Anti-angiogenic effect of 5-Fluorouracil-based drugs against human colon cancer xenografts

Molecular Basis for the Induction of an Angiogenesis Inhibitor, Thrombospondin-1, by 5-Fluorouracil

“…Furthermore, our recent study showed that 5-FU-based drugs have antitumor function partially through up-regulation of TSP-1 in colorectal cancer xenografts (5). In accordance with these results, we also found that 5-FU enhanced the expression of TSP-1 in human colon cancer (KM12C and LOVO cells) and breast cancer MCF7 cells ( Fig.…”

“…Cancer Res 2008; 68: (17 5-FU-based drug, S-1, at sub-MTD concentration has antiangiogenic function through up-regulation of TSP-1 in colorectal cancer xenografts (5). To investigate possible mechanisms underlying the specificity of this effect, human colon cancer cells were treated with 5-FU at concentrations near or below IC 50 for 4 days ( Supplementary Fig.…”

“…Recently, we examined the antitumor and antiangiogenesis activities of the 5-FU-based drug, S-1 (1 mol/L teagaful, 0.4 mol/L 5-chloro-2,4-dihydroxypyridine, and 1mol/L potassium oxonate), at a sub-maximum tolerated dose (sub-MTD) on human colorectal cancer xenografts. The up-regulation of thrombospondin-1 (TSP-1), as well as down-regulation of microvessel formation, has been shown (5). However, the molecular basis for the suppression of angiogenesis by 5-FU has not been fully elucidated (6).…”

Metronomic chemotherapy regimens in oncology

“…В предклиниче-ских работах различные формы фторпиримидинов в метрономных дозах показывают свою активность в от-ношении аденокарцином молочной железы, толстой кишки, желудка, светлоклеточного рака поч ки, гепато-целлюлярного рака. Также изучается действие перо-ральных форм фторпиримидинов (UFT, капецитабин, S1) в низких дозировках [85][86][87][88]. Например, капецита-бин в метрономном режиме оказывает антиангиогенное действие в отношении опухолей толстой кишки, реали-зующееся через повышение экспрессии TSP-1 [87].…”

Capecitabine-induced stomatitis: a likely pathogenetic mechanism of oral lichenoid mucositis

“…Conversely, other studies have shown conflicting results about the role of the enzyme dihydropyrimidine dehydrogenase (DPD), with some showing that a high expression of DPD may enhance the production of 5-FU catabolites, with a subsequent increase of cell toxicity [10], and others showing that DPD activity has a negligible cytotoxic effect on human keratinocytes [11]. In addition, the damage to the upper corion vessels may be fostered indirectly through the inhibition of angiogenesis via the induction of thrombospondin-1 [12].…”