Skip to main content

Aqueous and Ethanolic Extracts of Medicinal Mushroom Trametes versicolor Interact with DNA: A Novel Genoactive Effect Contributing to Its Antiproliferative Activity in Cancer Cells

  • Chapter
  • First Online:

Abstract

Trametes versicolor, a medicinal mushroom also known as Yunzhi, has been widely consumed in China as a dietary supplement by individuals diagnosed with various chronic diseases including cancer. Laboratory studies have shown that aqueous and ethanolic extracts of Trametes versicolor enhance immune functions and also inhibit the growth of various cancer cells both in vitro and in vivo. However, knowledge of the mechanism by which Trametes versicolor exerts its chemotherapeutic action remains incomplete. Efforts to identify its bioactive ingredients have resulted in the isolation of a heterogeneous family of polysaccharopeptides (PSPs). In this study, we investigated whether aqueous and ethanolic extracts of Trametes versicolor elicit its antitumor effects by interacting with and changing structure and function of DNA and this novel genoactivity might contribute to suppression of proliferation of human lung A549 cancer cells. Using pBR322 and pSJ3 supercoiled plasmid DNA as substrates, we showed that incubation of DNA with both aqueous and ethanolic extracts of Trametes versicolor causes relaxation of double-stranded supercoiled DNA in a concentration- and time-dependent manner. Comparatively, aqueous extracts showed higher conversion rates of supercoiled to relaxed DNA than ethanolic extracts. Aqueous extracts also significantly inhibited A549 lung cancer cell proliferation, downregulated proliferating cell nuclear antigen (PCNA) expression, as well as disrupted cell cycle progression via suppression of levels of cyclins D1 and B. This suggests that immunomodulatory and adjunctive supplementary chemopreventive potential underlying the overall health beneficial effects of Trametes versicolor may involve a novel genoactive activity with potential in altering DNA structure and function.

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

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
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

Learn about institutional subscriptions

Abbreviations

ATCC:

American Type Culture Conditions

CPT:

Camptothecin

ECL:

Enhanced chemiluminescence

FBS:

Fetal bovine serum

GMP:

Good Manufacturing Practice

MTT:

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide

PBS:

Phosphate-buffered saline

PSPs:

Polysaccharopeptides isolated from the medicinal mushroom Trametes versicolor

UV-visible:

Ultraviolet-visible

YZ:

Yunzhi

References

  • Borchers AT, Keen CL, Gershwin ME (2004) Mushrooms, tumors, and immunity: an update. Exp Biol Med (Maywood) 229(5):393–406

    Article  CAS  Google Scholar 

  • Borchers AT, Stern JS, Hackman RM, Keen CL, Gershwin ME (1999) Mushrooms, tumors, and immunity. Proc Soc Exp Biol Med 221(4):281–293

    CAS  PubMed  Google Scholar 

  • Chang ST, Wasser SP (2012) The role of culinary-medicinal mushrooms on human welfare with a pyramid model for human health. Int J Med Mushrooms 14(2):95–134

    Article  Google Scholar 

  • Chu KK, Ho SS, Chow AH (2002) Coriolus versicolor: a medicinal mushroom with promising immunotherapeutic values. J Clin Pharmacol 42(9):976–984

    Article  Google Scholar 

  • Cui J, Chisti Y (2003) Polysaccharopeptides of Coriolus versicolor: physiological activity, uses, and production. Biotechnol Adv 21(2):109–122

    Article  CAS  Google Scholar 

  • Fukuhara K, Miyata N (1998) Resveratrol as a new type of DNA-cleaving agent. Bioorg Med Chem Lett 8(22):3187–3192

    Article  CAS  Google Scholar 

  • Fukuhara K, Nagakawa M, Nakanishi I, Ohkubo K, Imai K, Urano S et al (2006) Structural basis for DNA-cleaving activity of resveratrol in the presence of Cu(II). Bioorg Med Chem 14(5):1437–1443. https://doi.org/10.1016/j.bmc.2005.09.070

    Article  CAS  PubMed  Google Scholar 

  • Hofland H, Huang L (1995) Inhibition of human ovarian carcinoma cell proliferation by liposome-plasmid DNA complex. Biochem Biophys Res Commun 207(2):492–496. https://doi.org/10.1006/bbrc.1995.1215

    Article  CAS  PubMed  Google Scholar 

  • Hsieh TC, Elangovan S, Wu JM (2010) Differential suppression of proliferation in MCF-7 and MDA-MB-231 breast cancer cells exposed to alpha-, gamma- and delta-tocotrienols is accompanied by altered expression of oxidative stress modulatory enzymes. Anticancer Res 30(10):4169–4176

    CAS  PubMed  Google Scholar 

  • Hsieh TC, Kunicki J, Darzynkiewicz Z, Wu JM (2002) Effects of extracts of Coriolus versicolor (I’m-Yunity) on cell-cycle progression and expression of interleukins-1 beta,-6, and -8 in promyelocytic HL-60 leukemic cells and mitogenically stimulated and nonstimulated human lymphocytes. J Altern Complement Med 8(5):591–602

    Article  Google Scholar 

  • Hsieh TC, Wu JM (2001) Cell growth and gene modulatory activities of Yunzhi (Windsor Wunxi) from mushroom Trametes versicolor in androgen-dependent and androgen-insensitive human prostate cancer cells. Int J Oncol 18(1):81–88

