Abstract
Hyaluronan (HA) is a ubiquitous, major component of the pericellular matrix and is necessary for various physiological processes. It plays a very important role in biological barriers. We previously reported that 4-methylumbelliferone (MU) inhibits HA synthesis and pericellular HA matrix formation in cultured human skin fibroblasts, Streptococcus equi FM100, and B16F10 melanoma cells. We hypothesized that MU-mediated inhibition of HA synthesis and pericellular HA matrix formation would increase the efficacy of anticancer drugs. We have already demonstrated in vitro, using a sandwich binding protein assay and a particle exclusion assay, that MU inhibits HA synthesis and formation of the pericellular HA matrix, respectively, in human KP1-NL pancreatic cancer cells. AlamarBlue assay revealed that the anticancer effect of gemcitabine in KP1-NL cells was increased by pretreatment with MU. In vivo simultaneous administration of MU and gemcitabine to tumor-bearing mice with severe combined immunodeficiency disease (SCID) decreased the size of the primary and metastatic tumors more than did gemcitabine alone. These data strongly suggest that a combination of MU and gemcitabine is effective against human pancreatic cancer cells. MU may have potential as a chemosensitizer and may provide us with a new anticancer strategy.
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Abbreviations
- HA:
-
Hyaluronan
- HAS:
-
Hyaluronan synthase
- MU:
-
4-methylumbelliferone
- SCID:
-
Severe combined immunodeficiency disease
- FCS:
-
Fetal calf serum
- DMSO:
-
Dimethyl sulfoxide
- PBS:
-
Phosphate-buffered saline
- UGT:
-
UDP-glucuronyltransferase
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Nakazawa, H., Yoshihara, S., Kudo, D. et al. 4-methylumbelliferone, a hyaluronan synthase suppressor, enhances the anticancer activity of gemcitabine in human pancreatic cancer cells. Cancer Chemother Pharmacol 57, 165–170 (2006). https://doi.org/10.1007/s00280-005-0016-5
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DOI: https://doi.org/10.1007/s00280-005-0016-5