Skip to main content
SpringerLink
Log in

Evaluation of Anti-Proprotein Convertase Activity of Diterpene Andrographolid Derived Products

  • Chapter
Regulation of Carcinogenesis, Angiogenesis and Metastasis by the Proprotein Convertases (PCs)

Abstract

SEA, a mixture of succinoyl ester derivatives of andrographolid, previously shown to be the first in vitro nonpeptide inhibitor of Proprotein Convertases (PC) PC1, furin, and PC7 [Basak, et al., Biochem. J. 1999; 338: 107–113] has been tested ex vivo for its anti-Proprotein Convertase (PC) activity. SEA blocks PC-mediated cleavages of proBDNF (Brain Derived Neurotrophic Factor) (RVRR128↓HS) and surface envelope glycoprotein gp160 of HIV (RERR511↓AV) in a dose dependent manner. 25 μM of SEA completely blocks the cleavage of 32 kDa proBDNF into its 14 kDa mature form while 75 μM prevents significantly HIV gp160 processing into gp41. The estimated IC50 value for the latter is ∼ 40 μM. At higher concentration, SEA is partly cytotoxic to the cells, with less protein secretion in culture medium. In an effort to examine further, the anti-PC activity of SEA and other andrographolid products, we examined their effects on human leukemic cell growth. Data showed a 15–50% decrease in growth in presence of SEA depending on the concentration used. These findings may provide a rationale for designing nonpeptide inhibitors of PCs based on androgholide molecule present in abundance in the medicinally active plant Andrographis paniculata (AP)

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Chrètien M, Li CH (1967) Isolation, purification and characterization of c lipotropic hormpone from sheep pituitary glands. Can. J. Biochem. 45:1163–1174

    Article  PubMed  Google Scholar 

  2. Steiner DF, Cunningham D, Spiegelman L, Aten B (1967) Insulin biosynthesis: Evidence for a precursor. Science. 157:697–699

    Article  PubMed  CAS  Google Scholar 

  3. Deadman J (2000) Proteinase inhibitors and activators strategic targets for therapeutic intervention. J. Pept. Sci. 6:421–431

    Article  PubMed  CAS  Google Scholar 

  4. Southan C (2000) Assessing the protease and protease inhibitor content of the human genome. ‘‘Proteinase inhibitors and activators: Strategic targets for therapeutic intervention’’, University of Oxford, 17–20

    Google Scholar 

  5. Behrens G, Dejam A, Schmidt H, Balks HJ, Brabant G, Korner T, Stoll M, Schmidt RE (1999) Impaired glucose tolerance, beta cell function and lipid metabolism in HIV patients under treatment with protease inhibitors. AIDS. 13:F63–F70. (Also see: http://www.hhs.gov/news/press/2004pres/ 20040516a.html and http://www.thebody.com/treat/newdrugs.html.

    Article  PubMed  CAS  Google Scholar 

  6. Mikolajczyk1 SD, Millar LS, Marker KM, Rittenhouse HG, Wolfert RL, Marks LS, Charlesworth MC, Tindall DJ (1999) Identification of a Novel Complex between Human Kallikrein 2 and Protease Inhibitor-6 in Prostate Cancer Tissue. Cancer Research 59:3927–3930

    Google Scholar 

  7. Song XY, Zeng L, Jin W, Thompson J, Mizel DE, Lei KJ, Billinghurst RC, Poole RA, Wahl SM (1999) Secretory Leukocyte Protease Inhibitor Suppresses the Inflammation and Joint Damage of Bacterial Cell Wall–induced Arthritis. Exp Med 190:535–542. (Also see http://www.arrivapharm.com/product-copd.php)

    Article  CAS  Google Scholar 

  8. Seidah NG, Chrètien M (1999) Proprotein and prohprmone convertases: A family of subtilases generating diverse bioactive polypeptides. Brain Research 848:45–62

