title: 2'-Hydroxyflavanone: A promising molecule for kidney cancer prevention.
abstract: Kidney cancer, also known as renal cell carcinoma (RCC), is one of the top 10 diagnosed cancers in the USA, and the incidence is rising. Despite major improvements in drug therapy strategies, RCC remains a deadly malignancy if not found and removed in its early stages. RCC is so highly drug-resistant that no effective life-prolonging regimen of cytotoxic chemotherapy has been demonstrated for RCC, despite several decades of effort. It is also highly radiation-resistant, thus circumventing therapies to prevent local recurrence or to control metastatic disease. In the last few years, extensive research has been conducted to elucidate the functional significance of the plant-derived compounds, and their derivatives, as anticancer agents. This review is focussed on a chemo-dietary prevention strategy against RCC using a citrus-derived compound called 2'-hydroxyflavanone. RCC is frequently caused by VHL gene mutations, which contribute to 75% of all RCCs. These mutations are positively linked to cigarette smoking, and exposure to the tobacco carcinogen, N-nitrosodimethylamine and benzopyrene, can disrupt VHL. According to in vitro and preclinical mouse studies, 2'-hydroxyflavanone can both protect the VHL locus and prevent the progression of VHL-mutant cancer. Human clinical trials examining the effect of supplementation of 2'-hydroxyflavanone, either alone or in combination with chemotherapeutic drugs, on RCC prevention have not been conducted, although there is considerable potential for 2'-hydroxyflavanone and its derivatives to be developed as RCC chemoprevention agents. Therefore, the discovery of plant-derived cancer therapies, such as 2'-hydroxyflavanone, offers a new strategy for combating this highly resistant cancer.
authors.affiliation: Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute, City of Hope, Comprehensive Cancer Center, Duarte, CA 91010, United States. Electronic address: ssinghal@coh.org.
authors.forename: Sharad S
authors.initials: SS
authors.lastname: Singhal
authors.affiliation: Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute, City of Hope, Comprehensive Cancer Center, Duarte, CA 91010, United States.
authors.forename: Jyotsana
authors.initials: J
authors.lastname: Singhal
authors.affiliation: Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute, City of Hope, Comprehensive Cancer Center, Duarte, CA 91010, United States.
authors.forename: James L
authors.initials: JL
authors.lastname: Figarola
authors.affiliation: Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute, City of Hope, Comprehensive Cancer Center, Duarte, CA 91010, United States.
authors.forename: Arthur
authors.initials: A
authors.lastname: Riggs
authors.affiliation: Department of Molecular Medicine, Beckman Research Institute, City of Hope, Comprehensive Cancer Center, Duarte, CA 91010, United States.
authors.forename: David
authors.initials: D
authors.lastname: Horne
authors.affiliation: Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute, City of Hope, Comprehensive Cancer Center, Duarte, CA 91010, United States; Department of Medical Oncology, Beckman Research Institute, City of Hope, Comprehensive Cancer Center, Duarte, CA 91010, United States.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Awasthi
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001580:Benzopyrenes / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity; D002292:Carcinoma, Renal Cell / Q000139:chemically induced / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D004128:Dimethylnitrosamine / Q000633:toxicity; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D044950:Flavanones / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D009154:Mutation; D015398:Signal Transduction; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: C520534:2'-hydroxyflavanone; D000972:Antineoplastic Agents, Phytogenic; D001580:Benzopyrenes; D002273:Carcinogens; D044950:Flavanones; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human; D004128:Dimethylnitrosamine
keywords: 2-Hydroxyflavanone; Aldo-keto reductase; Chemoprevention; Glutathione-S-transferase; Renal cell carcinoma; von Hippel–Lindau