Fibrotic Effects of Arecoline N-Oxide in Oral Potentially Malignant Disorders
The metabolites of environmental chemicals play key roles in carcinogenesis. Areca nut is strongly associated with the development of oral potentially malignant disorders (OPMD) or cancer. The main alkaloid in the areca nut is arecoline, which is highly cytotoxic and genotoxic. Arecoline N-oxide, a...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Kuo, Tzer-Min [verfasserIn] |
|---|
| Format: |
Artikel |
|---|---|
| Sprache: |
Englisch |
| Erschienen: |
2015 |
|---|
| Schlagwörter: |
Matrix Metalloproteinase 9 - genetics Cyclic N-Oxides - adverse effects Matrix Metalloproteinase 9 - metabolism |
|---|
| Übergeordnetes Werk: |
Enthalten in: Journal of agricultural and food chemistry - Columbus, Ohio : American Chemical Soc., 1953, 63(2015), 24, Seite 5787 |
|---|---|
| Übergeordnetes Werk: |
volume:63 ; year:2015 ; number:24 ; pages:5787 |
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| 520 | |a The metabolites of environmental chemicals play key roles in carcinogenesis. Areca nut is strongly associated with the development of oral potentially malignant disorders (OPMD) or cancer. The main alkaloid in the areca nut is arecoline, which is highly cytotoxic and genotoxic. Arecoline N-oxide, a metabolite of areca nut alkaloids, which has been identified in animal urine, has been shown to induce mutagenicity in bacteria. In this study, it was found that its protein adduct could be detected in oral keratinocytes treated with areca nut extract. Increased collagen expression and severity of squamous hyperplasia were observed in arecoline N-oxide treated mice. In cultured oral fibroblasts, arecoline N-oxide showed stronger effects on the increase of fibrotic related genes including TGF-beta1, S100A4, MMP-9, IL-6, and fibronectin and a decrease of E-cadherin as compared with arecoline. Finally, arecoline N-oxide stimulation effectively increased the DNA damage marker, gamma-H2A.X, both in vitro and in vivo. Taken together, these results indicate that arecoline N-oxide shows a high potential for the induction of OPMD. | ||
| 650 | 4 | |a Interleukin-6 - genetics | |
| 650 | 4 | |a Matrix Metalloproteinase 9 - genetics | |
| 650 | 4 | |a Areca - adverse effects | |
| 650 | 4 | |a Arecoline - adverse effects | |
| 650 | 4 | |a Cyclic N-Oxides - adverse effects | |
| 650 | 4 | |a Mouth Diseases - etiology | |
| 650 | 4 | |a Matrix Metalloproteinase 9 - metabolism | |
| 650 | 4 | |a Cyclic N-Oxides - metabolism | |
| 650 | 4 | |a Fibroblasts - metabolism | |
| 650 | 4 | |a Fibrosis - genetics | |
| 650 | 4 | |a Arecoline - analogs & derivatives | |
| 650 | 4 | |a Fruit - chemistry | |
| 650 | 4 | |a Mouth Diseases - metabolism | |
| 650 | 4 | |a Fruit - metabolism | |
| 650 | 4 | |a Fruit - adverse effects | |
| 650 | 4 | |a Fibrosis - etiology | |
| 650 | 4 | |a Arecoline - metabolism | |
| 650 | 4 | |a Interleukin-6 - metabolism | |
| 650 | 4 | |a Fibrosis - metabolism | |
| 650 | 4 | |a Areca - metabolism | |
| 650 | 4 | |a Areca - chemistry | |
| 650 | 4 | |a Mouth Diseases - genetics | |
| 700 | 1 | |a Luo, Shun-Yuan |4 oth | |
| 700 | 1 | |a Chiang, Shang-Lun |4 oth | |
| 700 | 1 | |a Yeh, Kun-Tu |4 oth | |
| 700 | 1 | |a Hsu, Hui-Ting |4 oth | |
| 700 | 1 | |a Wu, Cheng-Tien |4 oth | |
| 700 | 1 | |a Lu, Chi-Yu |4 oth | |
| 700 | 1 | |a Tsai, Ming-Hsui |4 oth | |
| 700 | 1 | |a Chang, Jan-Gowth |4 oth | |
| 700 | 1 | |a Ko, Ying-Chin |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of agricultural and food chemistry |d Columbus, Ohio : American Chemical Soc., 1953 |g 63(2015), 24, Seite 5787 |w (DE-627)129602795 |w (DE-600)241619-0 |w (DE-576)015096610 |x 0021-8561 |7 nnns |
