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Withanolide D of Ashwagandha improves Apoptosis in the Bone Marrow of Leukemic Murine Model

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Open Access
Article Type Research Article
Subject Medicine Group
OCLC 9124592881
Sayantan Ghosh and Sujata Law*
Issue: Volume2-Issue6
Pages: 431-438
Received: 2021-05-19
Accepted: 2021-06-01
Published: 2021-06-02

Abstract

Background: Leukemia is one of the most occurring haematological pathologies in the world which develops due to the impairment in the hematopoietic machinery. Cellular death via apoptosis is severely impaired in this pathophysiological condition and leads to the progression of the disease.
Objective: We have tried to unearth the efficacy of Withanolide D, a steroidal lactone derived from Withania somnifera or Ashwagandha on some of the apoptotic machinery components, i.e. TERT, BCL2 and PUMA in the experimental leukemic mice.

Materials and Methods: LD50 and EC50 values of Withanolide D were estimated. Three groups of animals were taken for experimental purpose i.e. Group I = Leukemic, (L); Group II = Control, (C); Group III = Leukemic treated with Withanolide D, (L + WD). Group III received Withanolide D via oral route and other two groups received equal volume of distilled water. Various cytological, immunofluorescence and flow cytometric studies were taken into consideration post administration.

Result: Leukemic group showed increased cellular proliferation and decreased cellular death as compared to control. Post Withanolide D administration TERT, BCL2 and PUMA expression started to shift towards normal status. This shift in the expressional values of increased apoptosis rate and decreased cellular proliferation revealed by cytological, immunofluorescence studies and flow cytometric investigations.

Conclusion: As Withanolide D decreased the suppression of apoptosis and impaired the progression of the disease, so, we can conclude that Withanolide D of Ashwagandha may hold a promise towards a new therapeutic strategy in leukemia.

FullText HTML FullText PDF DOI: 10.37871/jbres1255 Crossmark

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Copyright

© 2021 Law S, et al. Distributed under Creative Commons CC-BY 4.0 Creative CommonsAttribution

How to cite this article

Sayantan G, Sujata L. Withanolide D of Ashwagandha improves Apoptosis in the Bone Marrow of Leukemic Murine Model. J Biomed Res Environ Sci. 2021 June 02; 2(6): 431-438. doi: 10.37871/jbres1255, Article ID: jbres1255

Subject area(s)

