The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Keiichi Takagaki - One of the best experts on this subject based on the ideXlab platform.
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study of hyaluronan synthase inhibitor 4 methylumbelliferone derivatives on human pancreatic cancer cell kp1 nl
Biochemical and Biophysical Research Communications, 2006Co-Authors: Hajime Morohashi, Atsushi Kon, Shuichi Yoshihara, Ikuko Kakizaki, Mutsuo Sasaki, Makoto Nakai, Masanori Yamaguchi, Keiichi TakagakiAbstract:The structure of 4-Methylumbelliferone (MU) consists of coumarin with 4-methyl group and 7-hydroxy group. MU inhibits HA synthesis and pericellular HA matrix formation. In this study, we used 10 MU derivatives which have hydroxy groups and methyl groups at various positions of coumarin to investigate a more effective HA inhibitor than MU. First, human pancreatic cancer cell (KP1-NL) growth assay was analyzed by Alamar Blue to determine the non-toxic concentration of MU derivatives, and the inhibitory effect on HA synthesis in the cell cultures was analyzed by HA measuring kit. Next, cell surfaces of cancer cells were analyzed by particle-exclusion assay. In conclusion, both hydroxy and methyl groups are necessary for HA inhibition by MU, and two hydroxy groups inhibited HA synthesis more strongly than MU.
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4-Methylumbelliferone, a hyaluronan synthase suppressor, enhances the anticancer activity of gemcitabine in human pancreatic cancer cells
Cancer Chemotherapy and Pharmacology, 2006Co-Authors: Hideaki Nakazawa, Keiichi Takagaki, Atsushi Kon, Shuichi Yoshihara, Daisuke Kudo, Ikuko Kakizaki, Hajime Morohashi, Mutsuo SasakiAbstract: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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a hyaluronan synthase suppressor 4 methylumbelliferone inhibits liver metastasis of melanoma cells
FEBS Letters, 2005Co-Authors: Shuichi Yoshihara, Masahiko Endo, Atsushi Kon, Daisuke Kudo, Hideaki Nakazawa, Ikuko Kakizaki, Mutsuo Sasaki, Keiichi TakagakiAbstract:4-Methylumbelliferone (MU) inhibits the cell surface hyaluronan (HA) formation, and that such inhibition results in suppression of adhesion and locomotion of cultured melanoma cells. Here, we examine the effect of MU on melanoma cell metastasis in vivo. MU-treated melanoma cells showed both decreased cell surface HA formation and suppression of liver metastasis after injection into the mice. Oral administration of MU to mice decreased tissue HA content. These HA knock-down mice displayed suppressed liver metastasis. Thus, both cell surface HA of melanoma cells and recipient liver HA can promote liver metastasis, indicating that MU has potential as an anti-metastatic agent.
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effect of a hyaluronan synthase suppressor 4 methylumbelliferone on b16f 10 melanoma cell adhesion and locomotion
Biochemical and Biophysical Research Communications, 2004Co-Authors: Daisuke Kudo, Masahiko Endo, Atsushi Kon, Shuichi Yoshihara, Ikuko Kakizaki, Mutsuo Sasaki, Keiichi TakagakiAbstract:Hyaluronan (HA) is a ubiquitous, major component of the extracellular matrix. It is involved in cell adhesion and locomotion, and hence in tumor metastasis. We have previously reported that 4-Methylumbelliferone (MU) inhibits HA synthesis and may be a useful tool for examining the functions of HA. We here demonstrate that the formation of cell surface HA by melanoma cells and its release into the culture medium are inhibited by MU. Adhesion and locomotion assays revealed that the adhesion and locomotion of melanoma cells were dose-dependently inhibited by MU. Conversely, treatment with exogenous HA enhanced both adhesion and locomotion. Thus, preventing the formation of cell surface HA reduced both the adhesion and locomotion of melanoma cells, suggesting that MU may act as an inhibitor of tumor metastasis.
