DOI QR코드

DOI QR Code

Autophagy inhibition through PI3K/Akt increases apoptosis by sodium selenite in NB4 cells

  • Ren, Yun (National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Science, Chinese Academy of Medical Sciences and Peking Union Medical College) ;
  • Huang, Fang (National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Science, Chinese Academy of Medical Sciences and Peking Union Medical College) ;
  • Liu, Yuan (National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Science, Chinese Academy of Medical Sciences and Peking Union Medical College) ;
  • Yang, Yang (National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Science, Chinese Academy of Medical Sciences and Peking Union Medical College) ;
  • Jiang, Qian (National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Science, Chinese Academy of Medical Sciences and Peking Union Medical College) ;
  • Xu, Caimin (National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Science, Chinese Academy of Medical Sciences and Peking Union Medical College)
  • Published : 2009.09.30

Abstract

Selenium possesses the chemotherapeutic feature by inducing apoptosis in cancer cell with trivial side effects on normal cells. However, the mechanism in which is not clearly understood. Emerging evidence indicates the overlaps between the autophagy and the apoptosis. In this study, we have investigated the role of autophagy in selenium-induced apoptosis in NB4 cells. We find that autophagy is suppressed in NB4 cells treated by sodium selenite, as measured by electron microscope, acridine orange staining and western blot. Moreover, selenite combined with autophagy inhibitor contributes to the up-regulation of apoptosis, while the PI3K/Akt signaling pathway is down- regulated. Consistently, when the inhibitor of PI3K was applied, the autophagic level significantly decreased. In summary, sodium selenite increases NB4 cell apoptosis by autophagy inhibition through PI3K/Akt, and the inhibition of autophagy contributes to the up-regulation of apoptosis.

