高浓度的抗坏血酸(即维生素C),诱导人胃癌细胞凋亡

High concentrations of ascorbic acid, through H(2)O(2),  induces apoptosis of human gastric cancer cell by p38-MAP kinase-dependent up-regulation of transferrin receptor

 

我们研究了抗坏血酸（AA）诱导人胃癌细胞AGS细胞凋亡的分子机制。高浓度（超过5mM）的AA通过增加转铁蛋白受体（TfR）表达和诱导AGS细胞凋亡而增加细胞铁摄取，其被过氧化氢酶抑制。

　

有趣的是，p38丝裂原活化蛋白激酶（MAPK）抑制剂通过AA抑制TfR的上调和增加细胞存活。 TfR-siRNA转染的细胞通过AA减少细胞凋亡。

　

H（2）O（2）增加AGS细胞中的TfR表达。总之，我们得出结论，高浓度的AA，通过H（2）O（2），通过p38-MAPK依赖性TfR上调诱导AGS细胞凋亡。

　

　

High concentrations of ascorbic acid, through H(2)O(2),  induces apoptosis of human gastric cancer cell by p38-MAP kinase-dependent up-regulation of transferrin receptor

  

We investigated the molecular mechanism by which ascorbic acid (AA) induces apoptosis in human gastric cancer cells, AGS cells. High concentration (more than 5mM) of AA increased cellular iron uptake by increasing transferrin receptor (TfR) expression and induced AGS cell apoptosis which was inhibited by catalase.

　

Interestingly, p38 mitogen-activated protein kinase (MAPK) inhibitor inhibited the upregulation of TfR and increased cell survival by AA. TfR-siRNA-transfected cells reduced apoptosis by AA. H(2)O(2) increased TfR expression in AGS cells. Taken together, we concluded that high concentration of AA, through H(2)O(2), induces apoptosis of AGS cells by p38-MAPK-dependent upregulation of TfR.

　

　

Article in Cancer letters 277(1):48-54 · May 2009 with 22 Reads

DOI: 10.1016/j.canlet.2008.11.020 · Source: PubMed

　

Ha YM1, Park MK, Kim HJ, Seo HG, Lee JH, Chang KC.

Department of Pharmacology, School of Medicine and Institute of Health Sciences, Gyeongsang National University, Jinju, Republic of Korea.

　

　

High concentrations of ascorbic acid induces apoptosis of human gastric cancer cell by p38-MAP kinase-dependent up-regulation of transferrin receptor | Request PDF  https://www.researchgate.net/publication/23699029_High_concentrations_of_ascorbic_acid_induces_apoptosis_of_human_gastric_cancer_cell_by_p38-MAP_kinase-dependent_up-regulation_of_transferrin_receptor

　

　

　

　

维生素C通过产生线粒体的ROS诱导AGS细胞凋亡

Vitamin C induces apoptosis in AGS cells via production of ROS of mitochondria

 

摘要

已经证明维生素C在各种肿瘤细胞系中表现出抗癌活性。但是，其具体的行动机制仍然未知。尽管近年来癌症患者的诊断和治疗已经显着改善，但仍然需要更安全和更具成本效益的治疗。因此，本研究检测了维生素C对胃癌细胞死亡的诱导作用及其作用机制。观察到维生素C对人胃癌细胞系AGS的细胞毒性依赖于细胞凋亡途径，包括半胱天冬酶级联，但不依赖于坏死性途径。已经证明，维生素C诱导的钙内流和ROS产生在诱导细胞凋亡中起关键作用。此外，维生素C治疗消除了AGS细胞中三磷酸腺苷（ATP）的产生，并且自噬途径可能参与该过程。总之，目前的研究表明，高剂量的维生素C可能通过线粒体功能障碍诱发胃癌细胞凋亡，包括钙内流，活性氧生成和ATP消耗。

　

　

Format: AbstractSend to

Oncol Lett. 2016 Nov;12(5):4270-4276. Epub 2016 Sep 29.

Vitamin C induces apoptosis in AGS cells via production of ROS of mitochondria.

　

Abstract

It has been demonstrated that vitamin C exhibits anti-cancer activity in various tumor cell lines; however, its specific mechanism of action remains unknown. Although the diagnosis and therapy of cancer patients have markedly improved in recent years, safer and more cost-effective treatments are still required. Therefore, the present study examined the effect of vitamin C on the induction of cell death in gastric cancer and its underlying mechanism of action. It was observed that the cytotoxicity of vitamin C on the human gastric cancer cell line AGS is dependent on the apoptotic pathway, including caspase cascades, but not on the necroptotic pathway. It was demonstrated that the vitamin C-induced calcium influx and ROS generation have critical roles in the induction of apoptosis. Furthermore, vitamin C treatment depleted adenosine triphosphate (ATP) production in AGS cells, and the autophagy pathway may be involved in this process. Taken together, the current study suggests that a high dose of vitamin C may induce gastric cancer cell apoptosis through the dysfunction of mitochondria, including calcium influx, reactive oxygen species generation and ATP depletion.

 

KEYWORDS:

apoptosis; reactive oxygen species; vitamin C

PMID: 27895802 PMCID: PMC5104267 DOI: 10.3892/ol.2016.5212

　

Lim JY1, Kim D2, Kim BR1, Jun JS1, Yeom JS1, Park JS1, Seo JH1, Park CH1, Woo HO1, Youn HS1, Baik SC3, Lee WK3, Cho MJ3, Rhee KH3.

Author information

1

Department of Pediatrics, Gyeonsang National University School of Medicine, Jinju, Gyeongsang 660-702, Republic of Korea; Institute of Health Science, Gyeongsang National University Hospital, Jinju, Gyeongsang 660-702, Republic of Korea.

2

Center for Integrative Rheumatoid Transcriptomics and Dynamics, The Catholic University of Korea, Seoul 06591, Republic of Korea.

3

Institute of Health Science, Gyeongsang National University Hospital, Jinju, Gyeongsang 660-702, Republic of Korea; Department of Microbiology, Gyeonsang National University School of Medicine, Jinju, Gyeongsang 660-702, Republic of Korea.

　

 

Vitamin C induces apoptosis in AGS cells via production of ROS of mitochondria. - PubMed - NCBI  https://www.ncbi.nlm.nih.gov/pubmed/27895802