Areca nut extracts exert different effects in oral cancer cells depending on serum concentration: A clue to the various oral alterations in betel quid chewers
Betel quid chewing is associated with various pathologic alterations in oral mucosa. However, the molecular mechanism behind so many contradictory alterations remains unclear. Here we aimed to build a model to facilitate the related studies in cultured cells. In our results, areca nut extract (ANE)...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2014-01-01
|
| Series: | Toxicology Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214750014001152 |
| _version_ | 1818011074841018368 |
|---|---|
| author | Wen-Tsai Ji Yao-Chi Chuang Han-Po Chen Ching-Chih Lee Jeff Yi-Fu Chen Sheng-Ru Yang Jung-Hua Chen Chun-Jen Wang Hau-Ren Chen |
| author_facet | Wen-Tsai Ji Yao-Chi Chuang Han-Po Chen Ching-Chih Lee Jeff Yi-Fu Chen Sheng-Ru Yang Jung-Hua Chen Chun-Jen Wang Hau-Ren Chen |
| author_sort | Wen-Tsai Ji |
| collection | DOAJ |
| description | Betel quid chewing is associated with various pathologic alterations in oral mucosa. However, the molecular mechanism behind so many contradictory alterations remains unclear. Here we aimed to build a model to facilitate the related studies in cultured cells. In our results, areca nut extract (ANE) was found to exert different effects in oral cells depending on the supplemented serum level. ANE strongly induced DNA damage, necrotic ballooning, and inflammatory cytokines under lower serum concentration while might convert to facilitate deregulated growth of serum-supplemented cells via modulating the activity/expression of factors such as E-cadherin and Snail. Despite ANE significantly activated NF-κB, a mediator critical for inflammation, inhibition of NF-κB did not prevent the activation of IL8 promoter. We further discovered Y705-dephosphorylated STAT3 might enhance IL8 transcription. Since necrosis and the inflammatory cytokines could cause massive inflammation, infiltration of interstitial fluid might potentiate cellular resistance against the acute cytotoxicity of ANE and further support the proliferation of transforming cells. Induction of VEGF and angiogenesis under lower serum condition also paved the way for cell growth and subsequent metastasis. Accordingly, we concluded that in correlation with serum infiltration ANE caused particular effects in oral cells and possibly the various clinicopathological alterations in vivo. |
| first_indexed | 2024-04-14T06:02:42Z |
| format | Article |
| id | doaj.art-79e55e94edc24b0e98673a7b696434f4 |
| institution | Directory Open Access Journal |
| issn | 2214-7500 |
| language | English |
| last_indexed | 2024-04-14T06:02:42Z |
| publishDate | 2014-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Toxicology Reports |
| spelling | doaj.art-79e55e94edc24b0e98673a7b696434f42022-12-22T02:08:41ZengElsevierToxicology Reports2214-75002014-01-011C1087109510.1016/j.toxrep.2014.10.018Areca nut extracts exert different effects in oral cancer cells depending on serum concentration: A clue to the various oral alterations in betel quid chewersWen-Tsai Ji0Yao-Chi Chuang1Han-Po Chen2Ching-Chih Lee3Jeff Yi-Fu Chen4Sheng-Ru Yang5Jung-Hua Chen6Chun-Jen Wang7Hau-Ren Chen8Department of Urology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, TaiwanDepartment of Urology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, TaiwanDepartment of Life Science, Institute of Molecular Biology and Institute of Biomedical Science, National Chung Cheng University, Min-Hsiung, Chia-Yi, TaiwanDepartment of Otolaryngology, Buddhist Dalin Tzu Chi General Hospital, Chia-Yi, TaiwanDepartment of Biotechnology, Kaohsiung Medical University, Kaohsiung, TaiwanDepartment of Life Science, Institute of Molecular Biology and Institute of Biomedical Science, National Chung Cheng University, Min-Hsiung, Chia-Yi, TaiwanDepartment of Life Science, Institute of Molecular Biology and Institute of Biomedical Science, National Chung Cheng University, Min-Hsiung, Chia-Yi, TaiwanDepartment of Life Science, Institute of Molecular Biology and Institute of Biomedical Science, National Chung Cheng University, Min-Hsiung, Chia-Yi, TaiwanDepartment of Life Science, Institute of Molecular Biology and Institute of Biomedical Science, National Chung Cheng University, Min-Hsiung, Chia-Yi, TaiwanBetel quid chewing is associated with various pathologic alterations in oral