title: The antitumour activities induced by pegylated liposomal cytochalasin D in murine models.
abstract: Cytochalasin D targets actin and is ubiquitous in eukaryotic cells. When cytochalasin D is used as a cytotoxic agent in cancer therapy, it causes significant side effects. To prevent this, cytochalasin D can be encapsulated in polyethylene liposomes. In this study, high-performance liquid chromatography observation of the biodistribution of pegylated liposomal cytochalasin D in tumour-bearing mice showed that liposomal cytochalasin D could be conveniently dissolved in water for i.v. injection and that it specifically accumulated in tumour tissues, more than natural cytochalasin D did. The half-time of liposomal cytochalasin D in the plasma was also significantly longer than that of natural cytochalasin D (4h versus 10 min). MTT 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that liposomal cytochalasin D treatment could cause significant inhibition of cell proliferation in vitro in a manner similar to that of natural cytochalasin D. The antitumour activities of liposomal cytochalasin D were investigated in B16 melanoma, CT26 colorectal carcinoma and H22 hepatoma models, and the results indicated that liposomal cytochalasin D could significantly inhibit tumour growth and prolong survival in a manner similar to that of cisplatin. TUNEL-based apoptosis assays showed that liposomal cytochalasin D induced significant tumour cell apoptosis. Significant inhibition of tumour angiogenesis was observed in mice treated with liposomal cytochalasin D. In addition, no significant side effects were observed in mice treated with liposomal cytochalasin D. Our results show that liposomal cytochalasin D increases solubility and bioavailability, a lower incidence of side effects and improves antitumour effects, indicating its potential as a chemical agent for cancer therapy.
authors.affiliation: Hainan Provincial Key Laboratory of Tropical Medicine, Hainan Medical College, Haikou, People's Republic of China.
authors.forename: Feng-ying
authors.initials: FY
authors.lastname: Huang
authors.forename: Wen-li
authors.initials: WL
authors.lastname: Mei
authors.forename: Yue-nan
authors.initials: YN
authors.lastname: Li
authors.forename: Guang-hong
authors.initials: GH
authors.lastname: Tan
authors.forename: Hao-fu
authors.initials: HF
authors.lastname: Dai
authors.forename: Jun-li
authors.initials: JL
authors.lastname: Guo
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Yong-hao
authors.initials: YH
authors.lastname: Huang
authors.forename: Huan-ge
authors.initials: HG
authors.lastname: Zhao
authors.forename: Song-lin
authors.initials: SL
authors.lastname: Zhou
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Ying-ying
authors.initials: YY
authors.lastname: Lin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D001682:Biological Availability; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015638:Cytochalasin D / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D007275:Injections, Intravenous; D008081:Liposomes; D008114:Liver Neoplasms, Experimental / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008546:Melanoma, Experimental / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D012995:Solubility; D014018:Tissue Distribution; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D015638:Cytochalasin D; D011092:Polyethylene Glycols