Abstract
BackgroundAlthough cisplatin is one of the most effective chemotherapeutic agents, cisplatin alone does not achieve a satisfactory therapeutic outcome. Also cisplatin accumulation shows toxicity to normal tissues. In this study, we examined the possibility of HemoHIM both to enhance anticancer effect with cisplatin and to reduce the side effects of cisplatin in melanoma-bearing mice.MethodsHemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of 3 edible herbs, Angelica Radix, Cnidium Rhizoma and Paeonia Radix. Anticancer effects of HemoHIM with cisplatin were evaluated in melanoma-bearing mice. We used a Cr51-release assay to measure the activity of NK/Tc cell and ELISA to evaluate the production of cytokines.ResultsIn melanoma-bearing mice, cisplatin (4 mg/kg B.W.) reduced the size and weight of the solid tumors, and HemoHIM supplementation with cisplatin enhanced the decrease of both the tumor size (p < 0.1) and weight (p < 0.1). HemoHIM itself did not inhibit melanoma cell growth in vitro, and did not disturb the effects of cisplatin in vitro. However HemoHIM administration enhanced both NK cell and Tc cell activity in mice. Interestingly, HemoHIM increased the proportion of NK cells in the spleen. In melanoma-bearing mice treated with cisplatin, HemoHIM administration also increased the activity of NK cells and Tc cells and the IL-2 and IFN-γ secretion from splenocytes, which seemed to contribute to the enhanced efficacy of cisplatin by HemoHIM. Also, HemoHIM reduced nephrotoxicity as seen by tubular cell of kidney destruction.ConclusionHemoHIM may be a beneficial supplement during cisplatin chemotherapy for enhancing the anti-tumor efficacy and reducing the toxicity of cisplatin.
Highlights
Cisplatin is one of the most effective chemotherapeutic agents, cisplatin alone does not achieve a satisfactory therapeutic outcome
Our results suggest that HemoHIM may be a beneficial supplement during cisplatin chemotherapy by enhancing the anti-tumor efficacy and reducing the toxicity of cisplatin
HemoHIM supplementation without cisplatin showed no reduction in tumor weight [6.15 g (± 1.238)] when compared with the control group (Data not shown)
Summary
Cisplatin is one of the most effective chemotherapeutic agents, cisplatin alone does not achieve a satisfactory therapeutic outcome. In many cases, chemotherapy or radiotherapy alone cannot achieve a satisfactory therapeutic outcome, namely the complete remission of tumors, and induces severe side effects at therapeutically effective doses. Cisplatin (cis-diaminedichloroplatinum (II) or CDDP), a platinum-containing anticancer drug, is one of the most commonly used cytotoxic agents for the treatment of a variety of solid malignant tumors. The precise mechanism for the cisplatin-induced toxicity is not well understood, cisplatin is preferentially taken up and accumulated in the liver and kidney cells [3], resulting in the enhanced production of reactive oxygen species (ROS) and the decrease in antioxidant enzymes [4,5,6,7]. Antioxidants have been administered before cisplatin treatment to protect against nephrotoxicity [8,9,10]
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