Anticancer effects of the flavonoid diosmetin on cell cycle progression and proliferation of MDA-MB 468 breast cancer cells due to CYP1 activation.
Flavonoids constitute a large class of polyphenolic compounds with cancer preventative properties. We have examined the ability of the natural flavone diosmetin to inhibit proliferation of breast adenocarcinoma MDA-MB 468 and normal breast MCF-10A cells and found that this compound is selective for the cancer cells with slight toxicity in the normal breast cells. Diosmetin was metabolised to the structurally similar flavone luteolin in MDA-MB 468 cells, whereas no metabolism was seen in MCF-10A cells. Diosmetin caused G1 arrest at 10 microM in MDA-MB 468 cells after 48-h treatment whereas this effect was not observed in MCF-10A cells. We suggest that diosmetin exerts cytostatic effects in MDA-MB 468 cells, due to CYP1A1 and CYP1B1 catalyzed conversion to the flavone luteolin.
Leicester School of Pharmacy, De Montfort University, The Gateway, Leicester, LE1 9BH, UK.
Vasilis P
VP
Androutsopoulos
Sachin
S
Mahale
Randolph R J
RR
Arroo
Gerry
G
Potter
D000230:Adenocarcinoma / Q000201:enzymology / Q000473:pathology*; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases; D001711:Biotransformation; D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism*; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D005419:Flavonoids / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D047311:Luteolin / Q000378:metabolism / Q000494:pharmacology; D010865:Pilot Projects
D000970:Antineoplastic Agents; D020536:Enzyme Activators; D005419:Flavonoids; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D047311:Luteolin; C039602:diosmetin