title: Chrysin: a histone deacetylase 8 inhibitor with anticancer activity and a suitable candidate for the standardization of Chinese propolis.
abstract: Chinese propolis (CP) is a natural product collected by honeybees and a health food raw material. Previous studies have shown that CP exhibits a broad spectrum of biological activities including anticancer, antioxidant, antibacterial, anti-inflammatory, and antiviral activities. The focuses of the present study were the standardization of CP and the possible mechanisms of its active anticancer ingredients. Nine samples of CP were collected from different locations in China. Analyses of the CP samples revealed that all 9 had similar chemical compositions. Parameters analyzed included the CP extract dry weight, total phenolic content, and DPPH free radical scavenging activities. The active anticancer ingredient was isolated, characterized against human MDA-MB-231 breast cancer cells, and identified as chyrsin, a known potent anticancer compound. Chrysin is present at high levels in all 9 of the CP samples, constituting approximately 2.52% to 6.38% of the CP extracts. However, caffeic acid phenethyl ester (CAPE), another potent active ingredient is present in low levels in 9 samples of CP, constituting approximately 0.08% to 1.71% of the CP extracts. Results from analyses of enzymatic activity indicated that chrysin is a histone deacetylase inhibitor (HDACi) and that it markedly inhibited HDAC8 enzymatic activity (EC(50) = 40.2 μM). In vitro analyses demonstrated that chrysin significantly suppressed cell growth and induced differentiation in MDA-MB-231 cells. In a xenograft animal model (MDA-MB-231 cells), orally administered chrysin (90 mg/kg/day) significantly inhibited tumor growth. Despite the geographical diversity of the 9 samples' botanical origins, their chemical compositions and several analyzed parameters were similar, suggesting that CP is standardized, with chrysin being the major active ingredient. Overall, in vitro and in vivo data indicated that chrysin is an HDAC8 inhibitor, which can significantly inhibit tumor growth. Data also suggested that chrysin might represent a suitable candidate for standardization of CP.
authors.affiliation: Bee Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100093, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Sun
authors.forename: Ai-Ling
authors.initials: AL
authors.lastname: Chen
authors.forename: Hsiao-Chiao
authors.initials: HC
authors.lastname: Hung
authors.forename: Yin-Huan
authors.initials: YH
authors.lastname: Chien
authors.forename: Jing-Shi
authors.initials: JS
authors.lastname: Huang
authors.forename: Chung-Yang
authors.initials: CY
authors.lastname: Huang
authors.forename: Yue-Wen
authors.initials: YW
authors.lastname: Chen
authors.forename: Chia-Nan
authors.initials: CN
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D002681:China; D004791:Enzyme Inhibitors; D005260:Female; D005419:Flavonoids / Q000032:analysis* / Q000302:isolation & purification / Q000494:pharmacology; D006655:Histone Deacetylases; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011429:Propolis / Q000737:chemistry* / Q000592:standards*; D012097:Repressor Proteins / Q000037:antagonists & inhibitors*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D005419:Flavonoids; D012097:Repressor Proteins; C043561:chrysin; D011429:Propolis; C409470:HDAC8 protein, human; D006655:Histone Deacetylases