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Reddy D, Ghosh P, Kumavath R. Strophanthidin Attenuates MAPK, PI3K/AKT/mTOR, and Wnt/β-Catenin Signaling Pathways in Human Cancers. Front Oncol. 2020;9:1469doi: 10.3389/fonc.2019.01469.
Reddy, D., Ghosh, P., & Kumavath, R. (2019). Strophanthidin Attenuates MAPK, PI3K/AKT/mTOR, and Wnt/β-Catenin Signaling Pathways in Human Cancers. Frontiers in oncology, 91469. https://doi.org/10.3389/fonc.2019.01469
Reddy, Dhanasekhar, et al. "Strophanthidin Attenuates MAPK, PI3K/AKT/mTOR, and Wnt/β-Catenin Signaling Pathways in Human Cancers." Frontiers in oncology vol. 9 (2019): 1469. doi: https://doi.org/10.3389/fonc.2019.01469
Reddy D, Ghosh P, Kumavath R. Strophanthidin Attenuates MAPK, PI3K/AKT/mTOR, and Wnt/β-Catenin Signaling Pathways in Human Cancers. Front Oncol. 2020 Jan 17;9:1469. doi: 10.3389/fonc.2019.01469. eCollection 2019. PMID: 32010609; PMCID: PMC6978703.
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Front Oncol. 2020 Jan 17;9:1469. doi: 10.3389/fonc.2019.01469. eCollection 2019.

Strophanthidin Attenuates MAPK, PI3K/AKT/mTOR, and Wnt/β-Catenin Signaling Pathways in Human Cancers.

Frontiers in oncology

Dhanasekhar Reddy, Preetam Ghosh, Ranjith Kumavath

Affiliations

  1. Department of Genomic Science, School of Biological Sciences, Central University of Kerala, Kasaragod, India.
  2. Department of Computer Science, Virginia Commonwealth University, Richmond, VA, United States.

PMID: 32010609 PMCID: PMC6978703 DOI: 10.3389/fonc.2019.01469

Abstract

Lung cancer is the most prevalent in cancer-related deaths, while breast carcinoma is the second most dominant cancer in women, accounting for the most number of deaths worldwide. Cancers are heterogeneous diseases that consist of several subtypes based on the presence or absence of hormone receptors and human epidermal growth factor receptor 2. Several drugs have been developed targeting cancer biomarkers; nonetheless, their efficiency are not adequate due to the high reemergence rate of cancers and fundamental or acquired resistance toward such drugs, which leads to partial therapeutic possibilities. Recent studies on cardiac glycosides (CGs) positioned them as potent cytotoxic agents that target multiple pathways to initiate apoptosis and autophagic cell death in many cancers. In the present study, our aim is to identify the anticancer activity of a naturally available CG (strophanthidin) in human breast (MCF-7), lung (A549), and liver cancer (HepG2) cells. Our results demonstrate a dose-dependent cytotoxic effect of strophanthidin in MCF-7, A549, and HepG2 cells, which was further supported by DNA damage on drug treatment. Strophanthidin arrested the cell cycle at the G2/M phase; this effect was further validated by checking the inhibited expressions of checkpoint and cyclin-dependent kinases in strophanthidin-induced cells. Moreover, strophanthidin inhibited the expression of several key proteins such as MEK1, PI3K, AKT, mTOR, Gsk3α, and β-catenin from MAPK, PI3K/AKT/mTOR, and Wnt/β-catenin signaling. The current study adequately exhibits the role of strophanthidin in modulating the expression of various key proteins involved in cell cycle arrest, apoptosis, and autophagic cell death. Our

Copyright © 2020 Reddy, Ghosh and Kumavath.

Keywords: G2/M phase; Na+/K+-ATPase; apoptosis; autophagy; cardiac glycoside; strophanthidin