References

  1. Mizushima, N. (2007) Autophagy: process and function. Genes & Development. 21, 2871-2873
  2. Klionsky, D. J. (2007) Autophagy: from phenomenology to molecular understanding in less than a decade. Nat. Rev. Mol. Cell Bio. 8, 931-937 https://doi.org/10.1038/nrm2245
  3. Maiuri, M. C., Zalckvar, E., Kimchi, A. and Kroemer, G. (2007) Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat. Rev. Mol. Cell Bio. 8, 741-950 https://doi.org/10.1038/nrm2239
  4. Lee, J. A., Gao, F. B. (2008) ESCRT, autophagy, and frontotemporal dementia. BMB Rep. 41, 827-832 https://doi.org/10.5483/BMBRep.2008.41.12.827
  5. Dourmashkin, L. R., Allen, P. D., Gray, A. B., Newland, A. C. and Kelsey, S. M. (1997) Inhibition of autophagy abrogates tumour necrosis factor α induced apoptosis in human T-lymphoblastic leukaemic cells. Br. J. Haematol. 98, 673-685 https://doi.org/10.1046/j.1365-2141.1997.2623081.x
  6. Klein, E. A. (2004) Selenium: epidemiology and basic science. J. Urol. 171, S50-53 https://doi.org/10.1097/01.ju.0000107837.66277.e9
  7. Nelson, M. A., Reid, M., Duffield-Lillico, A. J. and Marshall, J. R. (2002). Prostate cancer and selenium. Urol. Clin. North. Am. 29, 67-70 https://doi.org/10.1016/S0094-0143(02)00018-6
  8. Rayman, M. P. (2005) Selenium in cancer prevention: a review of the evidence and mechanism of action. Proc. Nutr. Soc. 64, 527-542 https://doi.org/10.1079/PNS2005467
  9. Asfour, I. A., Eshazly, S., Fayek, M. H., Hegab, H. M., Raouf, S. and Moussa, M. A. (2006) Effect of high-dose sodium selenite therapy on polymorphonuclear leukocyte apoptosis in non-Hodgkin's lymphoma patients. Biol. Trace. Elem. Res. 110, 19-32 https://doi.org/10.1385/BTER:110:1:19
  10. Li, J., Zuo, L., Shen, T., Xu, C. M. and Zhang, Z. N. (2003) Induction of apoptosis by sodium selenite in human acute promyelelocytic leukemia NB4 cells: Involvement of oxidative stress and mitochondria. J. Trace. Elem. Med. Bio. 7, 19-26
  11. Marte, B. M. and Downward, J. (1997) PKB/Akt: connecting phosphoinositide 3-kinase to cell survival and beyond. Trends Biochem. Sci. 22, 355-358 https://doi.org/10.1016/S0968-0004(97)01097-9
  12. Kang, H. Y., Shiim, D., Kang, S. S., Chang, S. I. and Kim, H. Y. (2006) Protein kinase B inhibits endostatin-induced apoptosis in HUVECs. J. Biochem. Mol. Biol. 39, 97-104 https://doi.org/10.5483/BMBRep.2006.39.1.097
  13. Han, B., Wei, W., Hua, F., Cao, T., Dong, H., Yang, T., Yang, Y., Pan, H. and Xu, C. (2007) Requirement for ERK activity in sodium selenite-induced apoptosis of acute promyelocytic leukemia-derived NB4 cells. J. Biochem. Mol. Biol. 40, 196-204 https://doi.org/10.5483/BMBRep.2007.40.2.196
  14. Hennessy, B. T., Smith, D. L. and Ram, P. T. (2005) Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat. Rev. Drug. Discov. 4, 988-1004 https://doi.org/10.1038/nrd1902
  15. Zeng, X. and Kinsella, T. J. (2008) Mammalian target of Rapamycin and S6 Kinase 1 positively regulate 6-thioguanine-induced autophagy. Cancer Res. 68, 2384-2390 https://doi.org/10.1158/0008-5472.CAN-07-6163
