Toxic Effects of Arecoline on Human Stomach Mucosal Epithelial Cells

LI Jiaxu; CHENG Yuying; YANG Yang; WANG Biying; JIANG Yuzhen; CHEN Jianping; LI Pan; DU Bing

doi:10.13386/j.issn1002-0306.2023050244

Volume 45 Issue 9

Apr. 2024

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Science and Technology of Food Industry > 2024 > 45(9): 341-349. > DOI: 10.13386/j.issn1002-0306.2023050244

LI Jiaxu, CHENG Yuying, YANG Yang, et al. Toxic Effects of Arecoline on Human Stomach Mucosal Epithelial Cells[J]. Science and Technology of Food Industry, 2024, 45(9): 341−349. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2023050244.

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Toxic Effects of Arecoline on Human Stomach Mucosal Epithelial Cells

1.
College of Food Science, South China Agriculture University, Guangzhou 510642, China
2.
School of Chinese Medicine, University of Hong Kong, Hong Kong 999077, China

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Received Date: May 21, 2023
Available Online: March 07, 2024

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Abstract

Abstract

The purpose of this study was to look into the toxicity of arecoline on human stomach mucosal epithelial cells GES-1. GES-1 cells were treated with different concentrations (60, 90, 120, 150 μg/mL) of arecoline, detection of GES-1 cell viability, reactive oxygen species levels (ROS) and mitochondrial membrane potential (MMP). The levels of glutathione (GSH), superoxide dismutase (SOD), lactate dehydrogenase (LDH), adenosine triphosphate (ATP) enzymes were measured in GES-1 cellls. And the leves of tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β) were measured in GES-1 cells. Compared with the control group, the shape of GES-1 cells was altered after arecoline stimulation, with the lowest cell viability rate reduced to 24%, the highest reactive oxygen species level increased to 12.5 fold, and the lowest mitochondrial membrane potential decreased to 10.4%. Under 150 μg/mL arecoline stimulation, T-ATPase and Na⁺K⁺-ATPase activity decreased to 42.31% and 39.84%, GSH and SOD decreased by 40.23% and 34.1%, respectively, LDH increased by 30.46%, TNF-α, IL-6, VEGF and TGF-β levels increased by 4.67%, 10.2%, 23.14% and 22.83%. The results indicate that arecoline can produce oxidative stress and induce inflammatory factors that cause toxic damage to GES-1 cells.
- arecoline,
- human gastric mucosal epithelial cells GES-1,
- oxidative stress,
- mitochondria,
- cytotoxic

