Display options
Cite
Sarkar S, Jain S, Rai V, et al. Plant-derived SAC domain of PAR-4 (Prostate Apoptosis Response 4) exhibits growth inhibitory effects in prostate cancer cells. Front Plant Sci. 2015;6:822doi: 10.3389/fpls.2015.00822.
Sarkar, S., Jain, S., Rai, V., Sahoo, D. K., Raha, S., Suklabaidya, S., Senapati, S., Rangnekar, V. M., Maiti, I. B., & Dey, N. (2015). Plant-derived SAC domain of PAR-4 (Prostate Apoptosis Response 4) exhibits growth inhibitory effects in prostate cancer cells. Frontiers in plant science, 6822. https://doi.org/10.3389/fpls.2015.00822
Sarkar, Shayan, et al. "Plant-derived SAC domain of PAR-4 (Prostate Apoptosis Response 4) exhibits growth inhibitory effects in prostate cancer cells." Frontiers in plant science vol. 6 (2015): 822. doi: https://doi.org/10.3389/fpls.2015.00822
Sarkar S, Jain S, Rai V, Sahoo DK, Raha S, Suklabaidya S, Senapati S, Rangnekar VM, Maiti IB, Dey N. Plant-derived SAC domain of PAR-4 (Prostate Apoptosis Response 4) exhibits growth inhibitory effects in prostate cancer cells. Front Plant Sci. 2015 Oct 07;6:822. doi: 10.3389/fpls.2015.00822. eCollection 2015. PMID: 26500666; PMCID: PMC4595782.
Copy Download .nbib Format: NLM
Share it on

Front Plant Sci. 2015 Oct 07;6:822. doi: 10.3389/fpls.2015.00822. eCollection 2015.

Plant-derived SAC domain of PAR-4 (Prostate Apoptosis Response 4) exhibits growth inhibitory effects in prostate cancer cells.

Frontiers in plant science

Shayan Sarkar, Sumeet Jain, Vineeta Rai, Dipak K Sahoo, Sumita Raha, Sujit Suklabaidya, Shantibhusan Senapati, Vivek M Rangnekar, Indu B Maiti, Nrisingha Dey

Affiliations

  1. Department of Gene Function and Regulation, Institute of Life Sciences, Department of Biotechnology, Government of India Bhubaneswar, India.
  2. Department of Translational Research and Technology Development, Institute of Life Sciences, Department of Biotechnology, Government of India Bhubaneswar, India ; Manipal University Manipal, India.
  3. Kentucky Tobacco Research & Development Center, Plant Genetic Engineering Research and Services, College of Agriculture, Food and Environment, University of Kentucky, Lexington KY, USA ; Department of Agronomy, Iowa State University, Ames IA, USA.
  4. Department of Radiation Oncology, Feinberg School of Medicine, Northwestern University, Chicago IL, USA.
  5. Department of Translational Research and Technology Development, Institute of Life Sciences, Department of Biotechnology, Government of India Bhubaneswar, India.
  6. Department of Radiation Medicine, Markey Cancer Center, University of Kentucky, Lexington KY, USA.
  7. Kentucky Tobacco Research & Development Center, Plant Genetic Engineering Research and Services, College of Agriculture, Food and Environment, University of Kentucky, Lexington KY, USA.

PMID: 26500666 PMCID: PMC4595782 DOI: 10.3389/fpls.2015.00822

Abstract

The gene Par-4 (Prostate Apoptosis Response 4) was originally identified in prostate cancer cells undergoing apoptosis and its product Par-4 showed cancer specific pro-apoptotic activity. Particularly, the SAC domain of Par-4 (SAC-Par-4) selectively kills cancer cells leaving normal cells unaffected. The therapeutic significance of bioactive SAC-Par-4 is enormous in cancer biology; however, its large scale production is still a matter of concern. Here we report the production of SAC-Par-4-GFP fusion protein coupled to translational enhancer sequence (5' AMV) and apoplast signal peptide (aTP) in transgenic Nicotiana tabacum cv. Samsun NN plants under the control of a unique recombinant promoter M24. Transgene integration was confirmed by genomic DNA PCR, Southern and Northern blotting, Real-time PCR, and Nuclear run-on assays. Results of Western blot analysis and ELISA confirmed expression of recombinant SAC-Par-4-GFP protein and it was as high as 0.15% of total soluble protein. In addition, we found that targeting of plant recombinant SAC-Par-4-GFP to the apoplast and endoplasmic reticulum (ER) was essential for the stability of plant recombinant protein in comparison to the bacterial derived SAC-Par-4. Deglycosylation analysis demonstrated that ER-targeted SAC-Par-4-GFP-SEKDEL undergoes O-linked glycosylation unlike apoplast-targeted SAC-Par-4-GFP. Furthermore, various in vitro studies like mammalian cells proliferation assay (MTT), apoptosis induction assays, and NF-κB suppression suggested the cytotoxic and apoptotic properties of plant-derived SAC-Par-4-GFP against multiple prostate cancer cell lines. Additionally, pre-treatment of MAT-LyLu prostate cancer cells with purified SAC-Par-4-GFP significantly delayed the onset of tumor in a syngeneic rat prostate cancer model. Taken altogether, we proclaim that plant made SAC-Par-4 may become a useful alternate therapy for effectively alleviating cancer in the new era.

