DOI QR코드

DOI QR Code

Adenine Inhibits B16-F10 Melanoma Cell Proliferation

  • Silwal, Prashanta (Department of Biochemistry, College of Medicine, Chungnam National University) ;
  • Park, Seung-Kiel (Department of Biochemistry, College of Medicine, Chungnam National University)
  • Received : 2020.05.29
  • Accepted : 2020.07.24
  • Published : 2020.09.30

Abstract

Adenine, a purine base, is a structural component of essential biomolecules such as nucleic acids and adenine nucleotides. Its physiological roles have been uncovered. Adenine suppresses IgE-mediated allergy and LPS-induced inflammation. Although adenine is known to inhibit lymphocyte proliferation, the effect of adenine to melamoma cells is not reported. Here, we investigated the growth inhibitory effects of adenine on B16-F10 mouse melanoma cells. Adenine suppressed the proliferation of B16-F10 cells in dose-dependent manner with the maximal inhibitory dose of 2 mM. Adenine treatment induced cell death molecular markers such as PARP and caspase 3 cleavages. Pan-caspase inhibitor z-VAD dramatically rescued the cell death molecular markers, cell proliferation recovered marginally. These results provide the possibility of adenine to be used as an anti-tumor agent.

Keywords

References

  1. Avila MA, Garcia-Trevijano ER, Lu SC, Corrales FJ, Mato JM. Methylthioadenosine. Int J Biochem Cell Biol. 2004. 36: 2125-2130. Cheng YF, Young GH, Lin JT, Jang HH, Chen CC, Nong JY, https://doi.org/10.1016/j.biocel.2003.11.016
  2. Chen PK, Kuo CY, Kao SH, Liang YJ, Chen HM. Activation of AMP-Activated Protein Kinase by Adenine Alleviates TNF-Alpha-Induced Inflammation in Human Umbilical Vein Endothelial Cells. PLoS One. 2015.10: e0142283. https://doi.org/10.1371/journal.pone.0142283
  3. Cory S, Adams JM. The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer. 2002, 2: 647-656. https://doi.org/10.1038/nrc883
  4. Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007. 35: 495-516. https://doi.org/10.1080/01926230701320337
  5. Engle SJ, Stockelman MG, Chen J, Boivin G, Yum MN, Davies PM, Ying MY, Sahota A, Simmonds HA, Stambrook PJ, Tischfield JA. Adenine phosphoribosyltransferase-deficient mice develop 2,8-dihydroxyadenine nephrolithiasis. Proc Natl Acad Sci U S A. 1996. 93: 5307-5312. https://doi.org/10.1073/pnas.93.11.5307
  6. Gowans GJ, Hawley SA, Ross FA, Hardie DG. AMP is a true physiological regulator of AMP-activated protein kinase by both allosteric activation and enhancing net phosphorylation. Cell Metab. 2013.18: 556-566. https://doi.org/10.1016/j.cmet.2013.08.019
  7. Han M, Cheng X, Gao Z, Zhao R, Zhang S. Inhibition of tumor cell growth by adenine is mediated by apoptosis induction and cell cycle S phase arrest. Oncotarget. 2017. 8: 94286-94296. https://doi.org/10.18632/oncotarget.21690
  8. Hershfield MS, Snyder FF, Seegmiller JE. Adenine and adenosine are toxic to human lymphoblast mutants defective in purine salvage enzymes. Science. 1977. 197: 1284-1287. https://doi.org/10.1126/science.197600
  9. Kamatani N, Carson DA. Dependence of adenine production upon polyamine synthesis in cultured human lymphoblasts. Biochim Biophys Acta. 1981. 675: 344-350. https://doi.org/10.1016/0304-4165(81)90024-6
  10. Kaufmann SH, Desnoyers S, Ottaviano Y, Davidson NE, Poirier GG. Specific proteolytic cleavage of poly (ADP-ribose) polymerase: an early marker of chemotherapy-induced apoptosis. Cancer Res. 1993. 53: 3976-3985.