    Article  PubMed  CAS  Google Scholar 

  9. Steiner DF (1998) The proprotein Convertases. Curr Opin Chem Biol 2:31–39

    Article  PubMed  CAS  Google Scholar 

  10. Thomas G (2002) Furin at the cutting edge: from protein traffic to embryogenesis and disease. Nat Rev Mol Cell Biol 3:753–766

    Article  PubMed  CAS  Google Scholar 

  11. Sarac MS, Peinado JR, Leppla SH, Lindberg I (2004) Protection against anthrax toxemia by hexa-D-arginine in vitro and in vivo. Infect Immun. 72:602–605

    Article  PubMed  CAS  Google Scholar 

  12. Jean F, Thomas L, Molloy SS, Liu G, Jarvis MA, Nelson JA, Thomas G (2000) A protein-based therapeutic for human cytomegalovirus infection. Proc Nat Acad Sci USA 97:2864–2869

    Article  PubMed  CAS  Google Scholar 

  13. Feldmann H, Volchkov VE, Volchkova VA, Klenk HD (1999) The glycoproteins of Marburg and Ebola virus and their potential roles in pathogenesis. Arch Virol Suppl 15:159–169

    PubMed  CAS  Google Scholar 

  14. Zambon MC (2001) The pathogenesis of influenza in humans. Rev Med Virol 11:227–241

    Article  PubMed  CAS  Google Scholar 

  15. Fugere M, Day R (2002) Inhibitors of the subtilase-like pro-protein convertases (SPCs). Curr Pharm Des 8:549–562

    Article  PubMed  CAS  Google Scholar 

  16. Basak, A (2005) Proprotein Convertase inhibitors: Minireview. J. Mol. Med. 83:844–855

    Article  PubMed  CAS  Google Scholar 

  17. Bassi DE, Mahloogi H, Lopez De Cicco R, Klein-Szanto A (2003) Increased furin activity enhances the malignant phenotype of human head and neck cancer cells. Am J Pathol 62:439–447

    Google Scholar 

  18. Khatib AM, Siegfried G, Prat A, Luis J, Chretien M, Metrakos P, Seidah NG (2001) Inhibition of proprotein convertases is associated with loss of growth and tumorigenicity of HT-29 human colon carcinoma cells: Importance of insulin-like growth factor-1 (IGF-1) receptor processing in IGF-1-mediated functions. J Biol Chem 276:30686–30693

    Article  PubMed  CAS  Google Scholar 

  19. Mowla SJ, Farhadi HF, Pareek S, Atwal JK, Morris SJ, Seidah NG, Murphy RA (2001) Biosynthesis and post-translational processing of the precursor to brain-derived neurotrophic factor. J Biol Chem 276:12660–12666

    Article  PubMed  CAS  Google Scholar 

  20. Tsuji A, Hashimoto E, Ikoma T, Taniguchi T, Mori K, Nagahama M, Matsuda Y (1999) Inactivation of proprotein convertase, PACE4, by alpha1-antitrypsin Portland (alpha1-PDX), a blocker of proteolytic activation of bone morphogenetic protein during embryogenesis: Evidence that PACE4 is able to form an SDS-stable acyl intermediate with alpha1-PDX. J Biochem (Tokyo). 126:591–603

    CAS  Google Scholar 

  21. Jean F, Basak A, DiMaio J, Seidah NG, Lazure C (1995) An internally quenched fluorogenic PC1 and furin substrate leads to a potent prohormone convertase inhibitor. Biochem J 307:689–695

    PubMed  CAS  Google Scholar 

  22. Basak A, Schmidt C, Ismail AA, Seidah NG, Chrètien M, Lazure C (1995) Peptidyl Substrates containing Unnatural amino acid at the P′ 1 positio are Potent Inhibitors of Prohormone Convertases. Int J Pept Prot Res 46:228–237

    Article  CAS  Google Scholar 

  23. Jean F, Boudreault A, Basak A, Seidah NG, Lazure C (1995) Fluorescent peptidyl substrates as an aid in studying the substrate specificity of human prohormone convertase PC1 and furin and in designing a potent irreversible inhibitor. J Biol Chem 270:19225–19231