  16. Guan, L., Han, B., Li, Z., Hua, F., Huang, F., Wei, W., Yang, Y. and Xu, C. (2009) Sodium selenite induces apoptosis by ROS-mediated endoplasmic reticulum stress and mitochondrial dysfunction in human acute promyelocytic leukemia NB4 cells. Apoptosis. 14, 218-225 https://doi.org/10.1007/s10495-008-0295-5
  17. Bursch, W. (2001) The autophagosomal-lysosomal compartment in programmed cell death. Cell Death Differ. 8, 569-581 https://doi.org/10.1038/sj.cdd.4400852
  18. Seglen, P. O. and Gordon, P. B. (1982) 3-Methyladenine: specific inhibitor of autophagic/lysosomal protein degradation in isolated rat hepatocytes. Proc. Natl. Acad. Sci. U.S.A. 79, 1889-1892 https://doi.org/10.1073/pnas.79.6.1889
  19. Bowman, E. J., Siebers, A. and Altendorf, K. (1988) Bafilomycins: a class of inhibitors of membrane ATPases from microorganisms, animal cells, and plant cells. Proc. Natl. Acad. Sci. U.S.A 85, 7972-7976 https://doi.org/10.1073/pnas.85.21.7972
  20. Cui, Q., Tashiro, S., Onodera, S. and Ikejima, T. (2006) Augmentation of oridonin-induced apoptosis observed with reduced autophagy. J. Pharmacol. Sci. 101, 230-239 https://doi.org/10.1254/jphs.FPJ06003X
  21. Klionsky, D. J., Meijer, A. J. and Codogno, P. (2005) Autophagy and p70S6 kinase. Autophagy 1, 59-60 https://doi.org/10.4161/auto.1.1.1536
  22. Petiot, A., Ogier-Denis, E., Blommaart, E. F., Meijer, A. J. and Codogno, P. (2000) Distinct classes of phosphatidylinositol 3'-kinases are involved in signaling pathways that control macroautophagy in HT-29 cells. J. Biol. Chem. 275, 992-998 https://doi.org/10.1074/jbc.275.2.992
  23. Arico, S., Petiot, A., Bauvy, C., Dubbelhuis, P. F., Meijer, A. J., Codogno, P. and Ogier-Denis, E. (2001). The tumorsuppressor PTEN positively regulates macroautophagy by inhibiting the phosphatidylinositol 3-kinase/protein kinase B pathway. J. Biol. Chem. 276, 35243-35246 https://doi.org/10.1074/jbc.C100319200
  24. Degenhardt, K., Mathew, R., Beaudoin, B., Bray, K., Anderson, D., Chen, G., Mukherjee, C., Shi, Y., Gelinas, C., Fan, Y., Nelson, D. A., Jin, S. and White, E. (2006). Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. Cancer Cell 10, 51-64 https://doi.org/10.1016/j.ccr.2006.06.001
  25. Lemasters, J. J., Nieminen, A. L., Qian, T., Trost, L. C., Elmore, S. P., Nishimura, Y., Crowe, R. A., Cascio, W. E., Bradham, C. A., Brenner, D. A. and Herman, B. (1998). The mitochondrial permeability transition in cell death: a common mechanism in necrosis, apoptosis and autophagy. Biochim. Biophys. Acta. 1366, 177-196 https://doi.org/10.1016/S0005-2728(98)00112-1
  26. Amaravadi, R. K., Yu, D., Lum, J. J., Bui, T., Christophorou, M. A., Evan, G. I., Thomas-Tikhonenko, A. and Thompson, C. B. (2007). Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of lymphoma. J. Clin. Invest. 117, 326-336 https://doi.org/10.1172/JCI28833
  27. Boya, P., Gonzalez-Polo, R. A., Casares, N., Perfettini, J. L., Dessen, P., Larochette, N., Metivier, D., Meley, D., Souquere, S., Yoshimori, T., Pierron, G., Codogno, P. and Kroemer, G. (2004). Inhibition of Macroautophagy Triggers Apoptosis. MCB 25, 1025-1040 https://doi.org/10.1128/MCB.25.3.1025-1040.2005