    CAS  PubMed  Google Scholar 

  • Hsieh TC, Wu JM (2006) Differential control of growth, cell cycle progression, and gene expression in human estrogen receptor positive MCF-7 breast cancer cells by extracts derived from polysaccharopeptide I’m-Yunity and Danshen and their combination. Int J Oncol 29(5):1215–1222

    CAS  PubMed  Google Scholar 

  • Hsieh TC, Wu JM (2013) Regulation of cell cycle transition and induction of apoptosis in HL-60 leukemia cells by the combination of Coriolus versicolor and Ganoderma lucidum. Int J Mol Med 32(1):251–257. https://doi.org/10.3892/ijmm.2013.1378

    Article  PubMed  Google Scholar 

  • Hsieh TC, Wu P, Park S, Wu JM (2006) Induction of cell cycle changes and modulation of apoptogenic/anti-apoptotic and extracellular signaling regulatory protein expression by water extracts of I’m-Yunity (PSP). BMC Complement Altern Med 6:30

    Article  Google Scholar 

  • Hui KP, Sit WH, Wan JM (2005) Induction of S phase cell arrest and caspase activation by polysaccharide peptide isolated from Coriolus versicolor enhanced the cell cycle dependent activity and apoptotic cell death of doxorubicin and etoposide, but not cytarabine in HL-60 cells. Oncol Rep 14(1):145–155

    CAS  PubMed  Google Scholar 

  • Kidd PM (2000) The use of mushroom glucans and proteoglycans in cancer treatment. Altern Med Rev 5(1):4–27

    CAS  PubMed  Google Scholar 

  • Lee YS, Doonan BB, Wu JM, Hsieh TC (2016) Combined metformin and resveratrol confers protection against UVC-induced DNA damage in A549 lung cancer cells via modulation of cell cycle checkpoints and DNA repair. Oncol Rep 35(6):3735–3741. https://doi.org/10.3892/or.2016.4740

    Article  CAS  PubMed  Google Scholar 

  • Li Z, Yang X, Dong S, Li X (2012) DNA breakage induced by piceatannol and copper(II): mechanism and anticancer properties. Oncol Lett 3(5):1087–1094. https://doi.org/10.3892/ol.2012.597

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maniatis T, Fritsch EF, Sambrook J (1982) Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor

    Google Scholar 

  • Ooi VE, Liu F (2000) Immunomodulation and anti-cancer activity of polysaccharide-protein complexes. Curr Med Chem 7(7):715–729

    Article  CAS  Google Scholar 

  • Patel S, Goyal A (2012) Recent developments in mushrooms as anti-cancer therapeutics: a review. 3 Biotech 2(1):1–15. https://doi.org/10.1007/s13205-011-0036-2

    Article  PubMed  Google Scholar 

  • Traganos F, Kapuscinski J, Darzynkiewicz Z (1991) Caffeine modulates the effects of DNA-intercalating drugs in vitro: a flow cytometric and spectrophotometric analysis of caffeine interaction with novantrone, doxorubicin, ellipticine, and the doxorubicin analogue AD198. Cancer Res 51(14):3682–3689

    CAS  PubMed  Google Scholar 

  • Wan JM, Sit WH, Louie JC (2008) Polysaccharopeptide enhances the anticancer activity of doxorubicin and etoposide on human breast cancer cells ZR-75-30. Int J Oncol 32(3):689–699

    CAS  PubMed  Google Scholar 

  • Wan JM, Sit WH, Yang X, Jiang P, Wong LL (2010) Polysaccharopeptides derived from Coriolus versicolor potentiate the S-phase specific cytotoxicity of Camptothecin (CPT) on human leukemia HL-60 cells. Chin Med 5:16

    Article  Google Scholar 

  • Wasser SP, Weis AL (1999) Therapeutic effects of substances occurring in higher Basidiomycetes mushrooms: a modern perspective. Crit Rev Immunol 19(1):65–96

    CAS  PubMed  Google Scholar 

  • Wenner CA, Martzen MR, Lu H, Verneris MR, Wang H, Slaton JW (2012) Polysaccharide-K augments docetaxel-induced tumor suppression and antitumor immune response in an immunocompetent murine model of human prostate cancer. Int J Oncol 40(4):905–913. https://doi.org/10.3892/ijo.2011.1292

    Article  CAS  PubMed  Google Scholar 

  • Yang X, Sit WH, Chan DK, Wan JM (2005) The cell death process of the anticancer agent polysaccharide-peptide (PSP) in human promyelocytic leukemic HL-60 cells. Oncol Rep 13(6):1201–1210

    CAS  PubMed  Google Scholar 

  • Yokoyama A, Natori S, Aoshima K (1975) Distribution of tetracyclic triterpenoids of lanostane group and sterols in the higher fungi especially of the Polyporaceae and related families. Phytochemistry 14(2):487–497. https://doi.org/10.1016/0031-9422(75)85115-6

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Joseph M. Wu .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Hsieh, TC., Chao, H.H., Chu, Y., Doonan, B.B., Wu, J.M. (2019). Aqueous and Ethanolic Extracts of Medicinal Mushroom Trametes versicolor Interact with DNA: A Novel Genoactive Effect Contributing to Its Antiproliferative Activity in Cancer Cells. In: Agrawal, D., Dhanasekaran, M. (eds) Medicinal Mushrooms. Springer, Singapore. https://doi.org/10.1007/978-981-13-6382-5_7

Download citation

Publish with us

Policies and ethics