    Article  PubMed  CAS  Google Scholar 

  24. Zhong M, Munzer JS, Basak A, Benjannet S, Mowla SJ, Decroly E, Chrètien M, Seidah NG (1999) The prosegments of Furin and PC7 as potent inhibitors of proprotein convertases: In vitro and ex vivo assessment of their specificity and selectivity. J Biol Chem 274:33913–33920

    Article  PubMed  CAS  Google Scholar 

  25. Basak A, Lazure C (2003) Synthetic peptides of prosegments of proprotein convertases PC1 and furin are inhibitors of both convertases with some selectivity. Biochem J 373:231–239

    Article  PubMed  CAS  Google Scholar 

  26. Basak A, Cooper S, Roberge AG, Banik UK, Chrètien M, Seidah NG (1999) Inhibition of proprotein convertases-1, -7 and furin by diterpines of Andrographis paniculata and their succinoyl esters. Biochem J 338:107–113

    Article  PubMed  CAS  Google Scholar 

  27. Chiou WF, Lin JJ, Chen CF (1998) Andrographolid suppresses the expression of inducible nitric oxide synthase in macrophage and restores the vasoconstriction in rat aorta treated with lipopolysaccharide. Br J Pharmacol 125:327–334

    Article  PubMed  CAS  Google Scholar 

  28. Handa SS, Sharma A (1990) Hepatoprotective activity of andrographolid from Andrographis paniculata against carbontetrachloride. Indian J Med Res 92:276–283

    PubMed  CAS  Google Scholar 

  29. Choudhury BR, Poddar MK (1984) Andrographolid and kalmegh (Andrographis paniculata) extract: in vivo and in vitro effect on hepatic lipid peroxidation. Methods Find Exp Clin Pharmacol 6:481–485

    PubMed  CAS  Google Scholar 

  30. Amroyan E, Gabrielian E, Panossian A, Wikman G, Wagner H (1999) Inhibitory effect of andrographolid from Andrographis paniculata on PAF-induced platelet aggregation. Phytomedicine, 6:27–31

    PubMed  CAS  Google Scholar 

  31. Visen PK, Shukla B, Patnaik GK, Dhawan BN (1993) Andrographolid protects rat hepatocytes against paracetamol-induced damage. J Ethnopharmacol 40:131–136

    Article  PubMed  CAS  Google Scholar 

  32. Shukla B, Visen PK, Patnaik GK, Dhawan BN (1992) Choleretic effect of andrographolid in rats and guinea pigs. Planta Med 58:146–149

    Article  PubMed  CAS  Google Scholar 

  33. Aminuddin A, Girach RD (1991) (Surv Medicinal Plants Unit, Regl Res Inst Unani Med, Bhadrak 756100). Ethnobotanical studies on Bondo tribe of district Koraput (Orissa), India. Ethnobotany 3 (1&2):15–19

    Google Scholar 

  34. Zhang CY, Tan BK (1997) Mechanisms of cardiovascular activity of Andrographis paniculata in the anaesthetized rat. J Ethnopharmacol 56:97–101

    Article  PubMed  CAS  Google Scholar 

  35. Puri A, Saxena R, Saxena RP, Saxena KC, Srivastava V, Tandon JS (1993) Immunostimulant agents from Andrographis paniculata. J Nat Product 56:995–999

    Article  CAS  Google Scholar 

  36. Choudhury BR, Poddar MK (1985) Andrographolid and kalmegh (Andrographis paniculata) extract: Effect on intestinal brush-border membrane-bound hydrolases. Methods Find Exp Clin Pharmacol 7:617–621

    PubMed  CAS  Google Scholar 

  37. Panossian A, Kochikian A, Gabrielian E, Muradian R, Stepanian H, Arsenian F, Wagner H (1999) Effect of Andrographis paniculata extract on progesterone in blood plasma of pregnant rats. Phytomedicine 6:157–161

