ABSTRACT
Phenanthroindolizidine alkaloids are a family of plant-derived compounds with significant antineoplastic activity as well as other effects like antiamebicidal, antiviral, and anti-inflammatory activities. The specific biomolecular targets of these compounds have not yet been clearly identified. S-(+)-Deoxytylophorinidine (CAT) is a new phenanthroindolizidine alkaloid, originally extracted from the roots of Tylophora atrofolliculata and Tylophora ovata. Potent anticancer activity was observed in vitro and in vivo. Neurotoxicity of CAT was also studied and it was far less serious than that of vinblastine. Interactions between this compound and DNA had been studied in detail in our laboratory previously, and we further studied its interactions with RNA.
Subject(s)
Alkaloids/isolation & purification , Alkaloids/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Indolizines/isolation & purification , Indolizines/pharmacology , Nucleic Acids/metabolism , Phenanthrolines/isolation & purification , Phenanthrolines/pharmacology , Tylophora/chemistry , Alkaloids/chemistry , Animals , Antineoplastic Agents, Phytogenic/chemistry , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Indolizines/chemistry , Mice , Neurotoxicity Syndromes/pathology , Nucleic Acids/drug effects , PC12 Cells , Phenanthrenes , Phenanthrolines/chemistry , Plant Roots/chemistry , Rats , Transplantation, Heterologous , Vinblastine/pharmacologyABSTRACT
LMPAB is a linear beta-(1-3)-glucan we isolated from polysaccharide extract of Agaricus blazei Murill (AbM). Effects of LMPAB on splenic natural killer (NK) cell activity, splenocyte proliferation, index of spleen and thymus, IFN-gamma expression in spleen and the concentration of IL-12, IL-18 and TNF-alpha in serum of S180 ascitic tumor-bearing mice were detected. The results showed that intraperitoneal injection of LMPAB (100 mg x kg(-1) x d(-1)) significantly increased the thymus index. LMPAB augmented splenic NK cell activity in a dose-dependent manner (50-200 mg x kg(-1) x d(-1)). The concanavalin A (3 microg/ ml) stimulated splenocyte proliferation was significantly enhanced by LMPAB at dosages of 50, 100 or 200 mg x kg(-1) x d(-1). Further studies showed that LMPAB (50, 100 or 200 mg x kg(-1) x d(-1), 14d) significantly increased the production of IL-12, TNF-alpha, IL-18 and the expression IFN-gamma as determined by ELISA and immunohistochemistry, respectively. These results clearly indicate that the anti-tumor effects of LMPAB are closely associated with up-regulation of activity of NK cells, expression of IFN-gamma in spleen and the systemic level of IL-12, IL-18 and TNF-alpha in tumor-bearing mice.
Subject(s)
Adjuvants, Immunologic/pharmacology , Agaricus/chemistry , Polysaccharides/pharmacology , Sarcoma 180/drug therapy , Animals , Cell Proliferation/drug effects , Coloring Agents , Cytokines/biosynthesis , Female , Immunity, Cellular/drug effects , Immunohistochemistry , Indicators and Reagents , Interferon-gamma/biosynthesis , Interferon-gamma/genetics , Interleukin-12/biosynthesis , Interleukin-18/biosynthesis , Killer Cells, Natural/drug effects , Killer Cells, Natural/immunology , Male , Mice , Mice, Inbred BALB C , Molecular Weight , Polysaccharides/chemistry , Polysaccharides/isolation & purification , Sarcoma 180/pathology , Spleen/cytology , Spleen/drug effects , Tetrazolium Salts , Thiazoles , Thymus Gland/cytology , Thymus Gland/drug effects , Tumor Necrosis Factor-alpha/biosynthesisABSTRACT
This study is to investigate the effect of Icogenin on and its mechanism in anti-metastasis of pancreatic cancer BxPC3 cells in vitro. Using transwell assay, the effects of Icogenin on the invasion of BxPC3 cells were measured. The abilities of cell motility and adhesion in BxPC3 cells were detected by MTT assay and wound healing assay, respectively. The MAPK signal pathway protein expressions were analyzed with Western blotting. Also, the activity of MMP2 was observed by zymography assay. Icogenin inhibited the abilities of motility, adhesion and invasion of pancreatic cancer BxPC3 cells in vitro (P < 0.05), in a dose-depended manner, and inhibited the secretion of MMP2 and phosphorylation of ERK. PD98059 and U0126 which were ERK inhibitors could suppress the abilities of invasion and metastasis of pancreatic cancer BxPC3 cells. It is concluded that Icogenin can inhibit the abilities of invasion and metastasis of pancreatic cancer in vitro by inhibiting the secretion of MMP2 and phosphorylation of ERK.