Cited by

  1. Autophagy inhibitor 3-methyladenine potentiates apoptosis induced by dietary tocotrienols in breast cancer cells vol.54, pp.2, 2015, https://doi.org/10.1007/s00394-014-0707-y
  2. Selenium Cytotoxicity in Cancer vol.114, pp.5, 2014, https://doi.org/10.1111/bcpt.12207
  3. Spermidine may decrease ER stress in pancreatic beta cells and may reduce apoptosis via activating AMPK dependent autophagy pathway vol.77, pp.4, 2011, https://doi.org/10.1016/j.mehy.2011.07.014
  4. Selenate inhibits adipogenesis through induction of transforming growth factor-β1 (TGF-β1) signaling vol.426, pp.4, 2012, https://doi.org/10.1016/j.bbrc.2012.08.125
  5. C<sub>16</sub> Saturated Fatty Acid Induced Autophagy in A549 Cells through Topoisomerase I Inhibition vol.03, pp.09, 2012, https://doi.org/10.4236/fns.2012.39160
  6. The Combination ofα-Tocopheryl Succinate and Sodium Selenite on Breast Cancer: A Merit or a Demerit? vol.2016, 2016, https://doi.org/10.1155/2016/4741694
  7. TGF-β1 Protects against Mesangial Cell Apoptosis via Induction of Autophagy vol.285, pp.48, 2010, https://doi.org/10.1074/jbc.M109.093724
  8. Methylseleninic Acid Suppresses Pancreatic Cancer Growth Involving Multiple Pathways vol.66, pp.2, 2014, https://doi.org/10.1080/01635581.2014.868911
  9. Autophagy Influences Maternal mRNA Degradation and Apoptosis in Porcine Parthenotes Developing In Vitro vol.58, pp.5, 2012, https://doi.org/10.1262/jrd.2012-005
  10. Autophagy and chemotherapy resistance: a promising therapeutic target for cancer treatment vol.4, pp.10, 2013, https://doi.org/10.1038/cddis.2013.350
  11. Sequential Release of Autophagy Inhibitor and Chemotherapeutic Drug with Polymeric Delivery System for Oral Squamous Cell Carcinoma Therapy vol.11, pp.5, 2014, https://doi.org/10.1021/mp5000423
  12. Selenium protects against cadmium-induced kidney apoptosis in chickens by activating the PI3K/AKT/Bcl-2 signaling pathway vol.24, pp.25, 2017, https://doi.org/10.1007/s11356-017-9422-6
  13. Inhibition of autophagy promotes caspase-mediated apoptosis by tunicamycin in HepG2 cells vol.24, pp.9, 2014, https://doi.org/10.3109/15376516.2014.956915
  14. Insulin on activation of autophagy with integrins and syndecans against MPP + -induced α-synuclein neurotoxicity vol.633, 2016, https://doi.org/10.1016/j.neulet.2016.09.023
  15. The Selenium Metabolite Methylselenol Regulates the Expression of Ligands That Trigger Immune Activation through the Lymphocyte Receptor NKG2D vol.289, pp.45, 2014, https://doi.org/10.1074/jbc.M114.591537
  16. Sodium Selenite-Induced Apoptosis Mediated by ROS Attack in Human Osteosarcoma U2OS Cells vol.145, pp.1, 2012, https://doi.org/10.1007/s12011-011-9154-2
  17. Progress in the unraveling of the endoplasmic reticulum stress/autophagy pathway and cancer: Implications for future therapeutic approaches vol.13, pp.3, 2010, https://doi.org/10.1016/j.drup.2010.04.002
  18. Selenite-induced apoptosis and autophagy in colon cancer cells vol.26, pp.2, 2012, https://doi.org/10.1016/j.tiv.2011.12.010
  19. Role of autophagy in the progression and suppression of leukemias vol.81, pp.3, 2012, https://doi.org/10.1016/j.critrevonc.2011.03.009
  20. Apoptosis and Autophagy in Cold Preservation Ischemia vol.91, pp.11, 2011, https://doi.org/10.1097/TP.0b013e31821ab9c8
  21. Selenite targets eIF4E-binding protein-1 to inhibit translation initiation and induce the assembly of non-canonical stress granules vol.40, pp.16, 2012, https://doi.org/10.1093/nar/gks566
  22. ROS inhibit autophagy by downregulating ULK1 mediated by the phosphorylation of p53 in selenite-treated NB4 cells vol.5, pp.11, 2014, https://doi.org/10.1038/cddis.2014.506
  23. The role of nitric oxide and autophagy in liver injuries induced by selenium deficiency in chickens vol.5, pp.62, 2015, https://doi.org/10.1039/C5RA01030F
  24. Knockdown of AKT3 and PI3KCA by RNA interference changes the expression of the genes that are related to apoptosis and autophagy in T98G glioblastoma multiforme cells vol.67, pp.6, 2015, https://doi.org/10.1016/j.pharep.2015.04.012
