[Inhibitory effect of L-homoarginine on murine osteosarcoma cell proliferation].
An organ-specific alkaline phosphatase (AIP) inhibitor, L-homoarginine at 44.5 mM concentration inhibited 3H-thymidine uptake by mouse C3H/He osteosarcoma (OS) cells, while L-arginine, L-phenylalanine and L-glycine had little effect on the uptake. This inhibitory effect by L-homoarginine persisted even after the cells were washed free of the amino acid with fresh media. L-homoarginine did not affect 3H-thymidine uptake by mouse myeloma MOPC 104E cells. In the long-term culture, 22.3 mM L-homoarginine inhibited proliferation of OS cells. L-Arginine at the same concentration inhibited the proliferation to a lesser extent. On the other hand, L-phenylalanine and L-glycine did not affect in vitro proliferation of OS cells. When similar numbers of viable OS cells were inoculated s. c. after culturing with 44.5 mM L-homoarginine or L-arginine for 24 hr, the tumor growth in mice injected with L-homoarginine (but not L-arginine) treated cells was delayed markedly. Electron microscopic studies indicated that the inhibitory effect on OS cell proliferation was associated with a marked increase in lysosomal granules and a decrease in virus-like structures. Similarly, a biochemical assay of acid phosphatase (AcP) of the cell homogenates demonstrated two-fold increase of the activity in L-homoarginine treated cells when compared to the controls and L-arginine treated cells. Thus, L-homoarginine inhibits proliferation and AIP activity of mouse OS cells and appears to promote cell differentiation as evidenced by the increased synthesis of cytoplasmic granules and acid phosphatase activity.
D000469:Alkaline Phosphatase / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives*; D002478:Cells, Cultured; D005260:Female; D006709:Homoarginine / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D009113:Muramidase / Q000096:biosynthesis; D012516:Osteosarcoma / Q000201:enzymology / Q000473:pathology*; D012513:Sarcoma, Experimental / Q000473:pathology; D013237:Stereoisomerism
D000596:Amino Acids; D006709:Homoarginine; D001120:Arginine; D000469:Alkaline Phosphatase; D009113:Muramidase