title: Novel microemulsion of tanshinone IIA, isolated from Salvia miltiorrhiza Bunge, exerts anticancer activity through inducing apoptosis in hepatoma cells.
abstract: Natural product Tanshinone IIA (TanIIA) induces apoptosis and differentiation in hepatocellular carcinoma (HCC) cells, but its clinical use is limited due to poor water solubility and lack of appropriate formulations for drug delivery. In this study, we capsulated TanIIA into a microemulsion (ME) that was composed of phospholipid, ethyl oleate, glycerol and pluronic F68. We then determined the anticancer effects and mechanisms of action for TanIIA ME with in vitro and in vivo HCC models. The mRNA and protein levels of apoptosis-related molecules (Bcl-2, Bax and caspase-3) were analyzed in murine hepatoma H22 cells and H22 tumor-bearing mice by flow cytometry, RT-PCR and immunofluorescence staining. Compared with the groups treated with empty ME and drug solution, the mRNA levels of Bax and caspase-3 were up-regulated, and the mRNA and protein levels of Bcl-2 were down-regulated in H22 cells treated with TanIIA ME in a dose-dependent manner. The mRNA and protein levels of Bax and caspase-3 were up-regulated and the Bcl-2 levels were also down-regulated in animals treated with TanIIA ME in a dose-dependent manner. Our results suggest that as a novel drug delivery system, microemulsion enhances the antitumor effects of TanIIA.
authors: Department of Pharmacy, The Second Affiliated Hospital of Dalian Medical University, Dalian 116027,  China.
authors: Hui
authors: H
authors: Ma
authors: Qing
authors: Q
authors: Fan
authors: Jia
authors: J
authors: Yu
authors: Jile
authors: J
authors: Xin
authors: Ce
authors: C
authors: Zhang
mesh_terms: D045784:Abietanes / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D004195:Disease Models, Animal; D004655:Emulsions; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D027561:Salvia miltiorrhiza; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic; C494827:Bax protein, mouse; D004655:Emulsions; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; C021751:tanshinone