In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 3228-3228
Abstract:
Purpose: The aim of this study is to evaluate the cytotoxicity and anti-metastatic effect of a phytosphingosine derivative, N,N,N-trimethylphytosphingosine.iodide (TMP-I), and to compare it with that of TMP-I liposome. Background: Sphingolipids are known for ortho-signaling and anti-adhesion features as well as intracellular signal messenger in cell differentiation, proliferation and apoptosis. Sphingosine and sphinganine, structural analogs of sphingolipids were recognized as negative modulator of transmembrane signaling through protein kinase C (PKC) that plays an important role in the cancer treatment. Among them, phytosphingosine has been known for antitumor and anti-invasive effect through phytosphingosine-induced apoptosis mechanism. Recently it has been reported that N-monomethylphytosphingosine and N,N-dimethylphytosphingosine induced apoptosis via mitochondria-involved apoptosis such as caspase-8, caspase-3 and caspase-9 and this prompt us for this study. Methods: TMP-I solution was evaluated for cytotoxicity in various cancer cell lines and hemolysis in rat blood cells at various concentrations. The prepared TMP-I liposomes (DPPC:Chol:TMP-I at 5:5:1 mole ratio) were characterized by particle size and studied for in vitro cytotoxicity, cell migration and in vivo angiogenesis in rats. Furthermore, to evaluate the anti-metastatic effect of TMP-I liposomes, C57BL6 mice (n=5) were inoculated with B16F10 cells in tail vein for direct metastasis and footpad for spontaneous metastasis studies. Results: The prepared TMP-I liposomes were with a mean size of 150 nm. TMP-I solution showed significantly higher cytotoxicity and hemolysis (≥100 μg/ml) compared to that of TMP-I liposomes in several cancer cell lines. TMP-I liposomes showed significantly low cell migration and angiogenesis compared to control formulations. The in vivo study in mice showed that the numbers of lung nodules in the mice treated with TMP-I liposomes were significantly lower compared to that of control formulations. Conclusion: Our results suggested that the TMP-I liposome could be used as a potential carrier for the treatment of tumor metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3228. doi:10.1158/1538-7445.AM2011-3228
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2011-3228
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2011
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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