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[1]	LI L, LUO Z, LIU Y, et al. Screening and identification of the metabolites in rat plasma and urine after oral administration of Areca catechu L. nut extract by ultra-high-pressure liquid chromatography coupled with linear ion trap–orbitrap tandem mass spectrometry[J]. Molecules,2017,22(6):1026. doi: 10.3390/molecules22061026
[2]	IARC W G O T. Betel-quid and areca-nut chewing and some areca-nut derived nitrosamines[J]. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans,2004,85:1−334.
[3]	侯倩煜, 符礼顺, 梁焕宴, 等. LC-PDA测定槟榔、焦槟榔、大腹皮中4种生物碱的含量[J]. 中国现代应用药学,2023,40(4):443−447. [HOU Q Y, FU L S, LIANG H Y, et al. Determination of four alkaloids components in arecae semen, arecae semen tostum and arecae pericarpium by LC-PDA[J]. Chinese Journal of Modern Applied Pharmacy,2023,40(4):443−447.] HOU Q Y, FU L S, LIANG H Y, et al. Determination of four alkaloids components in arecae semen, arecae semen tostum and arecae pericarpium by LC-PDA[J]. Chinese Journal of Modern Applied Pharmacy, 2023, 40（4）: 443−447.
[4]	JENG J, CHANG M C, HAHN L J. Role of areca nut in betel quid-associated chemical carcinogenesis:Current awareness and future perspectives[J]. Oral Oncology,2001,37(6):477−492. doi: 10.1016/S1368-8375(01)00003-3
[5]	JENG J H, HAHN L J, LIN B R, et al. Effects of areca nut, inflorescence piper betle extracts and arecoline on cytotoxicity, total and unscheduled DNA synthesis in cultured gingival keratinocytes[J]. Journal of Oral Pathology & Medicine,1999,28(2):64−71.
[6]	PEARCE A K, HUMPHREY T C. Integrating stress-response and cell-cycle checkpoint pathways[J]. Trends in Cell Biology,2001,11(10):426−433. doi: 10.1016/S0962-8924(01)02119-5
[7]	WASSERMAN W W, FAHL W E. Functional antioxidant responsive elements[J]. Proceedings of the National Academy of Sciences,1997,94(10):5361−5366. doi: 10.1073/pnas.94.10.5361
[8]	GENESTRA M. Oxyl radicals, redox-sensitive signalling cascades and antioxidant[J]. Cellular Signalling,2007,19(9):1807−1819. doi: 10.1016/j.cellsig.2007.04.009
[9]	DASGUPTA R, SAHA I, PAL S, et al. Immunosuppression, hepatotoxicity and depression of antioxidant status by arecoline in albino mice[J]. Toxicology,2006,227(1-2):94−104. doi: 10.1016/j.tox.2006.07.016
[10]	SAHA I, CHATTERJI U, CHAUDHURI S S, et al. Ultrastructural and hormonal changes in the pineal–testicular axis following arecoline administration in rats[J]. Journal of Experimental Zoology Part A:Ecological Genetics and Physiology,2007,307(4):187−198.
[11]	CHANG M, WU H, LEE J, et al. The induction of prostaglandin E2 production, interleukin-6 production, cell cycle arrest, and cytotoxicity in primary oral keratinocytes and KB cancer cells by areca nut ingredients is differentially regulated by MEK/ERK activation[J]. Journal of Biological Chemistry,2004,279(49):50676−50683. doi: 10.1074/jbc.M404465200
[12]	TSAI C H, CHOU M Y, CHANG Y C. The induction of prostaglandin E2 production, interleukin-6 production, cell cycle arrest, and cytotoxicity in primary oral keratinocytes and KB cancer cells by areca nut ingredients is differentially regulated by MEK/ERK activation[J]. Journal of Oral Pathology & Medicine,2003,32(3):146−153.
[13]	JENG J, TSAI C L, HAHN L J, et al. Arecoline cytotoxicity on human oral mucosal fibroblasts related to cellular thiol and esterase activities[J]. Food and Chemical Toxicology,1999,37(7):751−756. doi: 10.1016/S0278-6915(99)00050-2
[14]	SUNDQVIST K, LIU Y, NAIR J, et al. Cytotoxic and genotoxic effects of areca nut-related compounds in cultured human buccal epithelial cells[J]. Cancer Research,1989,49(19):5294−5298.
[15]	KURKALANG S, BANERJEE A, GHOSHAL N, et al. Induction of chromosome instability and stomach cancer by altering the expression pattern of mitotic checkpoint genes in mice exposed to areca-nut[J]. BMC Cancer,2013,13(1):1−12. doi: 10.1186/1471-2407-13-1
[16]	BHIDE S V, GOTHOSKAR S V, SHIVAPURKAR N M. Arecoline tumorigenicity in Swiss strain mice on normal and vitamin B deficient diet[J]. Journal of Cancer Research and Clinical Oncology,1984,107:169−171. doi: 10.1007/BF01032602
[17]	DUNHAM L J, SNELL K C, STEWART H L. Brief communication:Argyrophilic carcinoids in two syrian hamsters (Mesocricetus auratus)[J]. Journal of the National Cancer Institute,1975,54(2):507−513.
