title: Pharmaceutical and nutraceutical approaches for preventing liver carcinogenesis: chemoprevention of hepatocellular carcinoma using acyclic retinoid and branched-chain amino acids.
abstract: 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 Ras/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.
authors.affiliation: Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Shimizu
authors.forename: Yohei
authors.initials: Y
authors.lastname: Shirakami
authors.forename: Tatsunori
authors.initials: T
authors.lastname: Hanai
authors.forename: Kenji
authors.initials: K
authors.lastname: Imai
authors.forename: Atsushi
authors.initials: A
authors.lastname: Suetsugu
authors.forename: Koji
authors.initials: K
authors.lastname: Takai
authors.forename: Makoto
authors.initials: M
authors.lastname: Shiraki
authors.forename: Hisataka
authors.initials: H
authors.lastname: Moriwaki
mesh_terms: D000597:Amino Acids, Branched-Chain / Q000494:pharmacology / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000517:prevention & control*; D002908:Chronic Disease; D002986:Clinical Trials as Topic; D019587:Dietary Supplements; D006801:Humans; D008107:Liver Diseases / Q000188:drug therapy; D008113:Liver Neoplasms / Q000378:metabolism / Q000517:prevention & control*; D010766:Phosphorylation; D047490:Retinoid X Receptor alpha / Q000378:metabolism; D047488:Retinoid X Receptors / Q000378:metabolism; D012176:Retinoids / Q000737:chemistry / Q000627:therapeutic use; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000597:Amino Acids, Branched-Chain; D047490:Retinoid X Receptor alpha; D047488:Retinoid X Receptors; D012176:Retinoids; D014212:Tretinoin; C034534:3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid
keywords: Acyclic retinoid; Branched-chain amino acid; Chemoprevention; Hepatocellular carcinoma; Obesity