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PQ20160617 (DE-627)OLC1963013255 (DE-599)GBVOLC1963013255 (PRQ)p1120-f9e4af689575bd511d107d4813cf0b79585e06399ce840564bf6c7f2575a7cfd0 (KEY)0011841920150000063002405787fibroticeffectsofarecolinenoxideinoralpotentiallym DE-627 ger DE-627 rakwb eng 630 640 540 DNB 58.27 bkl 58.34 bkl 42.63 bkl Kuo, Tzer-Min verfasserin aut Fibrotic Effects of Arecoline N-Oxide in Oral Potentially Malignant Disorders 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier The metabolites of environmental chemicals play key roles in carcinogenesis. Areca nut is strongly associated with the development of oral potentially malignant disorders (OPMD) or cancer. The main alkaloid in the areca nut is arecoline, which is highly cytotoxic and genotoxic. Arecoline N-oxide, a metabolite of areca nut alkaloids, which has been identified in animal urine, has been shown to induce mutagenicity in bacteria. In this study, it was found that its protein adduct could be detected in oral keratinocytes treated with areca nut extract. Increased collagen expression and severity of squamous hyperplasia were observed in arecoline N-oxide treated mice. In cultured oral fibroblasts, arecoline N-oxide showed stronger effects on the increase of fibrotic related genes including TGF-beta1, S100A4, MMP-9, IL-6, and fibronectin and a decrease of E-cadherin as compared with arecoline. Finally, arecoline N-oxide stimulation effectively increased the DNA damage marker, gamma-H2A.X, both in vitro and in vivo. Taken together, these results indicate that arecoline N-oxide shows a high potential for the induction of OPMD. Interleukin-6 - genetics Matrix Metalloproteinase 9 - genetics Areca - adverse effects Arecoline - adverse effects Cyclic N-Oxides - adverse effects Mouth Diseases - etiology Matrix Metalloproteinase 9 - metabolism Cyclic N-Oxides - metabolism Fibroblasts - metabolism Fibrosis - genetics Arecoline - analogs & derivatives Fruit - chemistry Mouth Diseases - metabolism Fruit - metabolism Fruit - adverse effects Fibrosis - etiology Arecoline - metabolism Interleukin-6 - metabolism Fibrosis - metabolism Areca - metabolism Areca - chemistry Mouth Diseases - genetics Luo, Shun-Yuan oth Chiang, Shang-Lun oth Yeh, Kun-Tu oth Hsu, Hui-Ting oth Wu, Cheng-Tien oth Lu, Chi-Yu oth Tsai, Ming-Hsui oth Chang, Jan-Gowth oth Ko, Ying-Chin oth Enthalten in Journal of agricultural and food chemistry Columbus, Ohio : American Chemical Soc., 1953 63(2015), 24, Seite 5787 (DE-627)129602795 (DE-600)241619-0 (DE-576)015096610 0021-8561 nnns volume:63 year:2015 number:24 pages:5787 http://www.ncbi.nlm.nih.gov/pubmed/26061808 GBV_USEFLAG_A SYSFLAG_A GBV_OLC SSG-OLC-TEC SSG-OLC-CHE SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-FOR GBV_ILN_70 GBV_ILN_2006 GBV_ILN_4219 58.27 AVZ 58.34 AVZ 42.63 AVZ AR 63 2015 24 5787 |
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PQ20160617 (DE-627)OLC1963013255 (DE-599)GBVOLC1963013255 (PRQ)p1120-f9e4af689575bd511d107d4813cf0b79585e06399ce840564bf6c7f2575a7cfd0 (KEY)0011841920150000063002405787fibroticeffectsofarecolinenoxideinoralpotentiallym DE-627 ger DE-627 rakwb eng 630 640 540 DNB 58.27 bkl 58.34 bkl 42.63 bkl Kuo, Tzer-Min verfasserin aut Fibrotic Effects of Arecoline N-Oxide in Oral Potentially Malignant Disorders 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier The metabolites of environmental chemicals play key roles in carcinogenesis. Areca nut is strongly associated with the development of oral potentially malignant disorders (OPMD) or