  11. Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972. 26: 239-257. https://doi.org/10.1038/bjc.1972.33
  12. Kishi T, Kittaka E, Hyodo S, Kashiwa H, Karakawa T, Suzawa T, Sakura N, Sakano T, Usui T. Inhibition by adenine of in vitro immunological functions of normal and adenine phosphoribosyltransferase-deficient human lymphocytes. Immunopharmacology. 1985. 10: 157-162. https://doi.org/10.1016/0162-3109(85)90021-9
  13. Lai HW, Wei JC, Hung HC, Lin CC. Adenine inhibits the growth of colon cancer cells via AMP-activated protein kinase mediated autophagy. Evid Based Complement Alternat Med. 2019. 2019: 9151070.
  14. Lowe SW, Lin AW. Apoptosis in cancer. Carcinogenesis. 2000. 21: 485-495 https://doi.org/10.1093/carcin/21.3.485
  15. Silwal P, Shin K, Choi S, Kang SW, Park JB, Lee HJ, Koo SJ, Chung KH, Namgung U, Lim K, Heo JY, Park JI, Park SK. Adenine suppresses IgE-mediated mast cell activation. Mol Immunol. 2015. 65: 242-249. https://doi.org/10.1016/j.molimm.2015.01.021
  16. Simon ER, Chapman RG, Finch CA. Adenine in red cell presservation. J Clin Invest. 1962. 41: 351-359. https://doi.org/10.1172/JCI104489
  17. Snyder FF, Hershfield MS, Seegmiller JE. Cytotoxic and metabolic effects of adenosine and adenine on human lymphoblasts. Cancer Res. 1978. 38: 2357-2362.
  18. Soengas MS, Lowe SW. Apoptosis and melanoma chemoresistance. Oncogene. 2003. 22: 3138-3151. https://doi.org/10.1038/sj.onc.1206454
  19. Su WW, Huang JY, Chen HM, Lin JT, Kao SH. Adenine inhibits growth of hepatocellular carcinoma cells via AMPK-mediated S phase arrest and apoptotic cascade. Int J Med Sci. 2020. 17: 678-684. https://doi.org/10.7150/ijms.42086
  20. Taylor RC, Cullen SP, Martin SJ. Apoptosis: controlled demolition at the cellular level. Nat Rev Mol Cell Biol. 2008. 9: 231-241. https://doi.org/10.1038/nrm2312
  21. Theodoropoulou S, Brodowska K, Kayama M, Morizane Y, Miller JW, Gragoudas ES, Vavvas DG. Aminoimidazole carboxamide ribonucleotide (AICAR) inhibits the growth of retinoblastoma in vivo by decreasing angiogenesis and inducing apoptosis. PLoS One. 2013. 8: e52852. https://doi.org/10.1371/journal.pone.0052852
  22. Thornberry NA. The caspase family of cysteine proteases. Br Med Bull. 1997. 53: 478-490. https://doi.org/10.1093/oxfordjournals.bmb.a011625
  23. Vincent EE, Coelho PP, Blagih J, Griss T, Viollet B, Jones RG. Differential effects of AMPK agonists on cell growth and metabolism. Oncogene. 2015. 34: 3627-3639. https://doi.org/10.1038/onc.2014.301
  24. Watanabe S, Yoshimi Y, Ikekita M. Neuroprotective effect of adenine on purkinje cell survival in rat cerebellar primary cultures. J Neurosci Res. 2003. 74: 754-759. https://doi.org/10.1002/jnr.10790
  25. Young GH, Lin JT, Cheng YF, Huang CF, Chao CY, Nong JY, Chen PK, Chen HM. Identification of adenine modulating AMPK activation in NIH/3T3 cells by proteomic approach. J Proteomics. 2015. 120: 204-214. https://doi.org/10.1016/j.jprot.2015.03.012
  26. Zadra G, Photopoulos C, Tyekucheva S, Heidari P, Weng QP, Fedele G, Liu H, Scaglia N, Priolo C, Sicinska E, Mahmood U, Signoretti S, Birnberg N, Loda M. A novel direct activator of AMPK inhibits prostate cancer growth by blocking lipogenesis. EMBO Mol Med. 2014. 6: 519-538. https://doi.org/10.1002/emmm.201302734