Novel treatment of human pancreatic cancer xenografts with mimosine, a cell cycle regulator amino acid

Background: In recent years, several cell cycle checkpoint regulators, as potential anticancer drugs, are being evaluated, and some of these compounds are also tested in Phase I – II clinical trials. Among the cell synchronizing agents, mimosine, a plant-derived amino acid is known to block the cell cycle in late G1 phase. Based on encouraging in vitro studies we have treated human pancreatic cancer xenografts with mimosine.

Materials and Methods: Human ductal pancreatic carcinoma xenografts (PZX-40/8) growing in immunosuppressed mice have been treated with 30mg/kg b.w. L-mimosine subcutaneously for 34 days. Mimosine was administered daily, 6 times a week. Control animals were given 0.9% NaCl alone. In the paraffin-embedded tumors the proliferative and mitotic activities were checked by using immunohistochemical and flow cytometric methods.

Results: All the animals survived the experiment, and no specific toxic effects were noted. The treatment resulted in a retardation of the tumor growth (+220% vs. +288% in controls, P<0.04), the proliferative activity has decreased (Ki-67 score 22.6% vs. 29.9% in controls, P<0.007), and the apoptotic activity has highly significantly increased (14.5 +/1.1 apoptotic cells per mm2 vs. 3.8 +/0.4 apoptosis per mm2 in controls, P<0.0001). Flow cytometry has revealed a significant accumulation of the tumor cells in G1 phase (89.5±0.79% vs. 85.8±0.35% in controls, P<0.001). There was no statistically significant difference between the mitotic counts in the two groups.

Conclusions: The results suggest first time that the human pancreatic cancer can successfully be influenced by cell cycle regulators not only in vitro, but also in vivo system, and mimosine can be regarded as a potential antineoplastic compound.

This work was financially supported by the National Scientific Research Fund (OTKA T 34899).