receptor α, a retinoid receptor, due to phosphorylation by R as/mitogen‐activated protein kinase is closely associated with liver carcinogenesis and may be a promising target for HCC chemoprevention. Acyclic retinoid ( ACR ), a synthetic retinoid, can prevent HCC development by inhibiting retinoid X receptor α phosphorylation and improve the prognosis for this malignancy. Supplementation with branched‐chain amino acids ( BCAA ), which are used to improve protein malnutrition in patients with liver cirrhosis, can also reduce the risk of HCC in obese cirrhotic patients. In experimental studies, both ACR and BCAA exert suppressive effects on HCC development and the growth of HCC cells. In particular, combined treatment with ACR and BCAA cooperatively inhibits the growth of HCC cells. Furthermore, ACR and BCAA inhibit liver tumorigenesis associated with obesity and diabetes, both of which are critical risk factors for HCC development. These findings suggest that pharmaceutical and nutraceutical approaches using ACR and BCAA may be promising strategies for preventing HCC and improving the prognosis of this malignancy.