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hyaluronic acid deficient extracellular matrix induced by addition of 4 methylumbelliferone to the medium of cultured human skin fibroblasts
Biochemical and Biophysical Research Communications, 1995Co-Authors: Toshiya Nakamura, Keiichi Takagaki, Kanji Tanaka, Shigeru Shibata, Tsuyoshi Higuchi, Masahiko EndoAbstract:Abstract The effects of xylosyl-β-D-(4-Methylumbelliferone) and its aglycone, 4-Methylumbelliferone, on hyaluronic acid synthesis were investigated in cultured human skin fibroblasts. Xylosyl-β-D-(4-Methylumbelliferone) added to the medium of cultured cell reduced the synthesis of hyaluronic acid. Furthermore, 4-Methylumbelliferone reduced the production of hyaluronic acid markedly. In addition, 4-Methylumbelliferone had hardly any effect on proteoglycan synthesis, whereas xylosyl-β-D-(4-Methylumbelliferone) produced a large amount of glycosaminoglycan chains. The present results indicate that cells cultured with 4-Methylumbelliferone produce a hyaluronic-acid-deficient extracellular matrix, which will be useful for functional studies of hyaluronic acid.
Masahiko Endo - One of the best experts on this subject based on the ideXlab platform.
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a hyaluronan synthase suppressor 4 methylumbelliferone inhibits liver metastasis of melanoma cells
FEBS Letters, 2005Co-Authors: Shuichi Yoshihara, Masahiko Endo, Atsushi Kon, Daisuke Kudo, Hideaki Nakazawa, Ikuko Kakizaki, Mutsuo Sasaki, Keiichi TakagakiAbstract:4-Methylumbelliferone (MU) inhibits the cell surface hyaluronan (HA) formation, and that such inhibition results in suppression of adhesion and locomotion of cultured melanoma cells. Here, we examine the effect of MU on melanoma cell metastasis in vivo. MU-treated melanoma cells showed both decreased cell surface HA formation and suppression of liver metastasis after injection into the mice. Oral administration of MU to mice decreased tissue HA content. These HA knock-down mice displayed suppressed liver metastasis. Thus, both cell surface HA of melanoma cells and recipient liver HA can promote liver metastasis, indicating that MU has potential as an anti-metastatic agent.
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effect of a hyaluronan synthase suppressor 4 methylumbelliferone on b16f 10 melanoma cell adhesion and locomotion
Biochemical and Biophysical Research Communications, 2004Co-Authors: Daisuke Kudo, Masahiko Endo, Atsushi Kon, Shuichi Yoshihara, Ikuko Kakizaki, Mutsuo Sasaki, Keiichi TakagakiAbstract:Hyaluronan (HA) is a ubiquitous, major component of the extracellular matrix. It is involved in cell adhesion and locomotion, and hence in tumor metastasis. We have previously reported that 4-Methylumbelliferone (MU) inhibits HA synthesis and may be a useful tool for examining the functions of HA. We here demonstrate that the formation of cell surface HA by melanoma cells and its release into the culture medium are inhibited by MU. Adhesion and locomotion assays revealed that the adhesion and locomotion of melanoma cells were dose-dependently inhibited by MU. Conversely, treatment with exogenous HA enhanced both adhesion and locomotion. Thus, preventing the formation of cell surface HA reduced both the adhesion and locomotion of melanoma cells, suggesting that MU may act as an inhibitor of tumor metastasis.
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hyaluronic acid deficient extracellular matrix induced by addition of 4 methylumbelliferone to the medium of cultured human skin fibroblasts
Biochemical and Biophysical Research Communications, 1995Co-Authors: Toshiya Nakamura, Keiichi Takagaki, Kanji Tanaka, Shigeru Shibata, Tsuyoshi Higuchi, Masahiko EndoAbstract:Abstract The effects of xylosyl-β-D-(4-Methylumbelliferone) and its aglycone, 4-Methylumbelliferone, on hyaluronic acid synthesis were investigated in cultured human skin fibroblasts. Xylosyl-β-D-(4-Methylumbelliferone) added to the medium of cultured cell reduced the synthesis of hyaluronic acid. Furthermore, 4-Methylumbelliferone reduced the production of hyaluronic acid markedly. In addition, 4-Methylumbelliferone had hardly any effect on proteoglycan synthesis, whereas xylosyl-β-D-(4-Methylumbelliferone) produced a large amount of glycosaminoglycan chains. The present results indicate that cells cultured with 4-Methylumbelliferone produce a hyaluronic-acid-deficient extracellular matrix, which will be useful for functional studies of hyaluronic acid.
