Reactive oxygen species induce apoptosis in selenite-treated colorectal cancer cells via PKD1/AKT signaling-mediated mitochondrial translocation of Bad
Main Article Content
Abstract
Mounting evidence shows that supranutritional selenite-induced Reactive Oxygen Species (ROS) could trigger colorectal cancer (CRC) cells apoptosis, however, the molecular mechanism underlying this effect remains unclear. To explore the detailed mechanism how ROS induced apoptosis in selenite-treated CRC cells, we investigated the role of AKT/Bad signaling-mediated mitochondrial cell death in selenite-treated CRC cells and xenograft tumors. First, we found that selenite exposure inhibited Bad phosphorylation, leading to mitochondrial translocation of Bad, which further triggers HCT116 and SW480 CRC cells apoptosis. Furthermore, we identified that AKT-mediated phosphorylation shown to repress Bad function by causing it dissociate from mitochondria and bind to 14-3-3 proteins in the cytoplasm. Additionally, we discovered that selenite-induced ROS cause AKT dephosphorylation by inhibiting the kinase activity of protein kinase D1 (PKD1) in CRC cells. We also corroborated our findings in vivo by performing immunohistochemistry experiments. Overall, these observations demonstrate that ROS could induce apoptosis through promoting the mitochondrial translocation of Bad by inhibiting PKD1/AKT signaling in selenite-treated CRC cells in vitro and in vivo.
Article Details
How to Cite
HUI, Kaiyuan.
Reactive oxygen species induce apoptosis in selenite-treated colorectal cancer cells via PKD1/AKT signaling-mediated mitochondrial translocation of Bad.
Medical Research Archives, [S.l.], n. 3, july 2016.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/547>. Date accessed: 27 dec. 2024.
Keywords
selenite; apoptosis; mitochondria; PKD1; Bad
Issue
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
Reference
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[2]Riaz M, Mehmood KT. SELENIUM IN HUMAN HEALTH AND DISEASE: A REVIEW. JPMI: Journal of Postgraduate Medical Institute 2012; 26(2).
[3]Sanmartín C, Plano D, Sharma AK, Palop JA. Selenium compounds, apoptosis and other types of cell death: an overview for cancer therapy. International journal of molecular sciences 2012; 13(8): 9649-9672.
[4]Rayman MP. Selenium and human health. The Lancet 2012; 379(9822): 1256-1268.
[5]Hui K, Yang Y, Shi K, Luo H, Duan J, An J, et al. The p38 MAPK-regulated PKD1/CREB/Bcl-2 pathway contributes to selenite-induced colorectal cancer cell apoptosis in vitro and in vivo. Cancer letters 2014; 354(1): 189-199.
[6]Luo H, Yang Y, Duan J, Wu P, Jiang Q, Xu C. PTEN-regulated AKT/FoxO3a/Bim signaling contributes to reactive oxygen species-mediated apoptosis in selenite-treated colorectal cancer cells. Cell death & disease 2013; 4(2): e481.
[7]Wu P, Shi KJ, An JJ, Ci YL, Li F, Hui KY, et al. The LEF1/CYLD axis and cIAPs regulate RIP1 deubiquitination and trigger apoptosis in selenite-treated colorectal cancer cells. Cell Death Dis 2014; 5: e1085.
[8]Shi K, Jiang Q, Li Z, Shan L, Li F, An J, et al. Sodium selenite alters microtubule assembly and induces apoptosis in vitro and in vivo. J Hematol Oncol 2013; 6(7).
[9]Shi K, An J, Shan L, Jiang Q, Li F, Ci Y, et al. Survivin-2B promotes autophagy by accumulating IKK alpha in the nucleus of selenite-treated NB4 cells. Cell Death Dis 2014; 5: e1071.
[10]An J, Shi K, Wei W, Hua F, Ci Y, Jiang Q, et al. The ROS/JNK/ATF2 pathway mediates selenite-induced leukemia NB4 cell cycle arrest and apoptosis in vitro and in vivo. Cell death & disease 2013; 4(12): e973.
[11]SF P, CY L, MJ H, SC T, DH K, FA C, et al. Curcumin-loaded nanoparticles enhance apoptotic cell death of U2OS human osteosarcoma cells through the Akt-Bad signaling pathway. International Journal of Oncology 2014; 44(1): 238-246.
[12]Lancaster J. BAD apoptosis pathway expression and survival from cancer. Gynecologic Oncology 2011; 120(1): S24.
[13]Pareja F, Macleod D, Shu C, Crary JF, Canoll PD, Ross AH, et al. PI3K and Bcl-2 inhibition primes glioblastoma cells to apoptosis through downregulation of Mcl-1 and Phospho-BAD. Molecular Cancer Research Mcr 2014; 12(7): 987-1001.
