World Journal of Microbiology and Biotechnology

, Volume 24, Issue 2, pp 189–195

Bioprospecting for antagonistic Penicillium strains as a resource of new antitumor compounds

  • Rosario Nicoletti
  • Elisabetta Buommino
  • Anna De Filippis
  • Maria Pilar Lopez-Gresa
  • Emiliano Manzo
  • Angela Carella
  • Marcella Petrazzuolo
  • Maria Antonietta Tufano
Original Paper

Abstract

Microorganisms are increasingly exploited as a source of new pharmaceuticals. Soil fungi are particularly promising to this regard since their biocenotic competitiveness is often based on the production of antibiotics and other inhibitory substances. About 15 Penicillium strains possessing some extent of antifungal ability were evaluated as a possible source of antitumor products based on the antiproliferative and pro-apoptotic effects of their culture extracts on human tumor cell lines. About 12 strains showed some extent of antitumor properties that in several cases corresponded to the effect of the extrolites purified from the culture extracts themselves. The study showed that a quick screening of fungal isolates can be operated by assaying their fungal extracts on tumor cells directly, with the ensuing advantage of restricting the work required for the characterization of the bioactive compounds to a reduced number of promising strains.

Keywords

Apoptosis Cell proliferation Cytostatic activity DNA laddering Extrolites Fungal extracts 

