title: Modulation of carcinogen metabolizing enzymes by chromanone A; a new chromone derivative from algicolous marine fungus Penicillium sp.
abstract: A marine fungal isolate, Penicillium sp. fungus isolated from seaweed, Ulva sp., led to the isolation of a new chromone derivatives, 2-(hydroxymethyl)-8-methoxy-3-methyl-4H-chromen-4-one (chromanone A). The structure was determined by interpretation of their spectroscopic data (1D and 2D NMR, MS, UV and IR). At the nitiation stage of carcinogenesis, carcinogens is activated by cytochrome P-450 1A (CYP1A) and detoxified by glutathione S-transferases (GST), quinine reductase (QR), and epoxide hydrolase (mEH). We tested the modulatory effect of chromanone A on these carcinogen metabolizing enzymes. The results indicated that chromanone A (4μg/ml) is a promising inhibitor of CYP1A activity up to 60% of the stimulated-CYP1A in murine hepatoma cells (Hepa1c1c7), and it significantly induced GST but not total thiols at low concentrations. Chromanone A had no influence on QR activity, while it resulted in a significant dose-dependant enhancement mEH activity in Hepa1c1c7 cells (P<0.05-0.01). Additionally, chromanone A possessed a potent specific radical scavenging activity against hydroxyl radicals more than peroxyl radicals that may be responsible for the inhibitory effect of chromanone A on the induced-DNA damage in cells. In conclusion, this study proved that chromanone A may act as an active tumor anti-initiating via modulation of carcinogen metabolizing enzymes and protection from DNA damage.
authors.affiliation: Cancer Biology Laboratory, Center of Excellency for Advanced Science, National Research Center, Dokki 12622, Cairo, Egypt.
authors.forename: Amira M
authors.initials: AM
authors.lastname: Gamal-Eldeen
authors.forename: Ahmed
authors.initials: A
authors.lastname: Abdel-Lateff
authors.forename: Tatsufumi
authors.initials: T
authors.lastname: Okino