Quercetin and hyperthermia modulate cisplatin-induced DNA damage in tumor and normal tissues in vivo.

Nephrotoxicity, hepatotoxicity, myelosuppression, and genotoxicity are the major limitation for the clinical use of cisplatin as an anti-tumoural drug. Hyperthermia enhances the clastogenicity of cisplatin. In addition, hyperthermia is a promising approach for cancer therapy because it not only kills cancer cells directly, but also activates anti-cancer immunity as an indirect effect. The aim of this study was to determine whether preventive treatment with quercetin (QU) can reduce cisplatin-induced DNA damage in liver, kidney and blood cells and whether QU has the potential to serve as a beneficial supplement before cisplatin hyperthermal intraperitoneal chemotherapy (HIPEC) in order to gain immunomodulatory responses of mice to the tumor. Preventive treatment of mice with QU (50 mg kg(-1)) had a protective effect on cisplatin-induced DNA damage in normal cells, except kidney cells, in both normothermic and hyperthermic conditions without interfering with the antitumor efficacy of the combined regimen. Immunostimulation by QU is stressed as an important factor in the tumor-inhibiting effect of hyperthermia in addition to the well known selective heat killing of neoplastic cells. In conclusion, these results suggested that preventive treatment with QU could protect the blood, liver and kidney cells of mice against HIPEC-induced injury and increase survival of mice by improving the antitumor adaptive immunity with hyperthermia.

WITHDRAWN: Quercetin enhances the effect of hyperthermal intraperitoneal chemotherapy with cisplatin in mice.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1177/0960327113499048. The duplicate article has therefore been withdrawn.

Synergism between propolis and hyperthermal intraperitoneal chemotherapy with cisplatin on ehrlich ascites tumor in mice.

We investigated antitumor, genotoxic, chemopreventive, and immunostimulative effects of local chemoimmunotherapy and hyperthermal intraperitoneal chemotherapy (HIPEC) in a mouse-bearing Ehrlich ascites tumor (EAT). Mice were treated with water-soluble derivative of propolis (WSDP) at a dose of 50 mg kg(-1) , 7 and 3 days before implantation of EAT cells, whereas cisplatin (5 or 10 mg kg(-1) ) was injected 3 days after implantation of EAT cells at 37°C and 43°C. The following variables were analyzed: the total number of cells, differential count of the cells present in the peritoneal cavity, functional activity of macrophages, comet assay, and micronucleus assay. The combination of WSDP + CIS 5 mg kg(-1) at 37°C resulted in tumor growth inhibition and increased the survival of mice by additional 115.25%. WSDP with HIPEC increased the survival of mice by additional 160.3% as compared with HIPEC. WSDP reduced cisplatin toxic and genotoxic effect to normal cells without affecting cisplatin cytotoxicity on EAT cells. In addition, WSDP with HIPEC increased the cytotoxic actions of macrophages to tumor cells. Water-soluble derivative of propolis increases macrophage activity and sensitivity of tumor cells to HIPEC and reduces cisplatin toxicity to normal cells.