Keywords: SAC domain of Par-4; apoptosis; fusion protein; glycosylation; molecular farming; transgenic plant

References

  1. PLoS One. 2011;6(9):e24627 - PubMed
  2. Nat Protoc. 2006;1(5):2320-5 - PubMed
  3. Planta. 2014 Oct;240(4):855-75 - PubMed
  4. Plant Biotechnol J. 2009 Feb;7(2):183-99 - PubMed
  5. Plant Biotechnol J. 2005 May;3(3):309-18 - PubMed
  6. PLoS One. 2014 Jun 04;9(6):e98988 - PubMed
  7. Exp Cell Res. 2003 Feb 1;283(1):51-66 - PubMed
  8. J Cell Physiol. 2012 Dec;227(12):3715-21 - PubMed
  9. Mol Cell. 2005 Oct 7;20(1):33-44 - PubMed
  10. Biotechnol J. 2006 Oct;1(10):1071-9 - PubMed
  11. Mol Cell Biol. 2003 Aug;23(16):5516-25 - PubMed
  12. Plant Physiol. 2007 Aug;144(4):1843-51 - PubMed
  13. Molecules. 2015 May 07;20(5):8181-97 - PubMed
  14. Folia Biol (Praha). 2010;56(2):37-46 - PubMed
  15. Prostate. 2015 Jul 1;75(10):1020-33 - PubMed
  16. Cancer Res. 2007 Mar 1;67(5):1927-34 - PubMed
  17. Curr Genet. 2001 Apr;39(2):109-16 - PubMed
  18. Cancer Res. 2001 Oct 1;61(19):7255-63 - PubMed
  19. J Med Microbiol. 1996 Jun;44(6):453-63 - PubMed
  20. Transgenic Res. 2011 Apr;20(2):345-56 - PubMed
  21. Prostate Cancer Prostatic Dis. 2013 Mar;16(1):16-22 - PubMed
  22. Hematol J. 2001;2(2):103-7 - PubMed
  23. Cancer Biol Ther. 2008 Dec;7(12):1867-74 - PubMed
  24. Anticancer Res. 2004 Jan-Feb;24(1):91-100 - PubMed
  25. Science. 1992 Sep 11;257(5076):1496-502 - PubMed
  26. Plant Cell Rep. 2013 Nov;32(11):1771-82 - PubMed
  27. Trends Plant Sci. 2005 Dec;10(12):580-5 - PubMed
  28. Diabetes. 2001 Oct;50(10):2231-6 - PubMed
  29. J Biotechnol. 2014 Jan;169:103-11 - PubMed
  30. EMBO Rep. 2005 Jul;6(7):593-9 - PubMed
  31. J Virol Methods. 2009 Oct;161(1):114-21 - PubMed
  32. Curr Opin Biotechnol. 2007 Apr;18(2):134-41 - PubMed
  33. Res Commun Chem Pathol Pharmacol. 1993 Mar;79(3):293-312 - PubMed
  34. J Biol Chem. 2000 Mar 24;275(12):8610-7 - PubMed
  35. Nat Biotechnol. 2006 Oct;24(10):1191-3 - PubMed
  36. Plant Biotechnol J. 2008 Sep;6(7):633-48 - PubMed
  37. Plant Biotechnol J. 2006 Mar;4(2):169-81 - PubMed
  38. Cell. 2009 Jul 23;138(2):377-88 - PubMed
  39. Genome Res. 2013 Apr;23(4):581-91 - PubMed
  40. Proc Natl Acad Sci U S A. 2005 May 10;102(19):7026-30 - PubMed
  41. PLoS One. 2012;7(3):e31931 - PubMed
  42. Cell Death Differ. 2008 Sep;15(9):1460-71 - PubMed
  43. Cancer Biol Ther. 2011 Jul 15;12(2):152-7 - PubMed
  44. Transgenic Res. 2015 Apr;24(2):353-64 - PubMed
  45. Transgenic Res. 1999 Aug;8(4):255-63 - PubMed
  46. Mol Cell Biol. 1996 Dec;16(12):6945-56 - PubMed
  47. Int J Cancer. 2010 Dec 15;127(12):2893-917 - PubMed
  48. Plant J. 2000 Jun;22(6):543-51 - PubMed
  49. Ann N Y Acad Sci. 2007 Apr;1102:121-34 - PubMed
  50. Plant Physiol. 1995 Dec;109(4):1199-205 - PubMed
  51. QJM. 2004 Nov;97(11):705-16 - PubMed
  52. J Cell Biochem. 2004 Feb 15;91(3):504-12 - PubMed
  53. Proc Natl Acad Sci U S A. 2010 Jan 12;107(2):732-7 - PubMed
  54. Anal Biochem. 1976 May 7;72:248-54 - PubMed
  55. Plant Biotechnol J. 2008 Jun;6(5):504-15 - PubMed
  56. CA Cancer J Clin. 2014 Jan-Feb;64(1):9-29 - PubMed
  57. Oncogene. 1999 Feb 4;18(5):1205-8 - PubMed
  58. Plant Mol Biol. 1999 Jul;40(5):771-82 - PubMed
  59. Int J Oncol. 2005 Jan;26(1):159-67 - PubMed
  60. Cell Death Dis. 2015 Jul 02;6:e1804 - PubMed
  61. Br J Cancer. 2001 Nov 30;85(11):1801-8 - PubMed
  62. Gen Comp Endocrinol. 2008 Mar 1;156(1):63-70 - PubMed
  63. J Natl Cancer Inst. 2009 Jun 16;101(12):878-87 - PubMed
  64. Nat Protoc. 2006;1(6):3094-100 - PubMed
  65. Cell Growth Differ. 1994 Apr;5(4):457-66 - PubMed
  66. PLoS One. 2014 Feb 20;9(2):e89377 - PubMed

Publication Types

Grant support