    PubMed  CAS  Google Scholar 

  38. Kapil A, Koul IB, Banerjee SK, Gupta BD (1993) Antihepatotoxic effects of major diterpenoid constituents of Andrographis paniculata. Biochem Pharmacol 46:182–185

    Article  PubMed  CAS  Google Scholar 

  39. Choudhury BR, Haque SJ, Poddar MK (1987) In vivo and in vitro effects of kalmegh (Andrographis paniculata) extract and andrographolid on hepatic microsomal drug metabolizing enzymes. Planta Med. 53:135–140

    Article  PubMed  CAS  Google Scholar 

  40. Càceres DD, Hancke JL, Burgos RA, Sandberg F, Wikman GK (1999) Use of visual analogue scale measurements (VAS) to assess the effectiveness of standardized Andrographis paniculata extract SHA-10 in reducing the symptoms of common cold. A randomized double blind-placebo study. Phytomedicine 6:217–223

    Google Scholar 

  41. Matsuda T, Kuroyanagi M, Sugiyama S, Umehara K, Ueno A, Nishi K (1994) Cell differentiation-inducing diterpenes from Andrographis paniculata Nees. Chem Pharm Bull (Tokyo). 42:1216–1225

    CAS  Google Scholar 

  42. Mehrotra R, Rawat S, Kulshreshtha DK, Patnaik GK, Dhawan BN (1990) In vitro studies on the effect of certain natural products against hepatitis B virus. Indian J Med Res 92:133–138

    PubMed  CAS  Google Scholar 

  43. Chang RS, Ding L, Chen GQ, Pan QC, Zhao ZL, Smith KM (1991) Dehydroandrographolid succinic acid monoester as an inhibitor against the human immunodeficiency virus. Proc Soc Exp Biol Med 197:59–66

    PubMed  CAS  Google Scholar 

  44. Seidah NG, Benjannet S, Pareek S, Chretien M, Murphy RA (1996) Cellular processing of the neurotrophin precursors of NT3 and BDNF by the mammalian proprotein convertases. FEBS Lett 379:248–250

    Article  Google Scholar 

  45. Seidah NG, Benjannet S, Pareek S, Savaria D, Hamelin J, Goulet B, Lalibete J, Lazure C, Chretien M, Murphy RA (1996) Cellular processing of the nerve growth factor precursor by the mammalian pro-protein convertases. Biochem J 314:951–960

    PubMed  CAS  Google Scholar 

  46. Mowla SJ, Pareek S, Farhadi HF, Petrecca K, Fawcett JP, Seidah NG, Morris SJ, Sossin WS, Murphy RA (1999) Differential sorting of nerve growth factor and brain-derived neurotrophic factor in hippocampal neurons. J Neurosci 19:2069–2080

    PubMed  CAS  Google Scholar 

  47. Yan Q, Rosenfeld RD, Matheson CR, Hawkins N, Lopez OT, Bennett L, Welcher AA (1997) Expression of brain-derived neurotrophic factor protein in the adult rat central nervous system. Neuroscience 78:431–448

    Article  PubMed  CAS  Google Scholar 

  48. Wouters S, Decroly E, Vandenbranden M, Shober D, Fuchs R, Morel V, Leruth M, Seidah NG, Courtoy PJ, Ruysschaert JM (1999) Occurrence of an HIV-1 gp160 endoproteolytic activity in low-density vesicles and evidence for a distinct density distribution from endogenously expressed furin and PC7/LPC convertases. FEBS Lett 456:97–102

    Article  PubMed  CAS  Google Scholar 

  49. Vollenweider F, Benjannet S, Decroly E, Savaria D, Lazure C, Thomas G, Chretien M, Seidah NG (1996) Comparative cellular processing of the human immunodeficiency virus (HIV-1) envelope glycoprotein gp160 by the mammalian subtilisin/kexin-like convertases. Biochem J 314:521–532