cancer. The main alkaloid in the areca nut is arecoline, which is highly cytotoxic and genotoxic. Arecoline N-oxide, a metabolite of areca nut alkaloids, which has been identified in animal urine, has been shown to induce mutagenicity in bacteria. In this study, it was found that its protein adduct could be detected in oral keratinocytes treated with areca nut extract. Increased collagen expression and severity of squamous hyperplasia were observed in arecoline N-oxide treated mice. In cultured oral fibroblasts, arecoline N-oxide showed stronger effects on the increase of fibrotic related genes including TGF-beta1, S100A4, MMP-9, IL-6, and fibronectin and a decrease of E-cadherin as compared with arecoline. Finally, arecoline N-oxide stimulation effectively increased the DNA damage marker, gamma-H2A.X, both in vitro and in vivo. Taken together, these results indicate that arecoline N-oxide shows a high potential for the induction of OPMD. Interleukin-6 - genetics Matrix Metalloproteinase 9 - genetics Areca - adverse effects Arecoline - adverse effects Cyclic N-Oxides - adverse effects Mouth Diseases - etiology Matrix Metalloproteinase 9 - metabolism Cyclic N-Oxides - metabolism Fibroblasts - metabolism Fibrosis - genetics Arecoline - analogs & derivatives Fruit - chemistry Mouth Diseases - metabolism Fruit - metabolism Fruit - adverse effects Fibrosis - etiology Arecoline - metabolism Interleukin-6 - metabolism Fibrosis - metabolism Areca - metabolism Areca - chemistry Mouth Diseases - genetics Luo, Shun-Yuan oth Chiang, Shang-Lun oth Yeh, Kun-Tu oth Hsu, Hui-Ting oth Wu, Cheng-Tien oth Lu, Chi-Yu oth Tsai, Ming-Hsui oth Chang, Jan-Gowth oth Ko, Ying-Chin oth Enthalten in Journal of agricultural and food chemistry Columbus, Ohio : American Chemical Soc., 1953 63(2015), 24, Seite 5787 (DE-627)129602795 (DE-600)241619-0 (DE-576)015096610 0021-8561 nnns volume:63 year:2015 number:24 pages:5787 http://www.ncbi.nlm.nih.gov/pubmed/26061808 GBV_USEFLAG_A SYSFLAG_A GBV_OLC SSG-OLC-TEC SSG-OLC-CHE SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-FOR GBV_ILN_70 GBV_ILN_2006 GBV_ILN_4219 58.27 AVZ 58.34 AVZ 42.63 AVZ AR 63 2015 24 5787 |
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PQ20160617 (DE-627)OLC1963013255 (DE-599)GBVOLC1963013255 (PRQ)p1120-f9e4af689575bd511d107d4813cf0b79585e06399ce840564bf6c7f2575a7cfd0 (KEY)0011841920150000063002405787fibroticeffectsofarecolinenoxideinoralpotentiallym DE-627 ger DE-627 rakwb eng 630 640 540 DNB 58.27 bkl 58.34 bkl 42.63 bkl Kuo, Tzer-Min verfasserin aut Fibrotic Effects of Arecoline N-Oxide in Oral Potentially Malignant Disorders 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier The metabolites of environmental chemicals play key roles in carcinogenesis. Areca nut is strongly associated with the development of oral potentially malignant disorders (OPMD) or cancer. The main alkaloid in the areca nut is arecoline, which is highly cytotoxic and genotoxic. Arecoline N-oxide, a metabolite of areca nut alkaloids, which has been identified in animal urine, has been shown to induce mutagenicity in bacteria. In this study, it was found that its protein adduct could be detected in oral keratinocytes treated with areca nut extract. Increased collagen expression and severity of squamous hyperplasia were observed in arecoline N-oxide treated mice. In cultured oral fibroblasts, arecoline N-oxide showed stronger effects on the increase of fibrotic related genes including TGF-beta1, S100A4, MMP-9, IL-6, and fibronectin and a decrease of E-cadherin as compared with arecoline. Finally, arecoline N-oxide stimulation effectively increased the