2005
DOI: 10.1007/s00280-005-0016-5 View full text |Buy / Rent full text
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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… Show more

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“…4-methylumbelliferone (4-MU), a hyaluronan synthase inhibitor, has been shown to increase the efficiency of chemotherapy. 31 We reasoned that hyaluronan may play a role in masking of cell surface ErbB2. 32 We and ErbB2 in JIMT-1 and SKBR-3, respectively, show that these molecules are associated at the molecular level as well (Fig.1B), since FRET values above 5% are considered to imply significant association.…”
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“…4-methylumbelliferone (4-MU), a hyaluronan synthase inhibitor, has been shown to increase the efficiency of chemotherapy. 31 We reasoned that hyaluronan may play a role in masking of cell surface ErbB2. 32 We and ErbB2 in JIMT-1 and SKBR-3, respectively, show that these molecules are associated at the molecular level as well (Fig.1B), since FRET values above 5% are considered to imply significant association.…”
mentioning
“…Thus, we extended our studies that highlight the potential importance of the mechanism of constitutive HA-CD44 interaction antagonists that can suppress tumor growth by inhibiting HA-CD44v6-Cox-2 signaling axis, and other malignant properties as a therapeutic target for spontaneous tumors in Apc Min/ϩ mice. Because HA and CD44 are potential candidates for cancer treatment (13,71), in the present work we chose CD44 variants as prototype targets for the following reasons. 1) HA-CD44v6 interaction in cancer cells regulates activation of receptor tyrosine kinases that lead to cell survival and proliferation, and to COX-2 expression and function in colon cancer cells (30,31).…”
Section: Discussionmentioning
“…Nevertheless, at the concentrations used in cancer cells and tumor models and also the doses at which it is consumed as a dietary supplement, 4-MU is demonstrated to have antitumor activities. For example, in xenograft studies, oral administration of 4-MU has been shown to inhibit tumor growth and metastasis in prostate, B16 melanoma, skin, liver, osteosarcoma, breast, and esophageal cancer model systems (Bhattacharyya et al, 2009; Kudo et al, 2004; Lokeshwar et al, 2010; Nakazawa et al, 2006; Piccioni et al, 2012; Twarock et al, 2011; Urakawa, Nishida, Wasa, et al, 2012; Yoshihara et al, 2005). Recently, 4-MU was shown to inhibit bone metastasis in a breast cancer model (Hiraga et al, 2013).…”
Section: Targeting Ha Productionmentioning
“…Recently, 4-MU was shown to inhibit bone metastasis in a breast cancer model (Hiraga et al, 2013). As in the case of in vitro studies, some mouse xenograft studies have used 4-MU orally at doses as high as 1–3 g/kg; however, in other studies, 4-MU has shown remarkable efficacy at 200–400 mg/kg doses (Arai et al, 2011; Bhattacharyya et al, 2009; Hiraga et al, 2013; Kudo et al, 2004; Nakazawa et al, 2006; Okuda et al, 2012; Piccioni et al, 2012; Twarock et al, 2011; Urakawa, Nishida, Wasa, et al, 2012; Yoshihara et al, 2005). Based on the FDA’s formula of mouse-to-human dose conversion, 200–400 mg/kg doses in mice equates to 1.1–2.2 g/day doses in humans; these are doses at which 4-MU is consumed for improving liver health (Abate et al, 2001; Camarri & Marchettini, 1988; Garrett et al, 1993; Hoffmann et al, 2005; Quaranta et al, 1984; U.S.…”
Section: Targeting Ha Productionmentioning