The NADPH Oxidase Inhibitor Apocynin Suppresses Preneoplastic Liver Foci of Rats.

Abstract	Reactive oxygen species (ROS) have been revealed to be important factors for carcinogenesis and tumor progression. Therefore, we focused on an ROS-generating protein, nicotinamide adenine dinucleotide phosphate oxidase, and evaluated whether its inhibitor, apocynin, could suppress hepatocarcinogenesis in a medium-term rat liver bioassay. The number and size of glutathione S-transferase placental form (GST-P)-positive foci were significantly reduced by apocynin in a dose-dependent manner. The reduction of ROS generation by apocynin was confirmed by dihydroethidium staining. Apocynin treatment also significantly reduced Ki-67 positivity, downregulated cyclooxygenase 2, and suppressed the activation of the c-Myc pathway. Meanwhile, ROS generation was not different between GST-P-positive foci and surrounding GST-P-negative areas of the liver. In conclusion, the present data suggest that apocynin possesses a potential antihepatocarcinogenic property.
Authors	Satoshi Fuji, Shugo Suzuki, Aya Naiki-Ito, Hiroyuki Kato, Masashi Hayakawa, Yoriko Yamashita, Toshiya Kuno, Satoru Takahashi
Journal	Toxicologic pathology (Toxicol Pathol) Vol. 45 Issue 4 Pg. 544-550 (06 2017) ISSN: 1533-1601 [Electronic] United States
PMID	28573935 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Acetophenones Anticarcinogenic Agents Ccnd1 protein, rat Ki-67 Antigen Reactive Oxygen Species Cyclin D1 acetovanillone Cyclooxygenase 2 Ptgs2 protein, rat NADPH Oxidases Glutathione Transferase
Topics	Acetophenones (pharmacology) Animals Anticarcinogenic Agents (pharmacology) Body Weight Carcinogenesis (drug effects) Cell Proliferation (drug effects) Cyclin D1 (genetics, metabolism) Cyclooxygenase 2 (genetics, metabolism) Gene Expression Regulation Glutathione Transferase (metabolism) Ki-67 Antigen (genetics, metabolism) Liver (drug effects, metabolism) Liver Neoplasms, Experimental (chemically induced, prevention & control) Male NADPH Oxidases (antagonists & inhibitors, genetics, metabolism) Organ Size (drug effects) Rats Rats, Inbred F344 Reactive Oxygen Species (metabolism)

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