[18]	冷彦, 王静, 吴文斗, 等. 高压脉冲电场预处理普洱熟茶对SD大鼠体内活性氧(ROS)水平的影响[J]. 西南农业学报,2021,34(6):1208−1214. [LENG Y, WANG J, WU W D, et al. Effect of pre-treatment of Pu'er tea by high voltage pulse eLectric field on reactive oxygen (ROS) levels in SD mice[J]. Southwest China Journal of Agricultural Sciences,2021,34(6):1208−1214.] LENG Y, WANG J, WU W D, et al. Effect of pre-treatment of Pu'er tea by high voltage pulse eLectric field on reactive oxygen （ROS） levels in SD mice[J]. Southwest China Journal of Agricultural Sciences, 2021, 34（6）: 1208−1214.
[19]	冼健安, 李彬, 郭慧, 等. JC-1标记的流式细胞术测定虾类血细胞的线粒体膜电位[J]. 水产科学,2013,32(3):157−160. [XIAN J A, LI B, GUO H, et al. Measurement of mitochondrial membrane electronic potential in shrimp haemocytes by JC-1 staining and flow cytometry[J]. Fisheries Science,2013,32(3):157−160.] XIAN J A, LI B, GUO H, et al. Measurement of mitochondrial membrane electronic potential in shrimp haemocytes by JC-1 staining and flow cytometry[J]. Fisheries Science, 2013, 32（3）: 157−160.
[20]	朱钦士. 低剂量的毒物对生物有益?——比较毒物的单相剂量效应理论和双相剂量效应理论(1)[J]. 生物学通报,2020,55(1):10−13. [ZHU Q S. Is a little bit of toxin good for you?-linear no-threshold model versus Hormesis model(1)[J]. Bulletin of Biology,2020,55(1):10−13.] ZHU Q S. Is a little bit of toxin good for you?-linear no-threshold model versus Hormesis model（1）[J]. Bulletin of Biology, 2020, 55（1）: 10−13.
[21]	WU J, LIU K, SHI X. The anti-inflammatory activity of several flavonoids isolated from Murraya paniculata on murine macrophage cell line and gastric epithelial cell (GES-1)[J]. Pharmaceutical Biology,2016,54(5):868−881. doi: 10.3109/13880209.2015.1089294
[22]	KONG D, WANG G, TANG Y, et al. Potential health risk of areca nut consumption:Hazardous effect of toxic alkaloids and aflatoxins on human digestive system[J]. Food Research International, 2022, 162(Pt A):112012.
[23]	RAY P D, HUANG B W, TSUJI Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling[J]. Cell Signal,2012,24(5):981−990. doi: 10.1016/j.cellsig.2012.01.008
[24]	许智, 吕逢源, 姜二辉, 等. 槟榔与细胞内活性氧及自噬的关系[J]. 华西口腔医学杂志,2020,38(1):80−85. [XU Z, LÜ F Y, JIANG E H, et al. Relationship among areca nut, intracellular reactive oxygen species, and autophagy[J]. West China Journal of Stomatology,2020,38(1):80−85.] XU Z, LÜ F Y, JIANG E H, et al. Relationship among areca nut, intracellular reactive oxygen species, and autophagy[J]. West China Journal of Stomatology, 2020, 38（1）: 80−85.
[25]	HUNG T C, HUANG L W, SU S J, et al. Hemeoxygenase-1 expression in response to arecoline-induced oxidative stress in human umbilical vein endothelial cells[J]. International Journal of Cardiology,2011,151(2):187−194. doi: 10.1016/j.ijcard.2010.05.015
[26]	JI W T, YANG S R, CHEN J Y, et al. Arecoline downregulates levels of p21 and p27 through the reactive oxygen species/mTOR complex 1 pathway and may contribute to oral squamous cell carcinoma[J]. Cancer Science,2012,103(7):1221−1229. doi: 10.1111/j.1349-7006.2012.02294.x
[27]	王小巍, 张红艳, 刘锐, 等. 谷胱甘肽的研究进展[J]. 中国药剂学杂志(网络版),2019,17(4):141−148. [WANG X W, ZHANG H Y, LIU R, et al. Progress in research of glutathione[J]. Chinese Journal of Pharmaceutics (Online Edition),2019,17(4):141−148.] WANG X W, ZHANG H Y, LIU R, et al. Progress in research of glutathione[J]. Chinese Journal of Pharmaceutics （Online Edition）, 2019, 17（4）: 141−148.
[28]	覃焱, 许海钊, 徐境懋, 等. 亚硒酸钠和硒代蛋氨酸对人结肠腺癌细胞的毒性作用[J]. 现代食品科技,2021,37(1):1−6. [TAN Y, XU H Z, XU J M, et al. Cytotoxicity in human colon adenocarcinoma Caco-2 cell induced by celenite and selenomethionine[J]. Modern Food Science and Technology,2021,37(1):1−6.] TAN Y, XU H Z, XU J M, et al. Cytotoxicity in human colon adenocarcinoma Caco-2 cell induced by celenite and selenomethionine[J]. Modern Food Science and Technology, 2021, 37（1）: 1−6.
[29]	LARID M D, WAKADE C, ALLEYNE C J, et al. Hemin-induced necroptosis involves glutathione depletion in mouse astrocytes[J]. Free Radical Biology and Medicine,2008,45(8):1103−1114. doi: 10.1016/j.freeradbiomed.2008.07.003
[30]	RUN M X, JUN J W, JING Y C, et al. Effects of arecoline on hepatic cytochrome P450 activity and oxidative stress[J]. Journal of Toxicological Sciences,2014,39(4):609−614. doi: 10.2131/jts.39.609