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a novel oligosaccharide xylosyl beta 1 4xylosyl beta 1 4 methylumbelliferone synthesized by cultured human skin fibroblasts in the presence of 4 methylumbelliferyl beta d xyloside
Journal of Biochemistry, 1994Co-Authors: Jun Izumi, Keiichi Takagaki, Shigeru Shibata, Toshiya Nakamura, Kaoru Kojima, Ikunoshin Kato, Masahiko EndoAbstract:4-Methylumbelliferyl-beta-D-xyloside (Xyl-MU) was added to the medium of cultured human skin fibroblasts. After incubation, the culture medium was pooled, concentrated with a lyophilizer, and dialyzed against distilled water. Then the Xyl-MU derivatives in the diffusate were purified by gel-filtration and HPLC. A novel Xyl-MU derivative was obtained, in addition to the previously reported Xyl-MU derivatives, Xyl-MU-induced glycosaminoglycan (GAG-MU), SA-Gal-Xyl-MU, GlcA-Xyl-MU, Gal-Gal-Xyl-MU, and Gal-Xyl-MU. This Xyl-MU derivative was subjected to carbohydrate composition analysis, enzyme digestion, Smith degradation and ion-spray mass spectrometric analysis, and the results indicated that it was Xyl beta 1-4Xyl beta 1-MU. Although the quantity of Xyl beta 1-4Xyl beta 1-MU synthesized by human skin fibroblasts increased with incubation time, its production was independent of that of the GAG-MU. Xyl-Xyl-MU is different from the intermediates in the regular pathway of GAG-MU biosynthesis initiated by added Xyl-MU, posing an interesting question as to its significance in GAG biosynthesis.
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characterization of β d xyloside induced glycosaminoglycans and oligosaccharides in cultured human skin fibroblasts
Journal of Biochemistry, 1991Co-Authors: Keiichi Takagaki, Toshiya Nakamura, Atsushi Kon, Shinri Tamura, Masahiko EndoAbstract:Human skin fibroblasts were incubated in the presence of a fluorogenic xyloside, 4-methylumbelliferyl beta-D-xyloside. Three fluorogenic components were isolated and purified from the culture medium by gel permeation high-performance liquid chromatography. Their structures were then characterized by enzymatic digestion, fast-atom-bombardment mass spectrometry, gas-liquid chromatography, and electrophoresis on cellulose acetate membrane. The results showed that one of the components was a mixture of dermatan sulfate (70%) and chondroitin sulfate (30%), bearing the 4-Methylumbelliferone at the reducing termini, and having an average molecular weight of 9,200. The others had the structures galactosyl-galactosyl-xylosyl-4-Methylumbelliferone and galactosyl-xylosyl-4-Methylumbelliferone, respectively, representing the linkage region between the glycosaminoglycan chains and core protein, except that 4-Methylumbelliferone replaced the amino acid. Moreover, it was demonstrated that these oligosaccharides were intermediates of glycosaminoglycan synthesis, not depolymerized products.
Atsushi Kon - One of the best experts on this subject based on the ideXlab platform.
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study of hyaluronan synthase inhibitor 4 methylumbelliferone derivatives on human pancreatic cancer cell kp1 nl
Biochemical and Biophysical Research Communications, 2006Co-Authors: Hajime Morohashi, Atsushi Kon, Shuichi Yoshihara, Ikuko Kakizaki, Mutsuo Sasaki, Makoto Nakai, Masanori Yamaguchi, Keiichi TakagakiAbstract:The structure of 4-Methylumbelliferone (MU) consists of coumarin with 4-methyl group and 7-hydroxy group. MU inhibits HA synthesis and pericellular HA matrix formation. In this study, we used 10 MU derivatives which have hydroxy groups and methyl groups at various positions of coumarin to investigate a more effective HA inhibitor than MU. First, human pancreatic cancer cell (KP1-NL) growth assay was analyzed by Alamar Blue to determine the non-toxic concentration of MU derivatives, and the inhibitory effect on HA synthesis in the cell cultures was analyzed by HA measuring kit. Next, cell surfaces of cancer cells were analyzed by particle-exclusion assay. In conclusion, both hydroxy and methyl groups are necessary for HA inhibition by MU, and two hydroxy groups inhibited HA synthesis more strongly than MU.
