Synergistic effects of flavonoids and ascorbate on enhancement in DNA degradation induced by a bleomycin-Fe complex.
Flavonoids were examined for synergistic effects with ascorbate on enhancement of DNA degradation induced by a bleomycin(BLM)-Fe complex. The synergistic effects of flavonoids and ascorbate on DNA degradation induced by the BLM-Fe complex were observed to be greater with flavonoids such as isorhamnetin, kaempferol and morin, which accelerated oxidation more markedly in the presence, than in the absence of BLM. Conversely, myricetin and fisetin, which showed oxidation barely accelerated by the addition of BLM, inhibited DNA degradation promoted by ascorbate. Consequently, there was a good correlation between oxidation of flavonoids accelerated by BLM and the extent of DNA degradation promoted synergistically with ascorbate. Our previous studies indicated that oxidation of flavonoids accelerated by BLM and DNA degradation promoted by flavonoids were not correlated with Fe(III)-reducing activity of flavonoids. Those results suggest that Fe(III)-reducing activity of flavonoids is not the only factor determining DNA degradation-promoting activity induced by the BLM-Fe complex. On the other hand, in a Fenton reaction, degradation of 2-deoxy-d-ribose promoted by flavonoids was correlated to the Fe(III)-reducing activity of flavonoids. However, there was not a synergistic interaction between flavonoids and ascorbate in the degradation of 2-deoxy-d-ribose. Therefore, it is suggested that the synergistic DNA degradation caused by flavonoids and ascorbate in the BLM-Fe redox cycle arose from the difference in the reductive processes in which flavonoids and ascorbate mainly act.
Sugihara
Narumi
N
Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Gakuen-cho, Fukuyama, Hiroshima 729-0292, Japan. sugihara@fupharm.fukuyama-u.ac.jp
Kaneko
Arisa
A
Furuno
Koji
K
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology*; D001761:Bleomycin / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism*; D003855:Deoxyribose / Q000378:metabolism; D004357:Drug Synergism; D005296:Ferrous Compounds / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D010084:Oxidation-Reduction; D012474:Salmon
D000903:Antibiotics, Antineoplastic; D005296:Ferrous Compounds; D005419:Flavonoids; D001761:Bleomycin; D003855:Deoxyribose; D004247:DNA; D001205:Ascorbic Acid