[31]	CHANG M C, HO Y S, LEE P H, et al. Areca nut extract and arecoline induced the cell cycle arrest but not apoptosis of cultured oral KB epithelial cells:Association of glutathione, reactive oxygen species and mitochondrial membrane potential[J]. Carcinogenesis,2001,22(9):1527−1535.
[32]	DING Y, YAO H, YAO Y, et al. Protection of dietary polyphenols against oral cancer[J]. Nutrients,2013,5(6):2173−2191.
[33]	ZHAO W, FENG H, SUN W, et al. Tert-butyl hydroperoxide (t-BHP) induced apoptosis and necroptosis in endothelial cells:Roles of NOX4 and mitochondrion[J]. Redox Biology,2017,11:524−534. doi: 10.1016/j.redox.2016.12.036
[34]	DERA A A, AL F M, OTIFI H, et al. Thymoquinone (Tq) protects necroptosis induced by autophagy/mitophagy-dependent oxidative stress in human bronchial epithelial cells exposed to cigarette smoke extract (CSE)[J]. Journal of Food Biochemistry,2020,44(9):e13366.
[35]	CHI Q, WANG D, HU X, et al. Hydrogen sulfide gas exposure induces necroptosis and promotes inflammation through the MAPK/NF-kappaB pathway in broiler spleen[J]. Oxidative Medicine and Cellular Longevity,2019,2019:8061823.
[36]	高世勇, 李丹. 肿瘤坏死因子与癌症相关研究进展[J]. 中国药理学通报,2020,36(9):1209−1213. [GAO S Y, LI D. Research advances in tumor necrosis factor and cancer[J]. Chinese Pharmacological Bulletin,2020,36(9):1209−1213.] GAO S Y, LI D. Research advances in tumor necrosis factor and cancer[J]. Chinese Pharmacological Bulletin, 2020, 36（9）: 1209−1213.
[37]	HARUN O R M, ALI M B, JESMIN, et al. Statistical meta-analysis to investigate the association between the interleukin-6 (IL-6) gene polymorphisms and cancer risk[J]. PLoS One,2021,16(3):e247055.
[38]	WEEKS B H, HE W, OLSON K L, et al. Inducible expression of transforming growth factor beta1 in papillomas causes rapid metastasis[J]. Cancer Research,2001,61(20):7435−7443.
[39]	刘晨, 隋红. TGF-β信号通路介导胃癌EMT的研究进展[J]. 现代肿瘤医学,2020,28(3):517−520. [LIU C, SUI H. Research progress on TGF-β signaling pathway in mediating EMT of gastric cancer[J]. Journal of Modern Oncology,2020,28(3):517−520.] LIU C, SUI H. Research progress on TGF-β signaling pathway in mediating EMT of gastric cancer[J]. Journal of Modern Oncology, 2020, 28（3）: 517−520.
[40]	CHANG L Y, WAN H C, LAI Y L, et al. Areca nut extracts increased the expression of cyclooxygenase-2, prostaglandin E2 and interleukin-1alpha in human immune cells via oxidative stress[J]. Archives of Oral Biology,2013,58(10):1523−1531. doi: 10.1016/j.archoralbio.2013.05.006
[41]	FAOUZI M, NEUPANE R P, YANG J, et al. Areca nut extracts mobilize calcium and release pro-inflammatory cytokines from various immune cells[J]. Scientific Reports,2018,8(1):1075. doi: 10.1038/s41598-017-18996-2
[42]	JENG J H, WANG Y J, CHIANG B L, et al. Roles of keratinocyte inflammation in oral cancer:Regulating the prostaglandin E2, Interleukin-6 and TNF-alpha production of oral epithelial cells by areca nut extract and arecoline[J]. Carcinogenesis,2003,24(8):1301−1315. doi: 10.1093/carcin/bgg083
[43]	LI Y C, CHENG A J, LEE L Y, et al. Multifaceted mechanisms of areca nuts in oral carcinogenesis:The molecular pathology from precancerous condition to malignant transformation[J]. Journal of Cancer,2019,10(17):4054−4062. doi: 10.7150/jca.29765
[44]	杨博, 符梦凡, 唐瞻贵. 槟榔碱及机械刺激构建大鼠口腔黏膜下纤维化模型[J]. 华西口腔医学杂志,2019,37(3):260−264. [YANG B, FU M F, TANG Z G. Rat model with oral submucous fibrosis induced by arecoline and mechanical stimulation[J]. West China Journal of Stomatology,2019,37(3):260−264.] YANG B, FU M F, TANG Z G. Rat model with oral submucous fibrosis induced by arecoline and mechanical stimulation[J]. West China Journal of Stomatology, 2019, 37（3）: 260−264.
[45]	LI L, HE Z, ZHU Y, et al. Hydrogen sulfide suppresses skin fibroblast proliferation via oxidative stress alleviation and necroptosis inhibition[J]. Oxidative Medicine and Cellular Longevity,2022,2022:7434733.
[46]	SHEN C, WANG C, HAN S, et al. Aldehyde dhydrogenase 2 deficiency negates chronic low-to-moderate alcohol consumption-induced cardioprotecion possibly via ROS-dependent apoptosis and RIP1/RIP3/MLKL-mediated necroptosis[J]. Biochimica Et Biophysica Acta-molecular Basis of Disease,2017,1863(8):1912−1918. doi: 10.1016/j.bbadis.2016.11.016

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