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4-Methylumbelliferone, a hyaluronan synthase suppressor, enhances the anticancer activity of gemcitabine in human pancreatic cancer cells
Cancer Chemotherapy and Pharmacology, 2006Co-Authors: Hideaki Nakazawa, Keiichi Takagaki, Atsushi Kon, Shuichi Yoshihara, Daisuke Kudo, Ikuko Kakizaki, Hajime Morohashi, Mutsuo SasakiAbstract: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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a hyaluronan synthase suppressor 4 methylumbelliferone inhibits liver metastasis of melanoma cells
FEBS Letters, 2005Co-Authors: Shuichi Yoshihara, Masahiko Endo, Atsushi Kon, Daisuke Kudo, Hideaki Nakazawa, Ikuko Kakizaki, Mutsuo Sasaki, Keiichi TakagakiAbstract:4-Methylumbelliferone (MU) inhibits the cell surface hyaluronan (HA) formation, and that such inhibition results in suppression of adhesion and locomotion of cultured melanoma cells. Here, we examine the effect of MU on melanoma cell metastasis in vivo. MU-treated melanoma cells showed both decreased cell surface HA formation and suppression of liver metastasis after injection into the mice. Oral administration of MU to mice decreased tissue HA content. These HA knock-down mice displayed suppressed liver metastasis. Thus, both cell surface HA of melanoma cells and recipient liver HA can promote liver metastasis, indicating that MU has potential as an anti-metastatic agent.
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effect of a hyaluronan synthase suppressor 4 methylumbelliferone on b16f 10 melanoma cell adhesion and locomotion
Biochemical and Biophysical Research Communications, 2004Co-Authors: Daisuke Kudo, Masahiko Endo, Atsushi Kon, Shuichi Yoshihara, Ikuko Kakizaki, Mutsuo Sasaki, Keiichi TakagakiAbstract:Hyaluronan (HA) is a ubiquitous, major component of the extracellular matrix. It is involved in cell adhesion and locomotion, and hence in tumor metastasis. We have previously reported that 4-Methylumbelliferone (MU) inhibits HA synthesis and may be a useful tool for examining the functions of HA. We here demonstrate that the formation of cell surface HA by melanoma cells and its release into the culture medium are inhibited by MU. Adhesion and locomotion assays revealed that the adhesion and locomotion of melanoma cells were dose-dependently inhibited by MU. Conversely, treatment with exogenous HA enhanced both adhesion and locomotion. Thus, preventing the formation of cell surface HA reduced both the adhesion and locomotion of melanoma cells, suggesting that MU may act as an inhibitor of tumor metastasis.
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characterization of β d xyloside induced glycosaminoglycans and oligosaccharides in cultured human skin fibroblasts
Journal of Biochemistry, 1991Co-Authors: Keiichi Takagaki, Toshiya Nakamura, Atsushi Kon, Shinri Tamura, Masahiko EndoAbstract:Human skin fibroblasts were incubated in the presence of a fluorogenic xyloside, 4-methylumbelliferyl beta-D-xyloside. Three fluorogenic components were isolated and purified from the culture medium by gel permeation high-performance liquid chromatography. Their structures were then characterized by enzymatic digestion, fast-atom-bombardment mass spectrometry, gas-liquid chromatography, and electrophoresis on cellulose acetate membrane. The results showed that one of the components was a mixture of dermatan sulfate (70%) and chondroitin sulfate (30%), bearing the 4-Methylumbelliferone at the reducing termini, and having an average molecular weight of 9,200. The others had the structures galactosyl-galactosyl-xylosyl-4-Methylumbelliferone and galactosyl-xylosyl-4-Methylumbelliferone, respectively, representing the linkage region between the glycosaminoglycan chains and core protein, except that 4-Methylumbelliferone replaced the amino acid. Moreover, it was demonstrated that these oligosaccharides were intermediates of glycosaminoglycan synthesis, not depolymerized products.