DNA damage marker, gamma-H2A.X, both in vitro and in vivo. Taken together, these results indicate that arecoline N-oxide shows a high potential for the induction of OPMD. Interleukin-6 - genetics Matrix Metalloproteinase 9 - genetics Areca - adverse effects Arecoline - adverse effects Cyclic N-Oxides - adverse effects Mouth Diseases - etiology Matrix Metalloproteinase 9 - metabolism Cyclic N-Oxides - metabolism Fibroblasts - metabolism Fibrosis - genetics Arecoline - analogs & derivatives Fruit - chemistry Mouth Diseases - metabolism Fruit - metabolism Fruit - adverse effects Fibrosis - etiology Arecoline - metabolism Interleukin-6 - metabolism Fibrosis - metabolism Areca - metabolism Areca - chemistry Mouth Diseases - genetics Luo, Shun-Yuan oth Chiang, Shang-Lun oth Yeh, Kun-Tu oth Hsu, Hui-Ting oth Wu, Cheng-Tien oth Lu, Chi-Yu oth Tsai, Ming-Hsui oth Chang, Jan-Gowth oth Ko, Ying-Chin oth Enthalten in Journal of agricultural and food chemistry Columbus, Ohio : American Chemical Soc., 1953 63(2015), 24, Seite 5787 (DE-627)129602795 (DE-600)241619-0 (DE-576)015096610 0021-8561 nnns volume:63 year:2015 number:24 pages:5787 http://www.ncbi.nlm.nih.gov/pubmed/26061808 GBV_USEFLAG_A SYSFLAG_A GBV_OLC SSG-OLC-TEC SSG-OLC-CHE SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-FOR GBV_ILN_70 GBV_ILN_2006 GBV_ILN_4219 58.27 AVZ 58.34 AVZ 42.63 AVZ AR 63 2015 24 5787 |
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PQ20160617 (DE-627)OLC1963013255 (DE-599)GBVOLC1963013255 (PRQ)p1120-f9e4af689575bd511d107d4813cf0b79585e06399ce840564bf6c7f2575a7cfd0 (KEY)0011841920150000063002405787fibroticeffectsofarecolinenoxideinoralpotentiallym DE-627 ger DE-627 rakwb eng 630 640 540 DNB 58.27 bkl 58.34 bkl 42.63 bkl Kuo, Tzer-Min verfasserin aut Fibrotic Effects of Arecoline N-Oxide in Oral Potentially Malignant Disorders 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier The metabolites of environmental chemicals play key roles in carcinogenesis. Areca nut is strongly associated with the development of oral potentially malignant disorders (OPMD) or cancer. The main alkaloid in the areca nut is arecoline, which is highly cytotoxic and genotoxic. Arecoline N-oxide, a metabolite of areca nut alkaloids, which has been identified in animal urine, has been shown to induce mutagenicity in bacteria. In this study, it was found that its protein adduct could be detected in oral keratinocytes treated with areca nut extract. Increased collagen expression and severity of squamous hyperplasia were observed in arecoline N-oxide treated mice. In cultured oral fibroblasts, arecoline N-oxide showed stronger effects on the increase of fibrotic related genes including TGF-beta1, S100A4, MMP-9, IL-6, and fibronectin and a decrease of E-cadherin as compared with arecoline. Finally, arecoline N-oxide stimulation effectively increased the DNA damage marker, gamma-H2A.X, both in vitro and in vivo. Taken together, these results indicate that arecoline N-oxide shows a high potential for the induction of OPMD. Interleukin-6 - genetics Matrix Metalloproteinase 9 - genetics Areca - adverse effects Arecoline - adverse effects Cyclic N-Oxides - adverse effects Mouth Diseases - etiology Matrix Metalloproteinase 9 - metabolism Cyclic N-Oxides - metabolism Fibroblasts - metabolism Fibrosis - genetics Arecoline - analogs & derivatives Fruit - chemistry Mouth Diseases - metabolism Fruit - metabolism Fruit - adverse effects Fibrosis - etiology Arecoline - metabolism Interleukin-6 - metabolism Fibrosis - metabolism Areca - metabolism Areca - chemistry Mouth Diseases - genetics Luo, Shun-Yuan oth Chiang, Shang-Lun oth