An organ-specific alkaline phosphatase inhibitor, l-homoarginine, at 44.5 mm concentration inhibited [3H]thymidine uptake by C3H/He mouse osteosarcoma (OS) cells, while l-arginine, l-phenylalanine, and 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 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 glycine did not affect in vitro proliferation of OS cells. When the same number of viable OS cells was inoculated s.c. after culturing for 24 hr with 44.5 mm l-homoarginine or l-arginine, the tumor growth in mice given injections of l-homoarginine (but not l-arginine)-treated cells was delayed markedly. Electron microscopic studies indicated that the inhibiting effect on OS cell proliferation was associated with a marked increase in lysosomal granules and a decrease in virus-like structures. Similarly, biochemical assay for acid phosphatase of cell homogenates demonstrated a 2-fold increase of activity in l-homoarginine-treated cells when compared to controls and l-arginine-treated cells. Thus, l-homoarginine inhibits proliferation and alkaline phosphatase activity of mouse OS cells and appears to increase acid phosphatase activity and synthesis of lysosomal granules.
Supported by Grants CA 16699, CA 25965, and DE 02670 from NIH.