[14]Ozgen N, Obreztchikova M, Guo J, Elouardighi H, Dorn GW, Wilson BA, et al. Protein kinase D links Gq-coupled receptors to cAMP response element-binding protein (CREB)-Ser133 phosphorylation in the heart. Journal of biological chemistry 2008; 283(25): 17009-17019.
[15]Johannessen M, Delghandi MP, Rykx A, Dragset M, Vandenheede JR, Van Lint J, et al. Protein kinase D induces transcription through direct phosphorylation of the cAMP-response element-binding protein. Journal of biological chemistry 2007; 282(20): 14777-14787.
[16]Ghosh I, Campbell ST, Carlson KJ, Buchholz CJ, Helmers MR. Mapping the BH3 Binding Interface of Bcl-xL, Bcl-2, and Mcl-1 using Split-Luciferase Reassembly. Biochemistry 2015.
[17]Yang Y, Huang F, Ren Y, Xing L, Wu Y, Li Z, et al. The anticancer effects of sodium selenite and selenomethionine on human colorectal carcinoma cell lines in nude mice. Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics 2009; 18(1): 1-8.
[18]Zgheib NB, Xiong Y, Marchion D, Ramirez I, Bush S, Lancaster PLJ, et al. BCL2 antagonist of cell death (BAD) gene sequence and functional analysis of phosphorylation sites in ovarian cancer. Gynecologic Oncology 2014; 133: 88.
[19]Ngok SP, Rory G, Antonis K, Peter S, Anastasiadis PZ. Phosphorylation-mediated 14-3-3 protein binding regulates the function of the rho-specific guanine nucleotide exchange factor (RhoGEF) Syx. Journal of Biological Chemistry 2013; 288(9): 6640-6650.
[20]Toruno C. Interdependence of Bad and Puma during ionizing-radiation-induced apoptosis. Plos One 2014; 9(2): e88151-e88151.
[21]Ugarte-Uribe B, García-Sáez AJ. Membranes in motion: mitochondrial dynamics and their role in apoptosis. Biological Chemistry 2014; 395(3): 297-311.
[22]Shi Y, Nikulenkov F, Zawacka-Pankau J, Li H, Gabdoulline R, Xu J, et al. ROS-dependent activation of JNK converts p53 into an efficient inhibitor of oncogenes leading to robust apoptosis. Cell Death & Differentiation 2014.
[23]Park K-W, Kundu J, Chae I-G, Kim D-H, Yu M-H, Kundu JK, et al. Carnosol induces apoptosis through generation of ROS and inactivation of STAT3 signaling in human colon cancer HCT116 cells. International Journal of Oncology 2014.
[24]Maillet A, Yadav S, Loo Y, Sachaphibulkij K, Pervaiz S. A novel Osmium-based compound targets the mitochondria and triggers ROS-dependent apoptosis in colon carcinoma. Cell death & disease 2013; 4(6): e653.
[25]Luo H, Yang Y, Huang F, Li F, Jiang Q, Shi K, et al. Selenite induces apoptosis in colorectal cancer cells via AKT-mediated inhibition of β-catenin survival axis. Cancer letters 2012; 315(1): 78-85.
[26]Nagy A, Eder K, Selak MA, Kalman B. Mitochondrial energy metabolism and apoptosis regulation in glioblastoma. Brain Research 2015; 1595c: 127–142.
[27]Watkins JL, Lewandowski KT, Meek SEM, Peter S, Alex T, Helen PW. Phosphorylation of the Par-1 polarity kinase by protein kinase D regulates 14-3-3 binding and membrane association. Proceedings of the National Academy of Sciences 2008; 105(47): 18378-18383.
[28]Xie Q, Huang Z, Liu Y, Liu X, Huang L. [Mitochondrial estrogen receptor β inhibits non-small cell lung cancer cell apoptosis via interaction with Bad]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 2015; 35(1): 98-102.
[29]Yao A, Shen Y, Wang A, Chen S, Zhang H, Chen F, et al. Sulforaphane induces apoptosis in adipocytes via Akt/p70s6k1/Bad inhibition and ERK activation. Biochemical & Biophysical Research Communications 2015.
[30]Zaika AI. Bacterial Pathogen Helicobacter pylori: A Bad AKT or Inhibits p53 Protein Activity. Digestive Diseases & Sciences 2015; 60(4): 1-2.
[31]Sastry KS, Al-Muftah MA, Li P, Al-Kowari MK, Wang E, Ismail CA, et al. Targeting proapoptotic protein BAD inhibits survival and self-renewal of cancer stem cells. Cell Death & Differentiation 2014; 21(12): 1936-1949.
