Areca nut exposure increases secretion of tumor‐promoting cytokines in gingival fibroblasts that trigger DNA damage in oral keratinocytes
Molecular crosstalk between cancer cells and fibroblasts has been an emerging hot issue in understanding carcinogenesis. As oral submucous fibrosis (OSF) is an inflammatory fibrotic disease that can potentially transform into squamous cell carcinoma, OSF has been considered to be an appropriate mode...
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| Language: | English |
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John Wiley and Sons Inc.
2015
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4744697/ |
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pubmed-4744697 |
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pubmed-47446972016-02-18 Areca nut exposure increases secretion of tumor‐promoting cytokines in gingival fibroblasts that trigger DNA damage in oral keratinocytes Illeperuma, Rasika P. Kim, Do Kyeong Park, Young Jin Son, Hwa Kyung Kim, Jue Young Kim, Jinmi Lee, Doo Young Kim, Ki‐Yeol Jung, Da‐Woon Tilakaratne, Wanninayake M. Kim, Jin Carcinogenesis Molecular crosstalk between cancer cells and fibroblasts has been an emerging hot issue in understanding carcinogenesis. As oral submucous fibrosis (OSF) is an inflammatory fibrotic disease that can potentially transform into squamous cell carcinoma, OSF has been considered to be an appropriate model for studying the role of fibroblasts during early stage carcinogenesis. In this sense, this study aims at investigating whether areca nut (AN)‐exposed fibroblasts cause DNA damage of epithelial cells. For this study, immortalized hNOF (hTERT‐hNOF) was used. We found that the levels of GRO‐α, IL‐6 and IL‐8 increased in AN‐exposed fibroblasts. Cytokine secretion was reduced by antioxidants in AN‐exposed fibroblasts. Increase in DNA double strand breaks (DSB) and 8‐oxoG FITC‐conjugate was observed in immortalized human oral keratinocytes (IHOK) after the treatment of cytokines or a conditioned medium derived from AN‐exposed fibroblasts. Cytokine expression and DNA damage were also detected in OSF tissues. The DNA damage was reduced by neutralizing cytokines or antioxidant treatment. Generation of reactive oxygen species (ROS) and DNA damage response, triggered by cytokines, were abolished when NADPH oxidase (NOX) 1 and 4 were silenced in IHOK, indicating that cytokine‐triggered DNA damage was caused by ROS generation through NOX1 and NOX4. Taken together, this study provided strong evidence that blocking ROS generation might be a rewarding approach for cancer prevention and intervention in OSF. John Wiley and Sons Inc. 2015-06-24 2015-12-01 /pmc/articles/PMC4744697/ /pubmed/26076896 http://dx.doi.org/10.1002/ijc.29636 Text en © 2015 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Illeperuma, Rasika P. Kim, Do Kyeong Park, Young Jin Son, Hwa Kyung Kim, Jue Young Kim, Jinmi Lee, Doo Young Kim, Ki‐Yeol Jung, Da‐Woon Tilakaratne, Wanninayake M. Kim, Jin |
| spellingShingle |
Illeperuma, Rasika P. Kim, Do Kyeong Park, Young Jin Son, Hwa Kyung Kim, Jue Young Kim, Jinmi Lee, Doo Young Kim, Ki‐Yeol Jung, Da‐Woon Tilakaratne, Wanninayake M. Kim, Jin Areca nut exposure increases secretion of tumor‐promoting cytokines in gingival fibroblasts that trigger DNA damage in oral keratinocytes |
| author_facet |
Illeperuma, Rasika P. Kim, Do Kyeong Park, Young Jin Son, Hwa Kyung Kim, Jue Young Kim, Jinmi Lee, Doo Young Kim, Ki‐Yeol Jung, Da‐Woon Tilakaratne, Wanninayake M. Kim, Jin |
| author_sort |
Illeperuma, Rasika P. |
| title |
Areca nut exposure increases secretion of tumor‐promoting cytokines in gingival fibroblasts that trigger DNA damage in oral keratinocytes |
| title_short |
Areca nut exposure increases secretion of tumor‐promoting cytokines in gingival fibroblasts that trigger DNA damage in oral keratinocytes |
| title_full |
Areca nut exposure increases secretion of tumor‐promoting cytokines in gingival fibroblasts that trigger DNA damage in oral keratinocytes |
| title_fullStr |
Areca nut exposure increases secretion of tumor‐promoting cytokines in gingival fibroblasts that trigger DNA damage in oral keratinocytes |
| title_full_unstemmed |
Areca nut exposure increases secretion of tumor‐promoting cytokines in gingival fibroblasts that trigger DNA damage in oral keratinocytes |
| title_sort |
areca nut exposure increases secretion of tumor‐promoting cytokines in gingival fibroblasts that trigger dna damage in oral keratinocytes |
| description |
Molecular crosstalk between cancer cells and fibroblasts has been an emerging hot issue in understanding carcinogenesis. As oral submucous fibrosis (OSF) is an inflammatory fibrotic disease that can potentially transform into squamous cell carcinoma, OSF has been considered to be an appropriate model for studying the role of fibroblasts during early stage carcinogenesis. In this sense, this study aims at investigating whether areca nut (AN)‐exposed fibroblasts cause DNA damage of epithelial cells. For this study, immortalized hNOF (hTERT‐hNOF) was used. We found that the levels of GRO‐α, IL‐6 and IL‐8 increased in AN‐exposed fibroblasts. Cytokine secretion was reduced by antioxidants in AN‐exposed fibroblasts. Increase in DNA double strand breaks (DSB) and 8‐oxoG FITC‐conjugate was observed in immortalized human oral keratinocytes (IHOK) after the treatment of cytokines or a conditioned medium derived from AN‐exposed fibroblasts. Cytokine expression and DNA damage were also detected in OSF tissues. The DNA damage was reduced by neutralizing cytokines or antioxidant treatment. Generation of reactive oxygen species (ROS) and DNA damage response, triggered by cytokines, were abolished when NADPH oxidase (NOX) 1 and 4 were silenced in IHOK, indicating that cytokine‐triggered DNA damage was caused by ROS generation through NOX1 and NOX4. Taken together, this study provided strong evidence that blocking ROS generation might be a rewarding approach for cancer prevention and intervention in OSF. |
| publisher |
John Wiley and Sons Inc. |
| publishDate |
2015 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4744697/ |
| _version_ |
1613535052603326464 |