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Mistarz A, Graczyk M, Winkler M, et al. Induction of cell death in ovarian cancer cells by doxorubicin and oncolytic vaccinia virus is associated with CREB3L1 activation. Mol Ther Oncolytics. 2021;23:38-50doi: 10.1016/j.omto.2021.04.014.
Mistarz, A., Graczyk, M., Winkler, M., Singh, P. K., Cortes, E., Miliotto, A., Liu, S., Long, M., Yan, L., Stablewski, A., O'Loughlin, K., Minderman, H., Odunsi, K., Rokita, H., McGray, A. J. R., Zsiros, E., & Kozbor, D. (2021). Induction of cell death in ovarian cancer cells by doxorubicin and oncolytic vaccinia virus is associated with CREB3L1 activation. Molecular therapy oncolytics, 2338-50. https://doi.org/10.1016/j.omto.2021.04.014
Mistarz, Anna, et al. "Induction of cell death in ovarian cancer cells by doxorubicin and oncolytic vaccinia virus is associated with CREB3L1 activation." Molecular therapy oncolytics vol. 23 (2021): 38-50. doi: https://doi.org/10.1016/j.omto.2021.04.014
Mistarz A, Graczyk M, Winkler M, Singh PK, Cortes E, Miliotto A, Liu S, Long M, Yan L, Stablewski A, O'Loughlin K, Minderman H, Odunsi K, Rokita H, McGray AJR, Zsiros E, Kozbor D. Induction of cell death in ovarian cancer cells by doxorubicin and oncolytic vaccinia virus is associated with CREB3L1 activation. Mol Ther Oncolytics. 2021 Apr 29;23:38-50. doi: 10.1016/j.omto.2021.04.014. eCollection 2021 Dec 17. PMID: 34632049; PMCID: PMC8479291.
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Mol Ther Oncolytics. 2021 Apr 29;23:38-50. doi: 10.1016/j.omto.2021.04.014. eCollection 2021 Dec 17.

Induction of cell death in ovarian cancer cells by doxorubicin and oncolytic vaccinia virus is associated with CREB3L1 activation.

Molecular therapy oncolytics

Anna Mistarz, Matthew Graczyk, Marta Winkler, Prashant K Singh, Eduardo Cortes, Anthony Miliotto, Song Liu, Mark Long, Li Yan, Aimee Stablewski, Kieran O'Loughlin, Hans Minderman, Kunle Odunsi, Hanna Rokita, A J Robert McGray, Emese Zsiros, Danuta Kozbor

Affiliations

  1. Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
  2. Center for Personalized Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
  3. Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
  4. Department of Gynecologic Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
  5. Department of Molecular and Cellular Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
  6. Department of Flow and Image Cytometry, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
  7. Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Kraków, Poland.

PMID: 34632049 PMCID: PMC8479291 DOI: 10.1016/j.omto.2021.04.014

Abstract

We have demonstrated that oncolytic vaccinia virus synergizes with doxorubicin (DOX) in inducing immunogenic cell death in platinum-resistant ovarian cancer cells and increases survival in syngeneic and xenograft tumor models. However, the mechanisms underlying the virus- and doxorubicin-mediated cancer cell death remain unknown. In this study, we investigated the effect of the oncolytic virus and doxorubicin used alone or in combination on activation of the cytoplasmic transcription factor CREB3L1 (cyclic AMP [cAMP] response element-binding protein 3-like 1) in ovarian cancer cell lines and clinical specimens. We demonstrated that doxorubicin-mediated cell death in ovarian cancer cell lines was associated with nuclear translocation of CREB3L1 and that the effect was augmented by infection with oncolytic vaccinia virus or treatment with recombinant interferon (IFN)-β used as a viral surrogate. This combination treatment was also effective in mediating nuclear translocation of CREB3L1 in cancer cells isolated from ovarian tumor biopsies at different stages of disease progression. The measurement of CREB3L1 expression in clinical specimens of ovarian cancer revealed lack of correlation with the stage of disease progression, suggesting that understanding the mechanisms of nuclear accumulation of CREB3L1 after doxorubicin treatment alone or in combination with oncolytic virotherapy may lead to the development of more effective treatment strategies against ovarian cancer.

© 2021 The Authors.

Keywords: CREB3L1; IFN-β; doxorubicin; oncolytic vaccinia virus; ovarian cancer

Conflict of interest statement

The authors declare no competing interests.

