Enhancement of the antiproliferative activity of cis-diamminedichloroplatinum(II) by quercetin.
We have shown previously that the flavonoid quercetin (3,3',4',5,7-pentahydroxyflavone) enhances the antiproliferative activity of cis-diamminedichloroplatinum(II) (cis-DDP) in vitro. In order to investigate whether this observation could be exploited in cancer treatment, we tested this drug combination in human tumor xenografts. The established human large-cell cancer of the lung (LXFL 529) was implanted s.c. into nude mice. Tumors were allowed to grow to a mean diameter of approximately 5 mm and the animals were subsequently treated intraperitoneally with quercetin, cis-DDP or a combination of both. Treatment was given 3 times at 3-day intervals. Twenty milligrams quercetin per kg body weight caused no inhibition in tumor growth compared to untreated controls; 3 mg cis-DDP per kg body weight with the same time schedule reduced tumor growth, compared to quercetin-treated and control animals. Concomitant treatment with 20 mg quercetin and 3 mg cis-DDP per kg body weight reduced tumor growth to a significantly greater degree than cis-DDP alone. Toxicity of this treatment was relatively low as determined by measurements of the body weight of the mice. A combination of 4 mg or 5 mg cis-DDP with 20 mg quercetin per kg body weight also reduced tumor growth compared to single cis-DDP treatment. The toxicity of treatment with these increased doses was high, as shown by the high lethality and the loss of body weight of surviving animals.
Hofmann
J
J
Institute of Medicinal Chemistry and Biochemistry, University of Innsbruck, Austria.
Fiebig
H H
HH
Winterhalter
B R
BR
Berger
D P
DP
Grunicke
H
H
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D018288:Carcinoma, Small Cell / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004357:Drug Synergism; D005419:Flavonoids / Q000627:therapeutic use*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011794:Quercetin / Q000008:administration & dosage / Q000627:therapeutic use*
D005419:Flavonoids; D011794:Quercetin; D002945:Cisplatin