Yeh, Kun-Tu oth Hsu, Hui-Ting oth Wu, Cheng-Tien oth Lu, Chi-Yu oth Tsai, Ming-Hsui oth Chang, Jan-Gowth oth Ko, Ying-Chin oth Enthalten in Journal of agricultural and food chemistry Columbus, Ohio : American Chemical Soc., 1953 63(2015), 24, Seite 5787 (DE-627)129602795 (DE-600)241619-0 (DE-576)015096610 0021-8561 nnns volume:63 year:2015 number:24 pages:5787 http://www.ncbi.nlm.nih.gov/pubmed/26061808 GBV_USEFLAG_A SYSFLAG_A GBV_OLC SSG-OLC-TEC SSG-OLC-CHE SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-FOR GBV_ILN_70 GBV_ILN_2006 GBV_ILN_4219 58.27 AVZ 58.34 AVZ 42.63 AVZ AR 63 2015 24 5787 |
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PQ20160617 (DE-627)OLC1963013255 (DE-599)GBVOLC1963013255 (PRQ)p1120-f9e4af689575bd511d107d4813cf0b79585e06399ce840564bf6c7f2575a7cfd0 (KEY)0011841920150000063002405787fibroticeffectsofarecolinenoxideinoralpotentiallym DE-627 ger DE-627 rakwb eng 630 640 540 DNB 58.27 bkl 58.34 bkl 42.63 bkl Kuo, Tzer-Min verfasserin aut Fibrotic Effects of Arecoline N-Oxide in Oral Potentially Malignant Disorders 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier The metabolites of environmental chemicals play key roles in carcinogenesis. Areca nut is strongly associated with the development of oral potentially malignant disorders (OPMD) or cancer. The main alkaloid in the areca nut is arecoline, which is highly cytotoxic and genotoxic. Arecoline N-oxide, a metabolite of areca nut alkaloids, which has been identified in animal urine, has been shown to induce mutagenicity in bacteria. In this study, it was found that its protein adduct could be detected in oral keratinocytes treated with areca nut extract. Increased collagen expression and severity of squamous hyperplasia were observed in arecoline N-oxide treated mice. In cultured oral fibroblasts, arecoline N-oxide showed stronger effects on the increase of fibrotic related genes including TGF-beta1, S100A4, MMP-9, IL-6, and fibronectin and a decrease of E-cadherin as compared with arecoline. Finally, arecoline N-oxide stimulation effectively increased the DNA damage marker, gamma-H2A.X, both in vitro and in vivo. Taken together, these results indicate that arecoline N-oxide shows a high potential for the induction of OPMD. Interleukin-6 - genetics Matrix Metalloproteinase 9 - genetics Areca - adverse effects Arecoline - adverse effects Cyclic N-Oxides - adverse effects Mouth Diseases - etiology Matrix Metalloproteinase 9 - metabolism Cyclic N-Oxides - metabolism Fibroblasts - metabolism Fibrosis - genetics Arecoline - analogs & derivatives Fruit - chemistry Mouth Diseases - metabolism Fruit - metabolism Fruit - adverse effects Fibrosis - etiology Arecoline - metabolism Interleukin-6 - metabolism Fibrosis - metabolism Areca - metabolism Areca - chemistry Mouth Diseases - genetics Luo, Shun-Yuan oth Chiang, Shang-Lun oth Yeh, Kun-Tu oth Hsu, Hui-Ting oth Wu, Cheng-Tien oth Lu, Chi-Yu oth Tsai, Ming-Hsui oth Chang, Jan-Gowth oth Ko, Ying-Chin oth Enthalten in Journal of agricultural and food chemistry Columbus, Ohio : American Chemical Soc., 1953 63(2015), 24, Seite 5787 (DE-627)129602795 (DE-600)241619-0 (DE-576)015096610 0021-8561 nnns volume:63 year:2015 number:24 pages:5787 http://www.ncbi.nlm.nih.gov/pubmed/26061808 GBV_USEFLAG_A SYSFLAG_A GBV_OLC SSG-OLC-TEC SSG-OLC-CHE SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-FOR GBV_ILN_70 GBV_ILN_2006 GBV_ILN_4219 58.27 AVZ 58.34 AVZ 42.63 AVZ AR 63 2015 24 5787 |