Mutsuo Sasaki - One of the best experts on this subject based on the ideXlab platform.
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study of hyaluronan synthase inhibitor 4 methylumbelliferone derivatives on human pancreatic cancer cell kp1 nl
Biochemical and Biophysical Research Communications, 2006Co-Authors: Hajime Morohashi, Atsushi Kon, Shuichi Yoshihara, Ikuko Kakizaki, Mutsuo Sasaki, Makoto Nakai, Masanori Yamaguchi, Keiichi TakagakiAbstract:The structure of 4-Methylumbelliferone (MU) consists of coumarin with 4-methyl group and 7-hydroxy group. MU inhibits HA synthesis and pericellular HA matrix formation. In this study, we used 10 MU derivatives which have hydroxy groups and methyl groups at various positions of coumarin to investigate a more effective HA inhibitor than MU. First, human pancreatic cancer cell (KP1-NL) growth assay was analyzed by Alamar Blue to determine the non-toxic concentration of MU derivatives, and the inhibitory effect on HA synthesis in the cell cultures was analyzed by HA measuring kit. Next, cell surfaces of cancer cells were analyzed by particle-exclusion assay. In conclusion, both hydroxy and methyl groups are necessary for HA inhibition by MU, and two hydroxy groups inhibited HA synthesis more strongly than MU.
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4-Methylumbelliferone, a hyaluronan synthase suppressor, enhances the anticancer activity of gemcitabine in human pancreatic cancer cells
Cancer Chemotherapy and Pharmacology, 2006Co-Authors: Hideaki Nakazawa, Keiichi Takagaki, Atsushi Kon, Shuichi Yoshihara, Daisuke Kudo, Ikuko Kakizaki, Hajime Morohashi, Mutsuo SasakiAbstract: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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a hyaluronan synthase suppressor 4 methylumbelliferone inhibits liver metastasis of melanoma cells
FEBS Letters, 2005Co-Authors: Shuichi Yoshihara, Masahiko Endo, Atsushi Kon, Daisuke Kudo, Hideaki Nakazawa, Ikuko Kakizaki, Mutsuo Sasaki, Keiichi TakagakiAbstract:4-Methylumbelliferone (MU) inhibits the cell surface hyaluronan (HA) formation, and that such inhibition results in suppression of adhesion and locomotion of cultured melanoma cells. Here, we examine the effect of MU on melanoma cell metastasis in vivo. MU-treated melanoma cells showed both decreased cell surface HA formation and suppression of liver metastasis after injection into the mice. Oral administration of MU to mice decreased tissue HA content. These HA knock-down mice displayed suppressed liver metastasis. Thus, both cell surface HA of melanoma cells and recipient liver HA can promote liver metastasis, indicating that MU has potential as an anti-metastatic agent.
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effect of a hyaluronan synthase suppressor 4 methylumbelliferone on b16f 10 melanoma cell adhesion and locomotion
Biochemical and Biophysical Research Communications, 2004Co-Authors: Daisuke Kudo, Masahiko Endo, Atsushi Kon, Shuichi Yoshihara, Ikuko Kakizaki, Mutsuo Sasaki, Keiichi TakagakiAbstract:Hyaluronan (HA) is a ubiquitous, major component of the extracellular matrix. It is involved in cell adhesion and locomotion, and hence in tumor metastasis. We have previously reported that 4-Methylumbelliferone (MU) inhibits HA synthesis and may be a useful tool for examining the functions of HA. We here demonstrate that the formation of cell surface HA by melanoma cells and its release into the culture medium are inhibited by MU. Adhesion and locomotion assays revealed that the adhesion and locomotion of melanoma cells were dose-dependently inhibited by MU. Conversely, treatment with exogenous HA enhanced both adhesion and locomotion. Thus, preventing the formation of cell surface HA reduced both the adhesion and locomotion of melanoma cells, suggesting that MU may act as an inhibitor of tumor metastasis.
