Inhibitory effects of phaseolotoxin on proliferation of leukemia cells HL-60, K-562 and L1210 and pancreatic cells RIN-m5F

Abstract 

Phaseolotoxin (PT) is a non-host specific phytotoxin produced by the plant pathogenic bacterium Pseudomonas syringae (P.s.) pv. phaseolicola. In the present study, the inhibitory effect of PT on the proliferation of leukemia cells was studied. After 4 days of treatment, PT decreased cell growth of leukemia cell lines HL-60, K-562 and L1210 in a dose-dependent manner. In addition, PT also reduced cell growth of the insulinoma pancreatic cell line RIN-m5F. IC₅₀ values were 2.1±1.0μM (HL-60), 13.3±3.7μM (K-562), 2.5±0.4μM (L1210) and 5.5±0.3μM (RIN-m5F). Although the exact mechanism by which PT inhibits cell growth in these cells is currently not known, we present first evidence that PT may in part be active via inhibition of ornithine decarboxylase (ODC). Based on our findings, PT presents a lead compound with potential for further development into a new anti-cancer agent.

Abbreviations:  DFMO, α-dl-difluoromethylornithine, MTS, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, OCT, ornithine carbamoyltransferase, ODC, ornithine decarboxylase, P.s., Pseudomonas syringae, PT, phaseolotoxin

Keywords:  Anti-cancer agent, Ornithine decarboxylase, Phaseolotoxin, HL-60, K-562, L1210, RIN-m5F