Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the effect of Tiazofurin (TR-2-beta-D-furanosylthiazole-4-carbamide) on tumour cell invasion using metastatic 3LL-HH murine lung carcinoma and HT168-M1 human melanoma as experimental models. TR pretreatment of 3LL-HH cells, in a dose range of 15-60 microM, caused inhibition of cell proliferation, adhesion to plastic and extracellular matrix proteins. The TR-induced altered matrix interactions of 3LL-HH cells were reflected in decreased migration through matrix-covered filters. Analysis of the expression of certain invasion markers indicated that TR suppressed the expression of alpha v beta 3 integrin and MMP2 metalloproteinase. Biochemical studies indicated that 24 h 60 microM TR treatment of 3LL-HH cells inhibited glycosylation of a wide range of glycoproteins with the most pronounced effect on proteoglycans. TR pretreatment of 3LL-HH tumour cells resulted in the loss of lung colonisation potential in vivo. Furthermore, in vivo TR treatment inhibited the formation of liver metastases of 3LL-HH murine carcinoma. TR treatment also induced inhibition of integrin and MMP2 expression, migration and liver colonisation of the human melanoma HT168-M1 cell line. Since the TR concentration which inhibited various cellular functions was much lower for cell adhesion and lung colonisation than for cell proliferation, we suggest that the predominant effect of TR is the inhibition of metastasis in these model systems. We also suggest that both the effect of TR on tumour cell proliferation and on extracellular matrix interaction contribute to its remarkable antimetastatic potential in vivo.
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PMID:The antimetabolite Tiazofurin (TR) inhibits glycoconjugate biosynthesis and invasiveness of tumour cells. 869 25

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.
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PMID:The antitumor effect of Tiazofurin (TR) consists of anti-proliferative and anti-invasive elements. 904 5