Shuichi Yoshihara - One of the best experts on this subject based on the ideXlab platform.
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study of hyaluronan synthase inhibitor 4 methylumbelliferone derivatives on human pancreatic cancer cell kp1 nl
Biochemical and Biophysical Research Communications, 2006Co-Authors: Hajime Morohashi, Atsushi Kon, Shuichi Yoshihara, Ikuko Kakizaki, Mutsuo Sasaki, Makoto Nakai, Masanori Yamaguchi, Keiichi TakagakiAbstract:The structure of 4-Methylumbelliferone (MU) consists of coumarin with 4-methyl group and 7-hydroxy group. MU inhibits HA synthesis and pericellular HA matrix formation. In this study, we used 10 MU derivatives which have hydroxy groups and methyl groups at various positions of coumarin to investigate a more effective HA inhibitor than MU. First, human pancreatic cancer cell (KP1-NL) growth assay was analyzed by Alamar Blue to determine the non-toxic concentration of MU derivatives, and the inhibitory effect on HA synthesis in the cell cultures was analyzed by HA measuring kit. Next, cell surfaces of cancer cells were analyzed by particle-exclusion assay. In conclusion, both hydroxy and methyl groups are necessary for HA inhibition by MU, and two hydroxy groups inhibited HA synthesis more strongly than MU.
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4-Methylumbelliferone, a hyaluronan synthase suppressor, enhances the anticancer activity of gemcitabine in human pancreatic cancer cells
Cancer Chemotherapy and Pharmacology, 2006Co-Authors: Hideaki Nakazawa, Keiichi Takagaki, Atsushi Kon, Shuichi Yoshihara, Daisuke Kudo, Ikuko Kakizaki, Hajime Morohashi, Mutsuo SasakiAbstract: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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a hyaluronan synthase suppressor 4 methylumbelliferone inhibits liver metastasis of melanoma cells
FEBS Letters, 2005Co-Authors: Shuichi Yoshihara, Masahiko Endo, Atsushi Kon, Daisuke Kudo, Hideaki Nakazawa, Ikuko Kakizaki, Mutsuo Sasaki, Keiichi TakagakiAbstract:4-Methylumbelliferone (MU) inhibits the cell surface hyaluronan (HA) formation, and that such inhibition results in suppression of adhesion and locomotion of cultured melanoma cells. Here, we examine the effect of MU on melanoma cell metastasis in vivo. MU-treated melanoma cells showed both decreased cell surface HA formation and suppression of liver metastasis after injection into the mice. Oral administration of MU to mice decreased tissue HA content. These HA knock-down mice displayed suppressed liver metastasis. Thus, both cell surface HA of melanoma cells and recipient liver HA can promote liver metastasis, indicating that MU has potential as an anti-metastatic agent.
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effect of a hyaluronan synthase suppressor 4 methylumbelliferone on b16f 10 melanoma cell adhesion and locomotion
Biochemical and Biophysical Research Communications, 2004Co-Authors: Daisuke Kudo, Masahiko Endo, Atsushi Kon, Shuichi Yoshihara, Ikuko Kakizaki, Mutsuo Sasaki, Keiichi TakagakiAbstract:Hyaluronan (HA) is a ubiquitous, major component of the extracellular matrix. It is involved in cell adhesion and locomotion, and hence in tumor metastasis. We have previously reported that 4-Methylumbelliferone (MU) inhibits HA synthesis and may be a useful tool for examining the functions of HA. We here demonstrate that the formation of cell surface HA by melanoma cells and its release into the culture medium are inhibited by MU. Adhesion and locomotion assays revealed that the adhesion and locomotion of melanoma cells were dose-dependently inhibited by MU. Conversely, treatment with exogenous HA enhanced both adhesion and locomotion. Thus, preventing the formation of cell surface HA reduced both the adhesion and locomotion of melanoma cells, suggesting that MU may act as an inhibitor of tumor metastasis.
