Cancer metastasis accounts for the majority of cancer-related deaths. One of the most important strategies for cancer therapy is the control of cancer metastasis. The liver is the most common organ for the metastasis of cancers in the digestive system, and the prognosis for cases with liver metastasis is extremely poor.1-4) Chemotherapy with fluorouracil, irinotecan, and leucovorin has been introduced to improve the postoperative prognosis.5) While the chemotherapy drugs kill tumor cells, they also damage normal cells, causing severe side-effects such as gastrointestinal dysfunction and bone marrow toxicity. Therefore, a chemotherapy that is effective for the metastasis of cancers without any side-effects is required. Docosahexaenoic acid (DHA) is an w-3 polyunsaturated long-chain fatty acid (w-3 PUFAs), whose antitumoral actions have been widely demonstrated in epidemiological and experimental studies. 6) For example, the diets containing fish oil rich in DHA had inhibitory effects against colon tumorigenesis.7-10) Furthermore, it was reported that DHA inhibited the growth of various cancer cells by cytotoxicity of the lipid peroxidation 11) and by apoptotic cell death in vitro. 12)This research suggests that DHA could be an effective drug for cancer chemotherapy. In addition, the relationships between dietary DHA and tumorigenesis have been attracting much attention from many researchers in food and medical science. However, there are few studies on the therapeutic effects of DHA on the growth of tumor cells in vivo. In particular, the therapeutic effects on the mouse models of carcinoma by intravenous treatment of DHA in vivo have not yet been examined due to the poor solubility in water.On the other hand, we have produced hybrid liposomes (HL) which can be prepared by just the sonication of vesicular and micellar molecules in a buffer solution. 13,14) HL are free from any contamination with organic solvents and remain stable for longer periods. The physical properties of these liposomes such as size, membrane fluidity, phase transition temperature, and hydrophobicity can be controlled by changing the constituents and compositional ratios of the HL. In the course of our study for HL, the following interest- 23) In addition, we elucidated the remarkably inhibitory effects on the growth of human colon cancer (HCT116) cells along with apoptosis and differentiation by HL including DHA in vitro. 19) However, therapeutic effects of HL including DHA in vivo have not yet been examined.In this study, we investigated the therapeutic effects of DMPC/DHA hybrid liposomes composed of 50 mol% L-adimyristoylphosphatidylcholine (DMPC) and 50 mol% DHA on the hepatic metastasis mouse models of human colon carcinoma HCT116 cells in vivo. Furthermore, the therapeutic effects on the hepatic metastasis mouse models by intravenous treatment of DMPC/DHA were revealed on the basis of histological analysis of liver tissues. MATERIAL AND METHODSPreparation of DMPC/DHA DMPC/DHA were prepared by sonication of a mixture containing DMPC (N...
Novel hybrid liposomes (DMPC/DHA) composed of l-α-dimyristoylphosphatidylcholine and docosahexaenoic acid were produced. DMPC/DHA were smaller and more stable than pure DMPC liposomes. It is attractive that DMPC/DHA could remarkably inhibit the growth of human colon cancer HCT116 cells along with apoptosis and differentiation in vitro.
Accumulation of b amyloid (Ab) peptides to nerve cells should be associated with the onset of Alzheimer's disease (AD). We prepared hybrid liposomes (HL) composed of 90 mol% phospholipids having various charged head groups (cationic L-a-dimyristoyltrimethyl ammonium propane (DMTAP), anionic L-a-dimyristoylphosphatidylserine (DMPS) or zwitterionic L-a-dimyristoylphosphatidylcholine (DMPC)) and 10 mol% polyoxyethylene(23) dodecyl ether (C 12 (EO) 23 )), and investigated the inhibitory eŠects of HL on the accumulation of Ab 1 40 peptides into human neuroblastoma (SH-SY5Y) cells in vitro. It is noteworthy that remarkable inhibitory eŠects on the accumulation of Ab 1 40 peptides were observed for SH-SY5Y cells treated with anionic HL-DMPS, though the accumulation was not inhibited by cationic HL-DMTAP. On the other hand, the immediate fusion of HL-DMTAP into SH-SY5Y cells was conrmed using a confocal laser microscope. Interestingly, the speciˆc interactions between anionic HL-DMPS and Ab 1 40 peptides were observed using the thio‰avin T (ThT) assay. In addition, the cytotoxicity of Ab 1 42 peptides on the SH-SY5Y cells decreased after the treatment with HL-DMPS. These results suggest that anionic HL-DMPS could be used as a novel medicine for AD in the future.
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