Therapeutic Effects of Cationic Hybrid Liposomes on the Hepatic Metastasis of Colon Carcinoma Along with Apoptosis <i>in Vivo</i>

Abstract

Therapeutic effects of cationic hybrid liposomes (HL) composed of 87 mol% dimyristoyl-phosphatidylcholine (DMPC), 5 mol% polyoxyethylene (21) dodecyl ether (C 12 (EO) 21 ) and 8 mol% O,O′-ditetradecanoyl-N-(α-trimethyl-ammonioacetyl) diethanolamine chloride (2C 14 ECl) on the metastasis of human colon carcinoma (HCT116) cells were examined in vivo. Cationic HL having a hydrodynamic diameter less than 150 nm were preserved for one month. Therapeutic effects were obtained in the hepatic metastasis mouse models of HCT116 cells after the intravenous injection of cationic HL. The histological analysis indicated the induction of apoptosis in the liver section of the hepatic metastasis mouse models treated with cationic HL in vivo. Therapeutic effects of cationic HL without any drugs on the hepatic metastasis were revealed for the first time on the basis of histological analyses in vivo.Key words hybrid liposome; hepetic metastasis; colon carcinoma; apoptosis; chemotherapy Colorectal cancer (CRC) is the third most common cancer in the world with more than 600000 deaths every year. 1)About 40% of patients with CRC develop metastases. Because the venous drainage of the colon is through the portal vein, which goes directly to the liver, more than 70% of the CRC metastases are located in the hepatic tissue. Metastatic diffusion results in a very poor prognosis with a median survival of about two years in treated patients. However, long term survival is possible in the 15% of patients that can benefit of hepatic metastasis surgery, usually after induction chemotherapy.2) Induction chemotherapy is a first-line treatment for cancer in which a patient is given doses of chemotherapy first. These doses may be high, with the goal of attempting to quickly attack the cancer, and after induction chemotherapy, additional treatment options such as surgical resection can be selected.3) 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, chemotherapy that is effective for the metastasis of cancers without any side-effects is required.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. 4,5) 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 interesting results have been obtained. (a) Stereochemical control of the enantioselective hydrolysis of amino acid esters could be established by temperature regulation and changing the composition of the HL. 14) However, therapeutic effects of cationic HL in vivo have not yet been examined.In this study, we investigated the therapeutic effects of three-component cationic ...

Polyunsaturated Fatty Acids and Their Derivatives: Therapeutic Value for Inflammatory, Functional Gastrointestinal Disorders, and Colorectal Cancer

“…This inhibits liver metastasis and leads to decrease in the tumor volume. Importantly, hybrid liposomes (HLs) including PUFAs have demonstrated an inhibitory effect on the growth of tumor cells both in vitro and in vivo (Ichihara et al, 2014). Tanaka et al (2008) demonstrated that HLs enriched with n-3, n-6, and n-9 PUFAs inhibit the growth of tumor cells, including colon tumor (WiDr) cells in vitro .…”

“…They were then randomized for intravenous administration of liposomes, containing either L-α-dimyristoylphosphatidylcholine (DMPC) (136 mg/kg/d) or 50% molar DHA (65.7 mg/kg/d) and 50% molar DMPC. After 14 days of therapy, a significant improvement in median survival time and induction of apoptosis in liver metastases were observed (Ichihara et al, 2014). …”

Cell Cycle Arrest by Hybrid Liposomes for Human Lung Carcinoma Cells

“…HL, composed of L-α-dimyristoylphosphatidylcholine (DMPC) and polyoxyethylene (23) dodecyl ethers (C 12 (EO) 23 ), are effective for inhibiting the growth of various cancer cells in vitro [6][7][8][9], in vivo [10,11] and clinical applications [12]. Recently, we have reported that HL composed of 90 mol% DMPC and 10 mol% C 12 (EO) 23 induced apoptosis in various cancer cells including NSCLC (A549, H460, H23 and H520) cells [9,[13][14][15].…”