Bioactivation of the phytoestrogen diosmetin by CYP1 cytochromes P450

Androutsopoulos, Vasilis P.; Wilsher, Nicola E.; Arroo, R. R. J.; Potter, Gerard A.

doi:10.1016/j.canlet.2008.08.032

Cited by 71 publications

(69 citation statements)

References 36 publications

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“…According to our previous findings diosmetin was metabolized to luteolin and another unidentified metabolite by microsomes expressing human CYP1 enzymes (10). In addition luteolin was the main conversion product of the metabolism of diosmetin, in MCF-7 cells pretreated for 24 h with the potent CYP1 inducer TCDD (10). In agreement with these findings, the present study revealed that diosmetin is also metabolized to luteolin in MDA-MB 468 cell cultures.…”

Section: Discussionsupporting

confidence: 92%

“…It has been demonstrated to inhibit proliferation of SCC-9 human oral squamous carcinoma cells, block DMBA-induced DNA adduct formation and cytotoxicity in MCF-7 cells, as well as inhibit CYP1A1 and CYP1B1 EROD activity (11)(12)(13). According to our previous findings diosmetin was metabolized to luteolin and another unidentified metabolite by microsomes expressing human CYP1 enzymes (10). In addition luteolin was the main conversion product of the metabolism of diosmetin, in MCF-7 cells pretreated for 24 h with the potent CYP1 inducer TCDD (10).…”

Section: Discussionmentioning

confidence: 90%

“…A recent study from our group has identified diosmetin as a CYP1 substrate (10). Metabolism of this compound in human breast adenocarcinoma MCF-7 cells, preinduced with the potent CYP1 inducer TCDD, caused enhanced inhibition of cell proliferation (10).…”

Section: Introductionmentioning

confidence: 99%

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Anticancer effects of the flavonoid diosmetin on cell cycle progression and proliferation of MDA-MB 468 breast cancer cells due to CYP1 activation

Arroo¹

2009

Oncol Rep

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Abstract. 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 G 1 arrest at 10 μM 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.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 90%

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Anticancer effects of the flavonoid diosmetin on cell cycle progression and proliferation of MDA-MB 468 breast cancer cells due to CYP1 activation

Arroo¹

2009

Oncol Rep

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“…1 that the only difference between DIOS and luteolin is the 4 0 -O-methyl moiety. Previous studies showed that DIOS can be metabolized to luteolin in liver cells both in vitro and in vivo, the demethylation is catalyzed by CYP1 isoenzymes [37,38]. On the other hand, recent in vivo investigations highlighted that luteolin is a substrate of the catechol-O-methyl transferase (COMT) enzyme and interestingly the most preferable reaction is its 4 0 -O-methylation which results in the formation of DIOS [39,40].…”

Section: Effects Of Flavonoid Aglycones On Atp Levels Of Mdck Cellsmentioning

confidence: 99%

Flavonoid diosmetin increases ATP levels in kidney cells and relieves ATP depleting effect of ochratoxin A

Poór

Veres

Jakus

et al. 2014

Journal of Photochemistry and Photobiology B: Biology

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a b s t r a c tDiosmetin (DIOS) is a flavone aglycone commonly occurring in citrus species and olive leaves, in addition it is one of the active ingredients of some medications. Based on both in vitro and in vivo studies several beneficial effects are attributed to DIOS but the biochemical background of its action seems to be complex and it has not been completely explored yet. Previous investigations suggest that most of the flavonoid aglycones have negative effect on ATP synthesis in a dose dependent manner. In our study 17 flavonoids were tested and interestingly DIOS caused a significant elevation of intracellular ATP levels after 6-and 12-h incubation in MDCK kidney cells. In order to understand the mechanism of action, intracellular ATP and protein levels, ATP/ADP ratio, cell viability and ROS levels were determined after DIOS treatment. In addition, impacts of different enzyme inhibitors and effect of DIOS on isolated rat liver mitochondria were also tested. Finally, the influence of DIOS on the ATP depleting effect of the mycotoxin, ochratoxin A was also investigated. Our major conclusions are the followings: DIOS increases intracellular ATP levels both in kidney and in liver cells. Inhibition of glycolysis or citric acid cycle does not decrease the observed effect. DIOS-induced elevation of ATP levels is completely abolished by the inhibition of ATP synthase. DIOS is able to completely reverse the ATP-depleting effect of the mycotoxin, ochratoxin A. Most probably the DIOS-induced impact on ATP system does not originate from the antioxidant property of DIOS. Based on our findings DIOS may be promising agent to positively influence ATP depletion caused by some metabolic poisons.

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“…Парадоксальность такой ситуации объясняют участием цитохромов в биотрансформации самих полифенолов [44]. Некоторые из них (например, флавоноиды эупаторин и диосметин) являются субстратами цитохромов [45,46]. Особый интерес к таким соединениям вызван тем, что их метаболиты оказывают цитотоксическое действие по отношению к раковым клеткам даже более выраженное, чем исходные вещества.…”

Section: рисунокunclassified

Mechanisms of plant polyphenols anti-cancer effects I. Blockade of carcinogenesis initiation

Spasov

2012

BIOMED KHIM

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Mechanisms of anti-cancer effects of polyphenols, found in fruits, vegetables, spices and representing parts of daily nutrition, have been considered. These compounds may be the basis for development of cancer preventive preparations. They can block carcinogenesis initiation by inactivation of exogenous or endogenous genotoxic molecules including reactive oxygen species. Another mechanism consists in inhibition of activity and synthesis of carcinogen-metabolizing enzymes. Plant polyphenols also induce expression of antioxidant and detoxification enzymes genes.

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Bioactivation of the phytoestrogen diosmetin by CYP1 cytochromes P450

Cited by 71 publications

References 36 publications

Anticancer effects of the flavonoid diosmetin on cell cycle progression and proliferation of MDA-MB 468 breast cancer cells due to CYP1 activation

Anticancer effects of the flavonoid diosmetin on cell cycle progression and proliferation of MDA-MB 468 breast cancer cells due to CYP1 activation

Flavonoid diosmetin increases ATP levels in kidney cells and relieves ATP depleting effect of ochratoxin A

Mechanisms of plant polyphenols anti-cancer effects I. Blockade of carcinogenesis initiation

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