Background:

L-Canavanine sulfate is a selective inhibitor of inducible NO synthase.

L-Canavanine sulfate (L-CAV) causes only a limited degree of cytotoxicity in HeLa, Hep G2, and SK-HEP-1 cells when given alone in arginine-rich media with IC50 values ranging from 5 to 10 mM. In HaCaT keratinocyte cell line, IC50 of L-Canavanine sulfate exceeds the concentration of 10 mM, indicating low cytotoxicity in normal cells in vitro. In arginine-free media, IC50 of L-Canavanine sulfate in HeLa, Hep G2, and SK-HEP-1 cells are 0.21±0.04; 0.64±0.16; and 1.18±0.14 mM, respectively. L-Canavanine sulfate, which is hardly toxic alone, potentiates the cytotoxicity of vinblastine (VIN) and paclitaxel (PTX) in HeLa and hepatocellular carcinoma cells[2].

Administration of L-Canavanine sulfate (100 mg/kg) produces a moderate increase in mean arterial pressure of 20 mm Hg, returns blood pressure to near basal levels and completely attenuates the lipopolysaccharide-induced hypotension. All, but one, endotoxaemic rats dosed with L-Canavanine sulfate (100 mg/kg) survive for 6 h post lipopolysaccharide, after which time the experiment is terminated (n=7)[1]. L-canavanine inhibits DNA synthesis by Li 210 cells in vivo and significantly increases the lifespan of animals bearing the Li 210 leukemia. An optimal dose of 18 g/kg produces a peak increase in lifespan of 44%. The therapeutic dose range is narrow, and a dose of 24 g/kg causes death due to drug toxicity[3].

参考文献:
[1]. Teale DM, et al. L-canavanine restores blood pressure in a rat model of endotoxic shock. Eur J Pharmacol. 1994 Dec 12;271(1):87-92.
[2]. Nurcahyanti AD, et al. Cytotoxic potentiation of vinblastine and paclitaxel by L-canavanine in human cervical cancer and hepatocellular carcinoma cells. Phytomedicine. 2015 Dec 15;22(14):1232-7.
[3]. Green MH, et al. Antitumor activity of L-canavanine against L1210 murine leukemia. Cancer Res. 1980 Mar;40(3):535-7.