References

  1. Virus Res. 2011 Sep;160(1-2):40-50 - PubMed
  2. Nat Immunol. 2010 Nov;11(11):997-1004 - PubMed
  3. Br J Cancer. 2016 Jan 19;114(2):177-87 - PubMed
  4. Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7544-9 - PubMed
  5. Mol Cell Biol. 2013 Dec;33(24):4985-95 - PubMed
  6. J Biol Chem. 2020 Jul 24;295(30):10271-10280 - PubMed
  7. Oncogene. 2019 Apr;38(15):2814-2829 - PubMed
  8. J Immunol. 2014 Nov 15;193(10):5327-37 - PubMed
  9. Lancet Oncol. 2008 Jun;9(6):533-42 - PubMed
  10. Cell. 2007 Nov 16;131(4):660-8 - PubMed
  11. J Intern Med. 2010 May;267(5):526-42 - PubMed
  12. Ann Oncol. 2017 Apr 1;28(4):711-717 - PubMed
  13. PLoS One. 2015 Jun 25;10(6):e0129233 - PubMed
  14. Cancer Res. 2001 Dec 15;61(24):8751-7 - PubMed
  15. Nat Med. 2014 Nov;20(11):1301-9 - PubMed
  16. Front Immunol. 2017 May 15;8:555 - PubMed
  17. Virology. 1995 Jan 10;206(1):136-47 - PubMed
  18. J Cell Biol. 1993 May;121(3):521-41 - PubMed
  19. Cell. 2011 Mar 4;144(5):646-74 - PubMed
  20. J Immunother Cancer. 2019 Jan 9;7(1):6 - PubMed
  21. Brain Res Mol Brain Res. 1999 May 21;69(1):93-103 - PubMed
  22. Mol Ther. 2013 Nov;21(11):2074-86 - PubMed
  23. Cancer. 2019 Dec 15;125 Suppl 24:4582-4586 - PubMed
  24. Proc Natl Acad Sci U S A. 2013 Apr 2;110(14):E1291-300 - PubMed
  25. Biol Cell. 2011 Jul;103(7):319-31 - PubMed
  26. Cytometry A. 2011 Jun;79(6):461-9 - PubMed
  27. Semin Oncol Nurs. 2019 Apr;35(2):151-156 - PubMed
  28. Am J Reprod Immunol. 2008 Jan;59(1):62-74 - PubMed
  29. BMC Cancer. 2018 Aug 13;18(1):813 - PubMed
  30. Nat Rev Cancer. 2014 Aug;14(8):559-67 - PubMed
  31. Nat Commun. 2017 Oct 20;8(1):1079 - PubMed
  32. Mol Ther Oncolytics. 2016 Dec 14;3:16034 - PubMed
  33. Cardiology. 2010;115(2):155-62 - PubMed
  34. J Immunol. 2018 Jan 15;200(2):450-458 - PubMed
  35. J Immunol Methods. 2015 Aug;423:3-11 - PubMed
  36. Breast Cancer Res Treat. 2016 Apr;156(3):597-606 - PubMed
  37. Cell Death Differ. 2012 Dec;19(12):1939-49 - PubMed
  38. Breast Cancer Res. 2016 Jan 25;18(1):12 - PubMed
  39. J Neuroinflammation. 2018 Jul 6;15(1):199 - PubMed
  40. Elife. 2012 Dec 18;1:e00090 - PubMed
  41. Cancer Res. 2005 Nov 1;65(21):9991-8 - PubMed
  42. Cold Spring Harb Protoc. 2016 Nov 1;2016(11): - PubMed
  43. Clin Exp Immunol. 2006 Nov;146(2):344-53 - PubMed
  44. Methods. 2001 Dec;25(4):402-8 - PubMed
  45. Cold Spring Harb Protoc. 2016 Nov 1;2016(11): - PubMed
  46. J Drug Deliv. 2013;2013:898146 - PubMed
  47. Cancer Immun. 2007 Dec 21;7:21 - PubMed
  48. Epigenetics. 2014 Dec;9(12):1626-40 - PubMed
  49. Sci Rep. 2015 Nov 30;5:17228 - PubMed
  50. Cell Host Microbe. 2011 Jul 21;10(1):65-74 - PubMed
  51. Oncology (Williston Park). 2013 Apr;27(4):288-94, 298 - PubMed
  52. J Cancer. 2019 Jun 9;10(15):3517-3525 - PubMed
  53. JAMA Oncol. 2017 Jun 1;3(6):841-849 - PubMed
  54. Mol Ther Oncolytics. 2018 Mar 22;9:13-21 - PubMed
  55. Trends Immunol. 2015 Apr;36(4):250-6 - PubMed

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