[32]Jiang Q, Li F, Shi K, Wu P, An J, Yang Y, et al. ATF4 activation by the p38MAPK–eIF4E axis mediates apoptosis and autophagy induced by selenite in Jurkat cells. FEBS letters 2013; 587(15): 2420-2429.
[33]Wu P, Shi K, An J, Ci Y, Li F, Hui K, et al. The LEF1/CYLD axis and cIAPs regulate RIP1 deubiquitination and trigger apoptosis in selenite-treated colorectal cancer cells. Cell death & disease 2014; 5(2): e1085.
[34]Lan A, Xu W, Zhang H, Hua X, Zheng D, Guo R, et al. Inhibition of ROS-Activated p38MAPK pathway is involved in the protective effect of H2S against chemical hypoxia-induced inflammation in PC12 Cells. Neurochemical research 2013; 38(7): 1454-1466.
[1]Davis CD. Selenium supplementation and cancer prevention. Current Nutrition Reports 2012; 1(1): 16-23.
[2]Riaz M, Mehmood KT. SELENIUM IN HUMAN HEALTH AND DISEASE: A REVIEW. JPMI: Journal of Postgraduate Medical Institute 2012; 26(2).
[3]Sanmartín C, Plano D, Sharma AK, Palop JA. Selenium compounds, apoptosis and other types of cell death: an overview for cancer therapy. International journal of molecular sciences 2012; 13(8): 9649-9672.
[4]Rayman MP. Selenium and human health. The Lancet 2012; 379(9822): 1256-1268.
[5]Hui K, Yang Y, Shi K, Luo H, Duan J, An J, et al. The p38 MAPK-regulated PKD1/CREB/Bcl-2 pathway contributes to selenite-induced colorectal cancer cell apoptosis in vitro and in vivo. Cancer letters 2014; 354(1): 189-199.
[6]Luo H, Yang Y, Duan J, Wu P, Jiang Q, Xu C. PTEN-regulated AKT/FoxO3a/Bim signaling contributes to reactive oxygen species-mediated apoptosis in selenite-treated colorectal cancer cells. Cell death & disease 2013; 4(2): e481.
[7]Wu P, Shi KJ, An JJ, Ci YL, Li F, Hui KY, et al. The LEF1/CYLD axis and cIAPs regulate RIP1 deubiquitination and trigger apoptosis in selenite-treated colorectal cancer cells. Cell Death Dis 2014; 5: e1085.
[8]Shi K, Jiang Q, Li Z, Shan L, Li F, An J, et al. Sodium selenite alters microtubule assembly and induces apoptosis in vitro and in vivo. J Hematol Oncol 2013; 6(7).
[9]Shi K, An J, Shan L, Jiang Q, Li F, Ci Y, et al. Survivin-2B promotes autophagy by accumulating IKK alpha in the nucleus of selenite-treated NB4 cells. Cell Death Dis 2014; 5: e1071.
[10]An J, Shi K, Wei W, Hua F, Ci Y, Jiang Q, et al. The ROS/JNK/ATF2 pathway mediates selenite-induced leukemia NB4 cell cycle arrest and apoptosis in vitro and in vivo. Cell death & disease 2013; 4(12): e973.
[11]SF P, CY L, MJ H, SC T, DH K, FA C, et al. Curcumin-loaded nanoparticles enhance apoptotic cell death of U2OS human osteosarcoma cells through the Akt-Bad signaling pathway. International Journal of Oncology 2014; 44(1): 238-246.
[12]Lancaster J. BAD apoptosis pathway expression and survival from cancer. Gynecologic Oncology 2011; 120(1): S24.
[13]Pareja F, Macleod D, Shu C, Crary JF, Canoll PD, Ross AH, et al. PI3K and Bcl-2 inhibition primes glioblastoma cells to apoptosis through downregulation of Mcl-1 and Phospho-BAD. Molecular Cancer Research Mcr 2014; 12(7): 987-1001.
[14]Ozgen N, Obreztchikova M, Guo J, Elouardighi H, Dorn GW, Wilson BA, et al. Protein kinase D links Gq-coupled receptors to cAMP response element-binding protein (CREB)-Ser133 phosphorylation in the heart. Journal of biological chemistry 2008; 283(25): 17009-17019.
[15]Johannessen M, Delghandi MP, Rykx A, Dragset M, Vandenheede JR, Van Lint J, et al. Protein kinase D induces transcription through direct phosphorylation of the cAMP-response element-binding protein. Journal of biological chemistry 2007; 282(20): 14777-14787.
[16]Ghosh I, Campbell ST, Carlson KJ, Buchholz CJ, Helmers MR. Mapping the BH3 Binding Interface of Bcl-xL, Bcl-2, and Mcl-1 using Split-Luciferase Reassembly. Biochemistry 2015.