    PubMed  CAS  Google Scholar 

  50. Pedersen JR, Olsson JO (2003) Soxhlet extraction of acrylamide from potato chips. Analyst 128:332–334

    Article  PubMed  CAS  Google Scholar 

  51. Basak A, Zhong M, Munzer JS, Chretien M, Seidah NG (2001) Implication of the proprotein convertases furin, PC5 and PC7 in the cleavage of surface glycoproteins of Hong Kong, Ebola and respiratory syncytial viruses: A comparative analysis with fluorogenic peptides. Biochem J 353:537–545

    Article  PubMed  CAS  Google Scholar 

  52. Basak A, Li S, Banik UK (2003) A new combination drugs using andrographolid derived natural product Restomune for management of HIV: A case study. Case Reports and Clinical Practice Review 4:223–233

    Google Scholar 

  53. Chang RS, Yeung HW (1988) Inhibition of growth of human immunodeficiency virus in vitro by crude extracts of Chinese medicinal herbs. Antiviral Research 9:163–176 (http://www.aids.org/atn/a-061-04.html)

    Article  PubMed  CAS  Google Scholar 

  54. Bassi DE, Lopez De Cicco R, Mahloogi H, Zucker S, Thomas G, Klein-Szanto AJ (2001) Furin inhibition results in absent or decreased invasiveness and tumorigenicity of human cancer cells. Proc Natl Acad Sci USA 98:10326–10331

    Article  PubMed  CAS  Google Scholar 

  55. (http://www.geocities.com/andrographis/AndroBaseText.txt)

    Google Scholar 

  56. Rajagopal S, Kumar RA, Deevi DS, Satyanarayana C, Rajagopalan R (2003) Andrographolide, a potential cancer therapeutic agent isolated from Andrographis paniculata. J Exp Ther Oncol 3:147–158

    Article  PubMed  CAS  Google Scholar 

  57. Matsuda T, Kuroyanagi M, Sugiyama S, Umehara K, Ueno A, Nishi K (1994) Cell differentiation-inducing diterpenes from Andrographis paniculata Nees. Chem Pharm Bull (Tokyo) 42:1216–1225

    CAS  Google Scholar 

  58. Lan MT, Sifzizul Muhammad TST, Kuroyanagi M, Sulaiman SF, Najimuddn N: Determination of growth inhibitory activities of several bioactive compounds of Andrographis paniculata a panel of human tumor cell lines: 14-deoxy-11, 12- didehydroandrographolid induces a non-apoptotic programmed cell death in T-47D, a breast carcinoma cell line. www.usm.my/nsf/sample{%}20full{%}20paper3-20Sept.pdf.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Diseases of Aging Program, Regional Protein Chemistry Center, Ottawa Health Research Institute, Loeb Building, 725 Parkdale Ave, Ottawa, ON K1Y 4K9

    Ajoy Basak

  2. Bioscan Continental Inc., 350, Industriel Boul., St-Eustache, Quebec J7R 5R4, Canada

    Upendra K. Banik & Suiyang Li

  3. Biochemical Neuroendocrinology laboratory, Clinical Research Institute of Montreal, 110 Pine Ave, W, Montrèal, Que H2W 1R7, Canada

    Nabil G. Seidah

Authors
  1. Ajoy Basak
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Upendra K. Banik
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sarmistha Basak
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nabil G. Seidah
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Suiyang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. INSERM, Paris, France

    A-Majid Khatib

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Springer

About this chapter

Cite this chapter

Basak, A., Banik, U.K., Basak, S., Seidah, N.G., Li, S. (2006). Evaluation of Anti-Proprotein Convertase Activity of Diterpene Andrographolid Derived Products. In: Khatib, AM. (eds) Regulation of Carcinogenesis, Angiogenesis and Metastasis by the Proprotein Convertases (PCs). Springer, Dordrecht. https://doi.org/10.1007/1-4020-5132-8_8

Download citation

Publish with us

Policies and ethics

Search

Navigation