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 .4.

  • Authors:
    • YS PARK
    • FQ RUAN
    • SI HAKOMORI
    • Y IGARASHI
  • View Affiliations

  • Published online on: September 1, 1995     https://doi.org/10.3892/ijo.7.3.487
  • Pages: 487-494
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

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, er 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.

Related Articles

Journal Cover

September 1995
Volume 7 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
PARK Y, RUAN F, HAKOMORI S and IGARASHI Y: 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 .4.. Int J Oncol 7: 487-494, 1995
APA
PARK, Y., RUAN, F., HAKOMORI, S., & IGARASHI, Y. (1995). 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 .4.. International Journal of Oncology, 7, 487-494. https://doi.org/10.3892/ijo.7.3.487
MLA
PARK, Y., RUAN, F., HAKOMORI, S., IGARASHI, Y."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 .4.". International Journal of Oncology 7.3 (1995): 487-494.
Chicago
PARK, Y., RUAN, F., HAKOMORI, S., IGARASHI, Y."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 .4.". International Journal of Oncology 7, no. 3 (1995): 487-494. https://doi.org/10.3892/ijo.7.3.487