References

  1. J Neuroinflammation. 2007 Sep 04;4:21 - PubMed
  2. Cancers (Basel). 2019 Feb 14;11(2):null - PubMed
  3. J Biol Chem. 2005 Dec 16;280(50):41342-51 - PubMed
  4. World J Gastroenterol. 2008 Nov 7;14(41):6339-46 - PubMed
  5. Nat Protoc. 2006;1(1):23-9 - PubMed
  6. Mol Pharmacol. 2006 Feb;69(2):520-31 - PubMed
  7. Cancer Res. 2009 Aug 15;69(16):6556-64 - PubMed
  8. Oncogene. 2008 May 8;27(21):3010-20 - PubMed
  9. J Cell Physiol. 2017 Sep;232(9):2497-2507 - PubMed
  10. Oncotarget. 2018 Jan 11;9(34):23320-23333 - PubMed
  11. J Cancer. 2010 Sep 15;1:136-40 - PubMed
  12. Cancer Biol Ther. 2008 Jul;7(7):1033-6 - PubMed
  13. Nat Rev Genet. 2004 Sep;5(9):691-701 - PubMed
  14. Oncogene. 2000 Dec 27;19(56):6680-6 - PubMed
  15. Cancer Lett. 2019 Jul 1;453:57-73 - PubMed
  16. Oncogene. 2014 Apr 10;33(15):1890-903 - PubMed
  17. Recent Pat Anticancer Drug Discov. 2009 Jan;4(1):28-35 - PubMed
  18. Biochim Biophys Acta. 2007 Aug;1773(8):1263-84 - PubMed
  19. FEBS J. 2013 Jan;280(2):489-504 - PubMed
  20. Gut. 2018 Feb;67(2):348-361 - PubMed
  21. Oncol Lett. 2018 Apr;15(4):4463-4470 - PubMed
  22. Cancer Res. 2009 Apr 1;69(7):2739-47 - PubMed
  23. Proc Natl Acad Sci U S A. 2013 Dec 24;110(52):21124-9 - PubMed
  24. Molecules. 2016 Apr 22;21(4):534 - PubMed
  25. Cell Signal. 2002 Aug;14(8):649-54 - PubMed
  26. Onkologie. 2002 Dec;25(6):511-8 - PubMed
  27. Biochim Biophys Acta. 2010 Dec;1802(12):1237-45 - PubMed
  28. Neoplasia. 2007 Sep;9(9):766-76 - PubMed
  29. BMC Cancer. 2014 Aug 07;14:570 - PubMed
  30. Bioinformation. 2017 Sep 30;13(9):293-300 - PubMed
  31. Science. 2002 May 31;296(5573):1655-7 - PubMed
  32. Cold Spring Harb Perspect Biol. 2013 Apr 01;5(4):a008656 - PubMed
  33. Cell Signal. 2009 May;21(5):656-64 - PubMed
  34. Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13742-7 - PubMed
  35. Clin Cancer Res. 2001 May;7(5):1474-80 - PubMed
  36. Leukemia. 2012 May;26(5):1116-9 - PubMed
  37. Oncotarget. 2017 Feb 21;8(8):13085-13098 - PubMed
  38. Cell Signal. 2006 May;18(5):679-87 - PubMed
  39. Oncotarget. 2017 May 9;8(19):32043-32054 - PubMed
  40. Oncol Lett. 2014 Mar;7(3):815-819 - PubMed
  41. Adv Biol Regul. 2017 Aug;65:5-15 - PubMed
  42. Carcinogenesis. 2013 Aug;34(8):1870-80 - PubMed
  43. Front Immunol. 2017 Dec 18;8:1793 - PubMed
  44. CA Cancer J Clin. 2005 May-Jun;55(3):178-94 - PubMed
  45. Sci Rep. 2017 Apr 07;7:46134 - PubMed
  46. BMC Biol. 2004 May 18;2:7 - PubMed
  47. Cold Spring Harb Perspect Med. 2015 Apr 01;5(4):null - PubMed
  48. Cold Spring Harb Perspect Biol. 2012 Sep 01;4(9):a011189 - PubMed
  49. Molecules. 2017 Nov 08;22(11):null - PubMed
  50. Sci Rep. 2018 Jan 16;8(1):850 - PubMed
  51. Cancer Treat Rev. 2018 Jan;62:29-38 - PubMed
  52. Cancer Res. 2006 Jun 1;66(11):5867-74 - PubMed
  53. Trends Cell Biol. 2015 Sep;25(9):545-55 - PubMed
  54. N Engl J Med. 2008 Jan 31;358(5):502-11 - PubMed
  55. Biochim Biophys Acta. 2007 Aug;1773(8):1358-75 - PubMed
  56. Oncogene. 2008 Oct 20;27(48):6245-51 - PubMed
  57. Nat Rev Drug Discov. 2008 Nov;7(11):926-35 - PubMed
  58. Gene. 2001 Oct 17;277(1-2):15-30 - PubMed
  59. Front Pharmacol. 2018 Mar 01;9:70 - PubMed
  60. J Biol Chem. 2009 May 8;284(19):12772-82 - PubMed
  61. Nat Cell Biol. 2010 Aug;12(8):781-90 - PubMed
  62. Clin Cancer Res. 2008 Jun 15;14(12):3651-6 - PubMed
  63. Biochim Biophys Acta. 2007 Aug;1773(8):1213-26 - PubMed
  64. ACS Med Chem Lett. 2010 Jul 12;1(7):326-330 - PubMed
  65. Mol Interv. 2008 Feb;8(1):36-49 - PubMed
  66. Mitochondrion. 2013 May;13(3):225-34 - PubMed
  67. J Breast Cancer. 2016 Sep;19(3):231-241 - PubMed

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