+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Cooperative inhibitory effect of N,N,N-trimethylsphingosine and sphingosine-1-phosphate, co-incorporated in liposomes, on B16 melanoma cell metastasis: Cell membrane signaling as a target in cancer therapy IV



Cooperative inhibitory effect of N,N,N-trimethylsphingosine and sphingosine-1-phosphate, co-incorporated in liposomes, on B16 melanoma cell metastasis: Cell membrane signaling as a target in cancer therapy IV



International Journal of Oncology 7(3): 487-494



Two N-methylated derivatives of sphingosine (Sph), N,N-dimethyl-Sph (DMS) and N,N,N-trimethyl-Sph (TMS), have been shown to stereospecifically inhibit activity of protein kinase C and other kinases essential for active proliferation of tumor cells, as well as for activation of platelets and endothelial cells (ECs). DMS and TMS thereby inhibit tumor growth in vivo, and TMS inhibits in vivo metastatic potential of B16 melanoma cells. When TMS was administered in liposomes, its drug efficacy was increased and its undesirable side-effects were greatly reduced (Park YS, et al, Cancer Res 54: 2213, 1994). Sph-1-P, long known as the initial catabolite of Sph metabolism, has aroused considerable interest recently because of its inhibitory effect on cell motility (Sadahira Y, et al, Proc Natl Acad Sci USA 89: 9686, 1992). We now report that liposomes containing both TMS and Sph-1-P, in comparison to liposomes containing TMS or Sph-1-P alone, exert a much stronger inhibitory effect on B16 melanoma cell metastasis. This is ascribable to their inhibitory effect on tumor cell invasiveness through motility inhibition, in conjunction with the previously-observed inhibitory effect of TMS on activation of platelets and ECs. Furthermore, the liposomal formulation resulted in prolonged circulation time of both TMS and Sph-1-P in blood, and consequent higher concentration of these compounds in tumor tissues.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 008388619

Download citation: RISBibTeXText

PMID: 21552864


Related references

Cell membrane signaling as target in cancer therapy ii. inhibitory effect of n n n trimethylsphingosine on metastatic potential of murine b16 melanoma cell line through blocking of tumor cell dependent platelet aggregation. Cancer Research 51(22): 6019-6024, 1991

Liposomal N,N,N-trimethylsphingosine (TMS) as an inhibitor of B16 melanoma cell growth and metastasis with reduced toxicity and enhanced drug efficacy compared to free TMS: cell membrane signaling as a target in cancer therapy III. Cancer Research 54(8): 2213-2217, 1994

Cell membrane signaling as target in cancer therapy: inhibitory effect of N,N-dimethyl and N,N,N-trimethyl sphingosine derivatives on in vitro and in vivo growth of human tumor cells in nude mice. Cancer Research 51(6): 1613-1618, 1991

Inhibitory effect effect of n n n trimethylsphingosine tms on metastatic potential of murine b16 melanoma cell line through blocking of tumor cell dependent platelet aggregation. FASEB Journal 6(4): A1358, 1992

Expansion of Sphingosine Kinase and Sphingosine-1-Phosphate Receptor Function in Normal and Cancer Cells: From Membrane Restructuring to Mediation of Estrogen Signaling and Stem Cell Programming. International Journal of Molecular Sciences 19(2):, 2018

Triple Negative Breast Cancer Depends on Sphingosine Kinase 1 (SphK1)/Sphingosine-1-Phosphate (S1P)/Sphingosine 1-Phosphate Receptor 3 (S1PR3)/Notch Signaling for Metastasis. Medical Science Monitor 24: 1912-1923, 2018

The sphingosine kinase-1/sphingosine-1-phosphate axis in cancer: Potential target for anticancer therapy. Pharmacology and Therapeutics 195: 85-99, 2019

When the sphingosine kinase 1/sphingosine 1-phosphate pathway meets hypoxia signaling: new targets for cancer therapy. Cancer Research 69(9): 3723-3726, 2009

Sphingosine-1-phosphate/sphingosine kinase 1-dependent lymph node metastasis in esophageal squamous cell carcinoma. Surgery Today 47(11): 1312-1320, 2017

Sphingosine 1-Phosphate Signaling as a Target in Hepatic Fibrosis Therapy. Frontiers in Pharmacology 8: 579, 2017

Chemical synthesis of D-erythro-sphingosine-1-phosphate, and its inhibitory effect on cell motility. Bioorganic & Medicinal Chemistry Letters. 2(9): 973-978, 1992

Inhibitory regulation of Rac activation, membrane ruffling, and cell migration by the G protein-coupled sphingosine-1-phosphate receptor EDG5 but not EDG1 or EDG3. Molecular and Cellular Biology 20(24): 9247-9261, 2000

Sphingosine kinase 2 prevents the nuclear translocation of sphingosine 1-phosphate receptor-2 and tyrosine 416 phosphorylated c-Src and increases estrogen receptor negative MDA-MB-231 breast cancer cell growth: The role of sphingosine 1-phosphate receptor-4. Cellular Signalling 26(5): 1040-1047, 2014

Significance of PI3K/AKT signaling pathway in metastasis of esophageal squamous cell carcinoma and its potential as a target for anti-metastasis therapy. Oncotarget 8(24): 38755-38766, 2017

Sphingosine-1-phosphate promotes ovarian cancer cell proliferation by disrupting Hippo signaling. Oncotarget 8(16): 27166-27176, 2017