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Takao, S. et al.

Takao, Akiyama, Nakajo, Yoh, Kitazono, Natsugoe, Miyadera, Fukushima, Yamada, Aikou,

Suppression of metastasis by thymidine phosphorylase inhibitor.

We developed a novel inhibitor of thymidine phosphorylase ( TP), 5-chloro-6-[1-(2-iminopyrrolidinyl) methyl] uracil hydrochloride ( TPI), that is about 1000-fold more active than 6-amino-5-chlorouracil, one of the most potent TP inhibitors. TPI inhibited the high chemotactic motility and basement membrane invasion of KB/ TP cells, a TP-positive clone transfected with Rous sarcoma virus (RSV)/TP, to the levels seen in KB/CV cells, a control clone transfected with RSV. In nude mice, oral administration of TPI suppressed not only macroscopic liver metastases of highly metastatic KB/ TP cells but also the level of human beta-globin as a molecular marker of micrometastases in the livers of the mice. These findings demonstrate that TP plays a key role in the invasiveness and metastasis of TP- expressing solid tumors and suggest that TPI might be a novel antimetastatic agent for blood-borne metastasis.[1]

References

Suppression of metastasis by thymidine phosphorylase inhibitor. Takao, S., Akiyama, S.I., Nakajo, A., Yoh, H., Kitazono, M., Natsugoe, S., Miyadera, K., Fukushima, M., Yamada, Y., Aikou, T. Cancer Res. (2000) [Pubmed]

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