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Interleukin-6 - genetics Matrix Metalloproteinase 9 - genetics Areca - adverse effects Arecoline - adverse effects Cyclic N-Oxides - adverse effects Mouth Diseases - etiology Matrix Metalloproteinase 9 - metabolism Cyclic N-Oxides - metabolism Fibroblasts - metabolism Fibrosis - genetics Arecoline - analogs & derivatives Fruit - chemistry Mouth Diseases - metabolism Fruit - metabolism Fruit - adverse effects Fibrosis - etiology Arecoline - metabolism Interleukin-6 - metabolism Fibrosis - metabolism Areca - metabolism Areca - chemistry Mouth Diseases - genetics |
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Kuo, Tzer-Min @@aut@@ Luo, Shun-Yuan @@oth@@ Chiang, Shang-Lun @@oth@@ Yeh, Kun-Tu @@oth@@ Hsu, Hui-Ting @@oth@@ Wu, Cheng-Tien @@oth@@ Lu, Chi-Yu @@oth@@ Tsai, Ming-Hsui @@oth@@ Chang, Jan-Gowth @@oth@@ Ko, Ying-Chin @@oth@@ |
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Kuo, Tzer-Min ddc 630 bkl 58.27 bkl 58.34 bkl 42.63 misc Interleukin-6 - genetics misc Matrix Metalloproteinase 9 - genetics misc Areca - adverse effects misc Arecoline - adverse effects misc Cyclic N-Oxides - adverse effects misc Mouth Diseases - etiology misc Matrix Metalloproteinase 9 - metabolism misc Cyclic N-Oxides - metabolism misc Fibroblasts - metabolism misc Fibrosis - genetics misc Arecoline - analogs & derivatives misc Fruit - chemistry misc Mouth Diseases - metabolism misc Fruit - metabolism misc Fruit - adverse effects misc Fibrosis - etiology misc Arecoline - metabolism misc Interleukin-6 - metabolism misc Fibrosis - metabolism misc Areca - metabolism misc Areca - chemistry misc Mouth Diseases - genetics Fibrotic Effects of Arecoline N-Oxide in Oral Potentially Malignant Disorders |
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630 640 540 DNB 58.27 bkl 58.34 bkl 42.63 bkl Fibrotic Effects of Arecoline N-Oxide in Oral Potentially Malignant Disorders Interleukin-6 - genetics Matrix Metalloproteinase 9 - genetics Areca - adverse effects Arecoline - adverse effects Cyclic N-Oxides - adverse effects Mouth Diseases - etiology Matrix Metalloproteinase 9 - metabolism Cyclic N-Oxides - metabolism Fibroblasts - metabolism Fibrosis - genetics Arecoline - analogs & derivatives Fruit - chemistry Mouth Diseases - metabolism Fruit - metabolism Fruit - adverse effects Fibrosis - etiology Arecoline - metabolism Interleukin-6 - metabolism Fibrosis - metabolism Areca - metabolism Areca - chemistry Mouth Diseases - genetics |
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fibrotic effects of arecoline n-oxide in oral potentially malignant disorders |
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Fibrotic Effects of Arecoline N-Oxide in Oral Potentially Malignant Disorders |
| abstract |
The metabolites of environmental chemicals play key roles in carcinogenesis. Areca nut is strongly associated with the development of oral potentially malignant disorders (OPMD) or cancer. The main alkaloid in the areca nut is arecoline, which is highly cytotoxic and genotoxic. Arecoline N-oxide, a metabolite of areca nut alkaloids, which has been identified in animal urine, has been shown to induce mutagenicity in bacteria. In this study, it was found that its protein adduct could be detected in oral keratinocytes treated with areca nut extract. Increased collagen expression and severity of squamous hyperplasia were observed in arecoline N-oxide treated mice. In cultured oral fibroblasts, arecoline N-oxide showed stronger effects on the increase of fibrotic related genes including TGF-beta1, S100A4, MMP-9, IL-6, and fibronectin and a decrease of E-cadherin as compared with arecoline. Finally, arecoline N-oxide stimulation effectively increased the DNA damage marker, gamma-H2A.X, both in vitro and in vivo. Taken together, these results indicate that arecoline N-oxide shows a high potential for the induction of OPMD. |