mucosa. However, the molecular mechanism behind so many contradictory alterations remains unclear. Here we aimed to build a model to facilitate the related studies in cultured cells. In our results, areca nut extract (ANE) was found to exert different effects in oral cells depending on the supplemented serum level. ANE strongly induced DNA damage, necrotic ballooning, and inflammatory cytokines under lower serum concentration while might convert to facilitate deregulated growth of serum-supplemented cells via modulating the activity/expression of factors such as E-cadherin and Snail. Despite ANE significantly activated NF-κB, a mediator critical for inflammation, inhibition of NF-κB did not prevent the activation of IL8 promoter. We further discovered Y705-dephosphorylated STAT3 might enhance IL8 transcription. Since necrosis and the inflammatory cytokines could cause massive inflammation, infiltration of interstitial fluid might potentiate cellular resistance against the acute cytotoxicity of ANE and further support the proliferation of transforming cells. Induction of VEGF and angiogenesis under lower serum condition also paved the way for cell growth and subsequent metastasis. Accordingly, we concluded that in correlation with serum infiltration ANE caused particular effects in oral cells and possibly the various clinicopathological alterations in vivo.http://www.sciencedirect.com/science/article/pii/S2214750014001152Areca nut extract (ANE)NecrosisInflammationSerumSTAT3 |
| spellingShingle | Wen-Tsai Ji Yao-Chi Chuang Han-Po Chen Ching-Chih Lee Jeff Yi-Fu Chen Sheng-Ru Yang Jung-Hua Chen Chun-Jen Wang Hau-Ren Chen Areca nut extracts exert different effects in oral cancer cells depending on serum concentration: A clue to the various oral alterations in betel quid chewers Toxicology Reports Areca nut extract (ANE) Necrosis Inflammation Serum STAT3 |
| title | Areca nut extracts exert different effects in oral cancer cells depending on serum concentration: A clue to the various oral alterations in betel quid chewers |
| title_full | Areca nut extracts exert different effects in oral cancer cells depending on serum concentration: A clue to the various oral alterations in betel quid chewers |
| title_fullStr | Areca nut extracts exert different effects in oral cancer cells depending on serum concentration: A clue to the various oral alterations in betel quid chewers |
| title_full_unstemmed | Areca nut extracts exert different effects in oral cancer cells depending on serum concentration: A clue to the various oral alterations in betel quid chewers |
| title_short | Areca nut extracts exert different effects in oral cancer cells depending on serum concentration: A clue to the various oral alterations in betel quid chewers |
| title_sort | areca nut extracts exert different effects in oral cancer cells depending on serum concentration a clue to the various oral alterations in betel quid chewers |
| topic | Areca nut extract (ANE) Necrosis Inflammation Serum STAT3 |
| url | http://www.sciencedirect.com/science/article/pii/S2214750014001152 |
| work_keys_str_mv | AT wentsaiji arecanutextractsexertdifferenteffectsinoralcancercellsdependingonserumconcentrationacluetothevariousoralalterationsinbetelquidchewers AT yaochichuang arecanutextractsexertdifferenteffectsinoralcancercellsdependingonserumconcentrationacluetothevariousoralalterationsinbetelquidchewers AT hanpochen arecanutextractsexertdifferenteffectsinoralcancercellsdependingonserumconcentrationacluetothevariousoralalterationsinbetelquidchewers AT chingchihlee arecanutextractsexertdifferenteffectsinoralcancercellsdependingonserumconcentrationacluetothevariousoralalterationsinbetelquidchewers AT jeffyifuchen arecanutextractsexertdifferenteffectsinoralcancercellsdependingonserumconcentrationacluetothevariousoralalterationsinbetelquidchewers AT shengruyang arecanutextractsexertdifferenteffectsinoralcancercellsdependingonserumconcentrationacluetothevariousoralalterationsinbetelquidchewers AT junghuachen arecanutextractsexertdifferenteffectsinoralcancercellsdependingonserumconcentrationacluetothevariousoralalterationsinbetelquidchewers AT chunjenwang arecanutextractsexertdifferenteffectsinoralcancercellsdependingonserumconcentrationacluetothevariousoralalterationsinbetelquidchewers AT haurenchen arecanutextractsexertdifferenteffectsinoralcancercellsdependingonserumconcentrationacluetothevariousoralalterationsinbetelquidchewers |