References

  1. Buommino E, Nicoletti R, Gaeta GM, Orlando M, Ciavatta ML, Baroni A, Tufano MA (2004) 3-O-Methylfunicone induces apoptosis and hsp70 activation in HeLa cells. Cell Prolif 37:413–426CrossRefGoogle Scholar
  2. Ciavatta ML, Lopez-Gresa MP, Carella A, Manzo E, Nicoletti R (2006) Antagonism toward Rhizoctonia solani and production of a brevioxime-related compound by Penicillium sizovae. J Plant Pathol 88:S37Google Scholar
  3. Cramer LP, Siebert M, Mitchison TJ (1997) Identification of novel graded polarity actin filament bundles in locomoting heart fibroblasts: implications for the generation of motile force. J Cell Biol 136:1287–1305CrossRefGoogle Scholar
  4. De Stefano S, Nicoletti R, Milone A, Zambardino S (1999) 3-O-Methylfunicone, a fungitoxic metabolite produced by the fungus Penicillium pinophilum. Phytochemistry 52:1399–1401CrossRefGoogle Scholar
  5. Fang N, Li Q, Yu S, Zhang J, He L, Ronis MJJ, Badger TM (2006) Inhibition of growth and induction of apoptosis in human cancer cell lines by an ethyl acetate fraction from shiitake mushrooms. J Altern Compl Med 12:125–132CrossRefGoogle Scholar
  6. Gonzalez del Val A, Platas G, Arenal F, Orihuela JC, Garcia M, Hernandez P, Royo I, De Pedro N, Silver LL, Young K, Vicente MF, Pelaez F (2003) Novel illudins from Coprinopsis episcopalis (syn. Coprinus episcopalis), and the distribution of illudin-like compounds among filamentous fungi. Mycol Res 107:1201–1209CrossRefGoogle Scholar
  7. Ho YS, Duh JS, Jeng JH, Wang YJ, Liang YC, Lin CH, Tseng CJ, Yu CF, Chen RJ, Lin JK (2001) Griseofulvin potentiates antitumorigenesis effects of nocodazole through induction of apoptosis and G2/M cell cycle arrest in human colorectal cancer cells. Int J Cancer 91:393–401CrossRefGoogle Scholar
  8. Kozakiewicz Z (1992) IMI descriptions of fungi and bacteria. No. 1105. Penicillium glabrum. Mycopathologia 117:173–174CrossRefGoogle Scholar
  9. Larsen TO, Smedsgaard J, Nielsen KF, Hansen ME, Frisvad JC (2005) Phenotypic taxonomy and metabolite profiling in drug discovery. Nat Prod Rep 22:672–695CrossRefGoogle Scholar
  10. Lipsky JL (1996) Mycophenolate mofetil. Lancet 348:1357–1359CrossRefGoogle Scholar
  11. Mahmoodian A, Stickings CE (1964) Studies in the biochemistry of micro-organisms. 115. Metabolites of Penicillium frequentans Westling: isolation of sulochrin, asterric acid, (+)-bisdechlorogeodin and two new substituted anthraquinones, questin and questinol. Biochem J 92:369–378Google Scholar
  12. Nicoletti R, Raimo F, Cozzolino E (2002) In vitro evaluation of fungal antagonists of Phytophthora nicotianae. Plant Prot Sci 38:52–55Google Scholar
  13. Nicoletti R, Raimo F, Carella A (2003) Searching Penicillium isolates antagonistic to Rhizoctonia solani in suppressive soils in Salento. J Plant Pathol 85:295Google Scholar
  14. Nicoletti R, De Stefano M, De Stefano S, Trincone A, Marziano F (2004) Identification of fungitoxic metabolites produced by some Penicillium isolates antagonistic to Rhizoctonia solani. Mycopathologia 158:465–474CrossRefGoogle Scholar
  15. Nicoletti R, Lopez-Gresa MP, Manzo E, Carella A, Ciavatta ML (2007) Production and fungitoxic activity of Sch 642305, a secondary metabolite of Penicillium canescens. Mycopathologia 163:295–301CrossRefGoogle Scholar
  16. Panda D, Rathinasamy K, Santra MK, Wilson L (2005) Kinetic suppression of microtubule dynamic instability by griseofulvin: implications for its possible use in the treatment of cancer. Proc Natl Acad Sci 102:9878–9883CrossRefGoogle Scholar
  17. Pawlak G, Helfman DM (2001) Cytoskeletal changes in cell transformation and tumorigenesis. Curr Opin Genet Develop 11:41–47CrossRefGoogle Scholar
  18. Radu S, Kqueen CY (2002) Preliminary screening of endophytic fungi from medicinal plants in Malaysia for antimicrobial and antitumor activity. Malaysian J Med Sci 9(2):23–33Google Scholar
  19. Saadat F, Zomorodian K, Pezeshki M, Rezaie S, Khorramizadeh MR (2004) Inhibitory effect of Aspergillus fumigatus extract on matrix metalloproteinases expression. Mycopathologia 158:33–37CrossRefGoogle Scholar
  20. Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning: a laboratory manual 2nd edn. Cold Spring Harbor Laboratory Press, Cold Spring HarborGoogle Scholar
  21. Sen S (1992) Programmed cell death: concept, mechanism and control. Biol Rev Cambridge Philos Soc 67:287–319Google Scholar
  22. Shimizu M, Nakamura M, Kataoka T, Iwaguchi T (1983) Mechanism of the antitumor activity of 5,5′-bis(2′-tetrahydropyranyl) secalonic acid D against Meth-A. Cancer Chemother Pharmacol 11:144–146CrossRefGoogle Scholar
  23. Stammati A, Nicoletti R, De Stefano S, Zampaglioni F, Zucco F (2002) A novel cytostatic compound derived from the fungus Penicillium pinophilum. Altern Labor Anim 30:69–75Google Scholar
  24. Stierle A, Stierle D, Strobel G, Bignami G, Grothaus P (1995) Bioactive metabolites of the endophytic fungi of Pacific yew, Taxus brevifolia: paclitaxel, taxanes, and other bioactive compounds. In: Georg GI, Chen TT, Ojima I, Vyas DM (eds) Taxane anticancer agents: basic science and current status. ACS Symposium Series 583, Washington, pp. 81–97Google Scholar
  25. Strobel G, Daisy B (2003) Bioprospecting for microbial endophytes and their natural products. Microbiol Mol Biol Rev 67:491–502CrossRefGoogle Scholar
  26. Tufano MA, Buommino E, Nicoletti R, Baroni A, Manzo E, Ciavatta ML (2005) Attività antifungina e antitumorale di filtrati colturali di un nuovo isolato di Penicillium canescens. Italian Patent NA2005A000042, 2 Aug 2005Google Scholar
  27. Unyayar A, Demirbilek M, Turkoglu M, Mazmanci MA, Erkurt EA, Unyayar S, Cekic O, Celik A, Atacag H (2005) Cytotoxic activities of Funalia trogii (Berk.) Bond. et Singer ATCC 200800 bioactive extract on HeLa cells and fibroblast cells. Int J Med Mushrooms 7:478–479Google Scholar
  28. Wani MC, Taylor HL, Wall ME, Goggon P, McPhail P (1971) Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. J Am Chem Soc 93:2325–2327CrossRefGoogle Scholar
  29. Waskewich C, Blumenthal RD, Li H, Stein R, Goldenberg DM, Burton J (2002) Celecoxib exhibits the greatest potency amongst cyclooxygenase (COX) inhibitors for growth inhibition of COX-2-negative hematopoietic and epithelial cell lines. Cancer Res 62:2029–2033Google Scholar
  30. Wendy Hsiao WL, Li YQ, Lee TL, Li N, You MM, Chang S (2004) Medicinal mushroom extracts inhibit ras-induced cell transformation and the inhibitory effect requires the presence of normal cells. Carcinogenesis 25:1177–1183CrossRefGoogle Scholar
  31. Whipps JM (2001) Microbial interactions and biocontrol in the rhizosphere. J Exp Bot 52:487–511Google Scholar

Copyright information

© Springer Science+Business Media B.V. 2007

Authors and Affiliations

  • Rosario Nicoletti
    • 1
  • Elisabetta Buommino
    • 2
  • Anna De Filippis
    • 2
  • Maria Pilar Lopez-Gresa
    • 3
  • Emiliano Manzo
    • 3
  • Angela Carella
    • 1
  • Marcella Petrazzuolo
    • 2
  • Maria Antonietta Tufano
    • 2
  1. 1.C.R.A. – Tobacco Experiment InstituteScafatiItaly
  2. 2.Department of Experimental Medicine, Section of Microbiology and Clinical MicrobiologyThe Second University of NaplesNapoliItaly
  3. 3.Institute of Biomolecular ChemistryC.N.RPozzuoliItaly

Personalised recommendations