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The metabolites of environmental chemicals play key roles in carcinogenesis. Areca nut is strongly associated with the development of oral potentially malignant disorders (OPMD) or cancer. The main alkaloid in the areca nut is arecoline, which is highly cytotoxic and genotoxic. Arecoline N-oxide, a metabolite of areca nut alkaloids, which has been identified in animal urine, has been shown to induce mutagenicity in bacteria. In this study, it was found that its protein adduct could be detected in oral keratinocytes treated with areca nut extract. Increased collagen expression and severity of squamous hyperplasia were observed in arecoline N-oxide treated mice. In cultured oral fibroblasts, arecoline N-oxide showed stronger effects on the increase of fibrotic related genes including TGF-beta1, S100A4, MMP-9, IL-6, and fibronectin and a decrease of E-cadherin as compared with arecoline. Finally, arecoline N-oxide stimulation effectively increased the DNA damage marker, gamma-H2A.X, both in vitro and in vivo. Taken together, these results indicate that arecoline N-oxide shows a high potential for the induction of OPMD. |
| abstract_unstemmed |
The metabolites of environmental chemicals play key roles in carcinogenesis. Areca nut is strongly associated with the development of oral potentially malignant disorders (OPMD) or cancer. The main alkaloid in the areca nut is arecoline, which is highly cytotoxic and genotoxic. Arecoline N-oxide, a metabolite of areca nut alkaloids, which has been identified in animal urine, has been shown to induce mutagenicity in bacteria. In this study, it was found that its protein adduct could be detected in oral keratinocytes treated with areca nut extract. Increased collagen expression and severity of squamous hyperplasia were observed in arecoline N-oxide treated mice. In cultured oral fibroblasts, arecoline N-oxide showed stronger effects on the increase of fibrotic related genes including TGF-beta1, S100A4, MMP-9, IL-6, and fibronectin and a decrease of E-cadherin as compared with arecoline. Finally, arecoline N-oxide stimulation effectively increased the DNA damage marker, gamma-H2A.X, both in vitro and in vivo. Taken together, these results indicate that arecoline N-oxide shows a high potential for the induction of OPMD. |
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Fibrotic Effects of Arecoline N-Oxide in Oral Potentially Malignant Disorders |
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Areca nut is strongly associated with the development of oral potentially malignant disorders (OPMD) or cancer. The main alkaloid in the areca nut is arecoline, which is highly cytotoxic and genotoxic. Arecoline N-oxide, a metabolite of areca nut alkaloids, which has been identified in animal urine, has been shown to induce mutagenicity in bacteria. In this study, it was found that its protein adduct could be detected in oral keratinocytes treated with areca nut extract. Increased collagen expression and severity of squamous hyperplasia were observed in arecoline N-oxide treated mice. In cultured oral fibroblasts, arecoline N-oxide showed stronger effects on the increase of fibrotic related genes including TGF-beta1, S100A4, MMP-9, IL-6, and fibronectin and a decrease of E-cadherin as compared with arecoline. Finally, arecoline N-oxide stimulation effectively increased the DNA damage marker, gamma-H2A.X, both in vitro and in vivo. 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