title: Raspberry pulp polysaccharides inhibit tumor growth via immunopotentiation and enhance docetaxel chemotherapy against malignant melanoma in vivo.
abstract: It has been reported previously that the systemic efficacy of chemotherapeutic agents is substantially restricted for some cancer types, including malignant melanoma. Therefore, the development of more effective treatment modalities remains a critical, albeit elusive, goal in anticancer therapy. The study presented here evaluates the antitumor activity of raspberry pulp polysaccharides (RPPs) against malignant melanoma using a murine tumor-bearing model. Furthermore, the underlying mechanism of this antitumor activity has also been investigated. The results show that while RPP exhibits no direct cytotoxic effect on HT-29, MGC-803, HeLa, Bel-7402, L02 and B16F10 cells in vitro, it does demonstrate a dose-dependent growth inhibition of melanoma in vivo with an inhibition ratio of 59.95% at a dose of 400 mg kg(-1). Besides this, the body weight and spleen index in tumor-bearing mice have also been improved in RPP-treated groups. RPP is also found to induce splenocyte proliferation and is able to upregulate the activity of immune-related enzymes, including acid phosphatase (ACP), alkaline phosphatase (AKP), lactate dehydrogenase (LDH) and superoxide dismutase (SOD) in the spleen of tumor-bearing mice. The levels of tumor necrosis factor α (TNF-α), interferon γ (IFN-γ) and interleukin 2 (IL-2) in the serum of tumor-bearing mice show to be effectively increased upon RPP treatment. Histopathological analyses show that RPP induces tumor tissue necrosis by increasing inflammatory cell infiltration and causes no lesions to liver and kidney tissues. Remarkably, RPP further enhances the antitumor effect of the chemotherapeutic drug docetaxel and alleviates docetaxel-induced liver and kidney lesions in tumor-bearing mice. These findings indicate that RPP exhibits antitumor activity in vivo against malignant melanoma, partly by enhancing the cellular immune response of the host organism. In summary, RPP features critical properties to potentially find use as an immunopotentiating agent or as a chemotherapy adjuvant agent for the treatment of malignant melanoma.
authors.affiliation: Northwest Institute of Plateau Biology, Chinese Academy of Sciences, No. 23, Xinning road, 810001 Xining, Qinghai, PR China. yrsuo@nwipb.cas.cn.
authors.forename: Yong-Jing
authors.initials: YJ
authors.lastname: Yang
authors.forename: Han-Mei
authors.initials: HM
authors.lastname: Xu
authors.forename: You-Rui
authors.initials: YR
authors.lastname: Suo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D049109:Cell Proliferation / Q000187:drug effects*; D000077143:Docetaxel; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010936:Plant Extracts / Q000008:administration & dosage*; D011134:Polysaccharides / Q000008:administration & dosage*; D065856:Rubus / Q000737:chemistry*; D012878:Skin Neoplasms; D043823:Taxoids / Q000008:administration & dosage*; D047368:Tumor Burden / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014866:Waste Products / Q000032:analysis*; D000096142:Cutaneous Malignant Melanoma
chemical_list: D000970:Antineoplastic Agents; D007376:Interleukin-2; D010936:Plant Extracts; D011134:Polysaccharides; D043823:Taxoids; D014409:Tumor Necrosis Factor-alpha; D014866:Waste Products; D000077143:Docetaxel