HematologyBlood Disorders

References

  1. Law S, Maiti D, Palit A, Majumder D, Basu K, Chaudhuri S, Chaudhuri S. Facilitation of functional compartmentalization of bone marrow cells in leukemic mice by biological response modifiers: an immunotherapeutic approach. Immunol Lett. 2001 Apr 2;76(3):145-52. doi: 10.1016/s0165-2478(00)00317-5. PMID: 11306141.
  2. Law S, Begum B, Chaudhuri S. Pluripotent bone marrow cells in leukemic mice elicit enhanced immune reactivity following sheep erythrocyte administration in-vivo. A possible S-LFA3 interactive immunotherapy. J Exp Clin Cancer Res. 2003 Jun;22(2):213-21. PMID: 12866571.
  3. Sujata L, Chaudhuri S. Stem cell niche, the microenvironment and immunological crosstalk. Cell Mol Immunol. 2008 Apr;5(2):107-12. doi: 10.1038/cmi.2008.13. PMID: 18445340; PMCID: PMC4651246.
  4. Law S, Chaudhuri S. Stem cell niche failure concerns bone marrow failure--a diagnostic and therapeutic consideration. J Stem Cells. 2011;6(2):67-73. PMID: 22997847.
  5. Henrich CJ, Brooks AD, Erickson KL, Thomas CL, Bokesch HR, Tewary P, Thompson CR, Pompei RJ, Gustafson KR, McMahon JB, Sayers TJ. Withanolide E sensitizes renal carcinoma cells to TRAIL-induced apoptosis by increasing cFLIP degradation. Cell Death Dis. 2015 Feb 26;6(2):e1666. doi: 10.1038/cddis.2015.38. PMID: 25719250; PMCID: PMC4669816.
  6. Issa ME, Wijeratne EMK, Gunatilaka AAL, Cuendet M. Withanolide D Exhibits Similar Cytostatic Effect in Drug-Resistant and Drug-Sensitive Multiple Myeloma Cells. Front Pharmacol. 2017 Sep 8;8:610. doi: 10.3389/fphar.2017.00610. PMID: 28943850; PMCID: PMC5596074.
  7. Ichikawa H, Takada Y, Shishodia S, Jayaprakasam B, Nair MG, Aggarwal BB. Withanolides potentiate apoptosis, inhibit invasion, and abolish osteoclastogenesis through suppression of nuclear factor-kappaB (NF-kappaB) activation and NF-kappaB-regulated gene expression. Mol Cancer Ther. 2006 Jun;5(6):1434-45. doi: 10.1158/1535-7163.MCT-06-0096. PMID: 16818501.
  8. Lacombe J, Cretignier T, Meli L, Wijeratne EMK, Veuthey JL, Cuendet M, Gunatilaka AAL, Zenhausern F. Withanolide D Enhances Radiosensitivity of Human Cancer Cells by Inhibiting DNA Damage Non-homologous End Joining Repair Pathway. Front Oncol. 2020 Jan 8;9:1468. doi: 10.3389/fonc.2019.01468. PMID: 31970089; PMCID: PMC6960174.
  9. Wijeratne EMK, Oliveira MCF, Mafezoli J, Xu YM, Minguzzi S, Batista PHJ, Pessoa ODL, Whitesell L, Gunatilaka AAL (2018) Withaferin A and Withanolide D Analogues with Dual Heat-Shock-Inducing and Cytotoxic Activities: Semisynthesis and Biological Evaluation. Journal of Natural Products, 81(4), 825–837.
  10. https://doi.org/10.1021/acs.jnatprod.7b00918
  11. Ruvolo PP, Deng X, May WS. Phosphorylation of Bcl2 and regulation of apoptosis. Leukemia. 2001 Apr;15(4):515-22. doi: 10.1038/sj.leu.2402090. PMID: 11368354.
  12. Zinkel S, Gross A, Yang E. BCL2 family in DNA damage and cell cycle control. Cell Death Differ. 2006 Aug;13(8):1351-9. doi: 10.1038/sj.cdd.4401987. Epub 2006 Jun 9. PMID: 16763616.
  13. Coxon A, Rieu P, Barkalow FJ, Askari S, Sharpe AH, von Andrian UH, Arnaout MA, Mayadas TN. A novel role for the beta 2 integrin CD11b/CD18 in neutrophil apoptosis: a homeostatic mechanism in inflammation. Immunity. 1996 Dec;5(6):653-66. doi: 10.1016/s1074-7613(00)80278-2. PMID: 8986723.
  14. Ding Y, Yang Z, Zhang W, Xu Y, Wang Y, Hu M, Ma F, Long H, Tao N, Qin Z. Eugenol triggers BCL2 + Gr1 + myeloid-derived suppressor cell apoptosis via endogenous apoptosis pathway. RSC Advances. 2018; 8(7): 3833-3838. doi: 10.1039/C7RA13499A
  15. El Kebir D, József L, Pan W, Filep JG. Myeloperoxidase delays neutrophil apoptosis through CD11b/CD18 integrins and prolongs inflammation. Circ Res. 2008 Aug 15;103(4):352-9. doi: 10.1161/01.RES.0000326772.76822.7a. Epub 2008 Jul 10. PMID: 18617697.
  16. Graf M, Reif S, Kröll T, Hecht K, Nuessler V, Schmetzer H. Expression of MAC-1 (CD11b) in acute myeloid leukemia (AML) is associated with an unfavorable prognosis. Am J Hematol. 2006 Apr;81(4):227-35. doi: 10.1002/ajh.20526. PMID: 16550517.
  17. Xu S, Li X, Zhang J, Chen J. Prognostic Value of BCL2 Expression Level for Acute Myeloid Leukemia Patients: A Meta-Analysis. PLOS ONE. 2015;10(8): e0135981. doi: 10.1371/journal.pone.0135981
  18. Guirguis AA, Slape CI, Failla LM, Saw J, Tremblay CS, Powell DR, Rossello F, Wei A, Strasser A, Curtis DJ. PUMA promotes apoptosis of hematopoietic progenitors driving leukemic progression in a mouse model of myelodysplasia. Cell Death Differ. 2016 Jun;23(6):1049-59. doi: 10.1038/cdd.2015.159. Epub 2016 Jan 8. PMID: 26742432; PMCID: PMC4987724.
  19. Guirguis AA, Slape CI, Failla LM, Saw J, Tremblay CS, Powell DR, Rossello F, Wei A, Strasser A, Curtis DJ. PUMA promotes apoptosis of hematopoietic progenitors driving leukemic progression in a mouse model of myelodysplasia. Cell Death Differ. 2016 Jun;23(6):1049-59. doi: 10.1038/cdd.2015.159. Epub 2016 Jan 8. PMID: 26742432; PMCID: PMC4987724.
  20. Zhang F, Li Y, Tang Z, Kumar A, Lee C, Zhang L, Zhu C, Klotzsche-von Ameln A, Wang B, Gao Z, Zhang S, Langer HF, Hou X, Jensen L, Ma W, Wong W, Chavakis T, Liu Y, Cao Y, Li X. Proliferative and survival effects of PUMA promote angiogenesis. Cell Rep. 2012 Nov 29;2(5):1272-85. doi: 10.1016/j.celrep.2012.09.023. Epub 2012 Nov 1. PMID: 23122957.
  21. Zhang LN, Li JY, Xu W. A review of the role of Puma, Noxa and Bim in the tumorigenesis, therapy and drug resistance of chronic lymphocytic leukemia. Cancer Gene Ther. 2013 Jan;20(1):1-7. doi: 10.1038/cgt.2012.84. Epub 2012 Nov 23. PMID: 23175245.
  22. Vinayagamurthy S, Ganguly A, Chowdhury S. Extra-telomeric impact of telomeres: Emerging molecular connections in pluripotency or stemness. J Biol Chem. 2020 Jul 24;295(30):10245-10254. doi: 10.1074/jbc.REV119.009710. Epub 2020 May 22. PMID: 32444498; PMCID: PMC7383370.
  23. Mattson MP, Zhang P, Fu W. Roles for TERT and Telomerase in Cell Differentiation and Apoptosis. 17.
  24. Shen Y, Xi F, Li H, Luo Y, Chen C, Wang L. Telomerase reverse transcriptase suppression inhibits cell proliferation and promotes cell apoptosis in hepatocellular cancer. IUBMB Life. 2018 Jul;70(7):642-648. doi: 10.1002/iub.1758. Epub 2018 Apr 29. PMID: 29707886.
  25. Druckrey H, Preussmann R, Ivankovic S, Schmähl D. Organotrope carcinogene Wirkungen bei 65 verschiedenen N-Nitroso-Verbindungen an BD-Ratten [Organotropic carcinogenic effects of 65 various N-nitroso- compounds on BD rats]. Z Krebsforsch. 1967;69(2):103-201. German. PMID: 4230610.
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