[17]Yang Y, Huang F, Ren Y, Xing L, Wu Y, Li Z, et al. The anticancer effects of sodium selenite and selenomethionine on human colorectal carcinoma cell lines in nude mice. Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics 2009; 18(1): 1-8.
[18]Zgheib NB, Xiong Y, Marchion D, Ramirez I, Bush S, Lancaster PLJ, et al. BCL2 antagonist of cell death (BAD) gene sequence and functional analysis of phosphorylation sites in ovarian cancer. Gynecologic Oncology 2014; 133: 88.
[19]Ngok SP, Rory G, Antonis K, Peter S, Anastasiadis PZ. Phosphorylation-mediated 14-3-3 protein binding regulates the function of the rho-specific guanine nucleotide exchange factor (RhoGEF) Syx. Journal of Biological Chemistry 2013; 288(9): 6640-6650.
[20]Toruno C. Interdependence of Bad and Puma during ionizing-radiation-induced apoptosis. Plos One 2014; 9(2): e88151-e88151.
[21]Ugarte-Uribe B, García-Sáez AJ. Membranes in motion: mitochondrial dynamics and their role in apoptosis. Biological Chemistry 2014; 395(3): 297-311.
[22]Shi Y, Nikulenkov F, Zawacka-Pankau J, Li H, Gabdoulline R, Xu J, et al. ROS-dependent activation of JNK converts p53 into an efficient inhibitor of oncogenes leading to robust apoptosis. Cell Death & Differentiation 2014.
[23]Park K-W, Kundu J, Chae I-G, Kim D-H, Yu M-H, Kundu JK, et al. Carnosol induces apoptosis through generation of ROS and inactivation of STAT3 signaling in human colon cancer HCT116 cells. International Journal of Oncology 2014.
[24]Maillet A, Yadav S, Loo Y, Sachaphibulkij K, Pervaiz S. A novel Osmium-based compound targets the mitochondria and triggers ROS-dependent apoptosis in colon carcinoma. Cell death & disease 2013; 4(6): e653.
[25]Luo H, Yang Y, Huang F, Li F, Jiang Q, Shi K, et al. Selenite induces apoptosis in colorectal cancer cells via AKT-mediated inhibition of β-catenin survival axis. Cancer letters 2012; 315(1): 78-85.
[26]Nagy A, Eder K, Selak MA, Kalman B. Mitochondrial energy metabolism and apoptosis regulation in glioblastoma. Brain Research 2015; 1595c: 127–142.
[27]Watkins JL, Lewandowski KT, Meek SEM, Peter S, Alex T, Helen PW. Phosphorylation of the Par-1 polarity kinase by protein kinase D regulates 14-3-3 binding and membrane association. Proceedings of the National Academy of Sciences 2008; 105(47): 18378-18383.
[28]Xie Q, Huang Z, Liu Y, Liu X, Huang L. [Mitochondrial estrogen receptor β inhibits non-small cell lung cancer cell apoptosis via interaction with Bad]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 2015; 35(1): 98-102.
[29]Yao A, Shen Y, Wang A, Chen S, Zhang H, Chen F, et al. Sulforaphane induces apoptosis in adipocytes via Akt/p70s6k1/Bad inhibition and ERK activation. Biochemical & Biophysical Research Communications 2015.
[30]Zaika AI. Bacterial Pathogen Helicobacter pylori: A Bad AKT or Inhibits p53 Protein Activity. Digestive Diseases & Sciences 2015; 60(4): 1-2.
[31]Sastry KS, Al-Muftah MA, Li P, Al-Kowari MK, Wang E, Ismail CA, et al. Targeting proapoptotic protein BAD inhibits survival and self-renewal of cancer stem cells. Cell Death & Differentiation 2014; 21(12): 1936-1949.
[32]Jiang Q, Li F, Shi K, Wu P, An J, Yang Y, et al. ATF4 activation by the p38MAPK–eIF4E axis mediates apoptosis and autophagy induced by selenite in Jurkat cells. FEBS letters 2013; 587(15): 2420-2429.
[33]Wu P, Shi K, An J, Ci Y, Li F, Hui K, et al. The LEF1/CYLD axis and cIAPs regulate RIP1 deubiquitination and trigger apoptosis in selenite-treated colorectal cancer cells. Cell death & disease 2014; 5(2): e1085.
[34]Lan A, Xu W, Zhang H, Hua X, Zheng D, Guo R, et al. Inhibition of ROS-Activated p38MAPK pathway is involved in the protective effect of H2S against chemical hypoxia-induced inflammation in PC12 Cells. Neurochemical research 2013; 38(7): 1454-1466.