The antitumor effect of Tiazofurin (TR) consists of anti-proliferative and anti-invasive elements.
We have studied the effects of the antimetabolite, Tiazofurin (TR-2-beta-D-furanosylthiazole-4-carboxamide), on the metastatization of HT168-M1 human melanoma cell line compared to 3LL-HH murine lung carcinoma. TR pretreatment of 3LL-HH cells, in a dose range 15-60 microM, caused inhibition of cell proliferation as well as adhesion to the EHS-matrix. TR inhibited the entry of adherent tumor cells to the S phase and accumulation in G1, however in non-adherent cells TR completely inhibited the entry of tumor cells to G2 phase. In contrast to these data TR treatment of HT168-M1 cells did not cause inhibition of cell proliferation, a change in cell cycle distribution or in the quantity of apoptotic cells. However, TR pretreatment did inhibit the adhesion to and migration through EHS-matrix of melanoma cells similar to 3LL-HH cells. Furthermore, in vivo TR treatment inhibited the formation of liver metastases of HT168-M1 melanoma cells without major effects on the spleen primary tumor. Since in vivo TR treatment of HT168-M1 and 3LL-HH tumor bearing mice significantly decreased the number and incidence of liver metastases though there was a different effect on the in vitro/in vivo growth (lack of inhibitory effect in case of IIT168-M1 cells), we suggest that the antiproliferative and anti-metastatic effects of TR could be separated. We also suggest that the antimetastatic effects of TR are due to inhibition of adhesion and migration of tumor cells.
Tóvári
J
J
1st Institute of Pathology and Experimental Cancer Research, Semmelweis, University of Medicine, Budapest VIII, Hungary.
Bocsi
J
J
Ladányi
A
A
Lapis
K
K
Timár
J
J
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000556:secondary; D008175:Lung Neoplasms / Q000473:pathology; D008545:Melanoma / Q000473:pathology; D051379:Mice; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D012254:Ribavirin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D012254:Ribavirin; C033706:tiazofurin