  25. Survivin-2B promotes autophagy by accumulating IKK alpha in the nucleus of selenite-treated NB4 cells vol.5, pp.2, 2014, https://doi.org/10.1038/cddis.2014.34
  26. Omeprazole Inhibits Proliferation and Modulates Autophagy in Pancreatic Cancer Cells vol.6, pp.5, 2011, https://doi.org/10.1371/journal.pone.0020143
  27. Elevation of protective autophagy as a potential way for preventing developmental neurotoxicity of general anesthetics vol.82, pp.2, 2014, https://doi.org/10.1016/j.mehy.2013.11.032
  28. Regulatory Coordination between Two Major Intracellular Homeostatic Systems vol.288, pp.21, 2013, https://doi.org/10.1074/jbc.M113.462408
  29. Modulation of Imatinib Cytotoxicity by Selenite in HCT116 Colorectal Cancer Cells vol.116, pp.1, 2015, https://doi.org/10.1111/bcpt.12281
  30. Thapsigargin induces apoptosis when autophagy is inhibited in HepG2 cells and both processes are regulated by ROS-dependent pathway vol.41, 2016, https://doi.org/10.1016/j.etap.2015.11.020
  31. Combination Therapy with AKT3 and PI3KCA siRNA Enhances the Antitumor Effect of Temozolomide and Carmustine in T98G Glioblastoma Multiforme Cells vol.30, pp.2, 2016, https://doi.org/10.1007/s40259-016-0160-y
  32. Combination of N-(4-hydroxyphenyl) retinamide and apigenin suppressed starvation-induced autophagy and promoted apoptosis in malignant neuroblastoma cells vol.502, pp.1, 2011, https://doi.org/10.1016/j.neulet.2011.07.016
  33. The combination of rapamycin and MAPK inhibitors enhances the growth inhibitory effect on Nara-H cells vol.33, pp.6, 2014, https://doi.org/10.3892/ijmm.2014.1715
  34. Knockdown of autophagy-related protein 6, Beclin-1, decreases cell growth, invasion, and metastasis and has a positive effect on chemotherapy-induced cytotoxicity in osteosarcoma cells vol.36, pp.4, 2015, https://doi.org/10.1007/s13277-014-2868-y
  35. Induction of apoptosis and autophagy by sodium selenite in A549 human lung carcinoma cells through generation of reactive oxygen species vol.212, pp.3, 2012, https://doi.org/10.1016/j.toxlet.2012.06.007
  36. Selenite-induced autophagy antagonizes apoptosis in colorectal cancer cells in vitro and in vivo vol.35, pp.3, 2016, https://doi.org/10.3892/or.2015.4484
  37. Dietary Antioxidants: Potential Anticancer Agents vol.69, pp.4, 2017, https://doi.org/10.1080/01635581.2017.1299872
  38. Selenium Compounds, Apoptosis and Other Types of Cell Death: An Overview for Cancer Therapy vol.13, pp.12, 2012, https://doi.org/10.3390/ijms13089649
  39. Selenium compounds as therapeutic agents in cancer vol.1850, pp.8, 2015, https://doi.org/10.1016/j.bbagen.2014.10.008
  40. Selenite induces DNA damage and specific mitochondrial degeneration in human bladder cancer cells vol.32, 2016, https://doi.org/10.1016/j.tiv.2015.12.011
  41. Apoptosis and antitumor effects induced by the combination of an mTOR inhibitor and an autophagy inhibitor in human osteosarcoma MG63 cells vol.48, pp.1, 2016, https://doi.org/10.3892/ijo.2015.3227
  42. Insulin suppresses MPP+-induced neurotoxicity by targeting integrins and syndecans in C6 astrocytes 2017, https://doi.org/10.1080/10799893.2017.1369119
  43. Hsp90 inhibitor induces autophagy and apoptosis in osteosarcoma cells vol.46, pp.1, 2015, https://doi.org/10.3892/ijo.2014.2727
  44. Rapamycin suppresses ROS-dependent apoptosis caused by selenomethionine in A549 lung carcinoma cells vol.67, pp.5, 2011, https://doi.org/10.1007/s00280-010-1417-7
  45. Effects of 17-DMAG Administration on Autophagy Flux in Mouse Skeletal Muscle vol.26, pp.4, 2016, https://doi.org/10.5352/JLS.2016.26.4.387
  46. microRNA-206 is required for osteoarthritis development through its effect on apoptosis and autophagy of articular chondrocytes via modulating the phosphoinositide 3-kinase/protein kinase B-mTOR pathway by targeting insulin-like growth factor-1 pp.07302312, 2018, https://doi.org/10.1002/jcb.27803
  47. Selenium deficiency induces splenic growth retardation by deactivating the IGF-1R/PI3K/Akt/mTOR pathway pp.1756-591X, 2018, https://doi.org/10.1039/C8MT00183A