Skip to main content
SpringerLink
Log in

Khz (fusion of ganoderma lucidum and Polyporus umbellatus mycelia) induces apoptosis in A549 human lung cancer cells by generating reactive oxygen species and decreasing the mitochondrial membrane potential

  • Research Article
  • Published:
Food Science and Biotechnology Aims and scope Submit manuscript

Abstract

Khz, a naturally occurring compound derived from the fusion of Ganoderma lucidum and Polyporus umbellatus mycelia, inhibits the growth of cancer cells. This study aimed to investigate the anti-proliferative effects of Khz on A549 lung cancer cells. Khz cytotoxicity was measured using an MTT assay and the mitochondrial membrane potential (MMP)-related, calcium-induced generation of reactive oxygen species (ROS) in A549 cells was measured by flow cytometry. The expression of p53, Bax, Bcl-2, and actin proteins was analyzed by western blotting. Khz inhibited cell division and induced apoptosis in A549 cells. Flow cytometry analysis showed that the percentage of A549 cells in sub-G1 phase of the cell cycle increased in response to Khz treatment. Khz reduced MMP and Bcl-2 protein levels, but increased ROS generation and p53 and pro-apoptotic proteins. The anti-proliferative and pro-apoptotic effects of Khz suggest that this extract shows great promise as a potential chemotherapeutic agent.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Refrerences

  1. Lin ZB, Zhang HN. Anti-tumor and immunoregulatory activities of Ganoderma lucidum and its possible mechanisms. Acta Pharmacol. Sin. 25: 1387–1395 (2004)

    CAS  Google Scholar 

  2. Sandodiya BS, Thakur GS, Baqhel RK, Prasad GB, Bisen PS. Ganoderma lucidum: A potent pharmacological macrofungus. Curr. Pharm. Biotechnol. 10: 717–742 (2009)

    Article  Google Scholar 

  3. Gao Y, Gao H, Chan E, Tang W, Xu A, Yang H, Huang M, Lan J, Li X, Duan W, Xu C, Zhou S. Antitumor activity and underlying mechanisms of ganopoly,the refined polysaccarides extracted from Ganoderma lucidum, in mice. Immunol. Invest. 34: 171–198 (2005)

    Article  CAS  Google Scholar 

  4. Yue GG, Fung KP, Tse GM, Leung PC, Lau CB. Comparative studies of various ganoderma species and their different parts with regard to antitumor and immunomodulating activities in vitro. J. Altern. Complement. Med. 12: 777–789 (2006)

    Article  Google Scholar 

  5. IIIana-Esteban C. The fungus maitake (Grifola frondosa) and its therapeutic potential. Rev. Iberoam. Micol. 25: 141–144 (2008)

    Article  Google Scholar 

  6. Jang KJ, Han MH, Lee BH, Kim BW, Kim CH, Yoon HM, Choi YH. Induction of apoptosis by ethanol extracts of Ganoderma lucidum in human gastric carcinoma cells. J. Acupunct. Meridian Stud. 3: 24–31 (2010)

    Article  Google Scholar 

  7. Yue QX, Song XY, Ma C, Feng LX, Guan SH, Wu WY, Yang M, Jiang BH, Liu X, Cui YJ, Guo DA. Effects of triterpenes from Ganoderma lucidum on protein expression profile of HeLa cells. Phytomedicine 17: 606–613 (2010)

    Article  CAS  Google Scholar 

  8. Zhao S, Ye G, Fu G, Cheng JX, Yang BB, Peng C. Ganoderma lucidum exerts anti-tumor effects on ovarian cancer cells and enhances their sensitivity to cisplatin. Int. J. Oncol. 38: 1319–1327 (2011)

    Google Scholar 

  9. Liu RM, Zhong JJ. Ganoderic acid Mf and S induce mitochondria mediated apoptosis in human cervical carcinoma HeLa cells. Phytomedicine 15: 349–355 (2011)

    Article  Google Scholar 

  10. Li L, Li T, Wang XJ, Xu JP, Wang SG. Effects of Ganoderma lucidum spores on HepG2 cells proliferation and growth cycle. Zhong Yao Cai 31: 1514–1518 (2008)

    CAS  Google Scholar 

  11. Zhao YY, Chao X, Zhang Y, Lin RC, Sun WJ. Cytotoxic steroids from Polyporus umbellatus. Planta Med. 76: 1755–1758 (2010)

    Article  CAS  Google Scholar 

  12. Ott M, Gogvadze V, Orrenius S, Zhivotovsky B. Mitochondria, oxidative stress and cell death. Apoptosis 12: 913–922 (2007)

    Article  CAS  Google Scholar 

  13. Jacobson MD, Raff MC. Programmed cell death and Bcl-2 protection in very low oxygen. Nature 374: 814–816 (1995)

    Article  CAS  Google Scholar 

  14. Kim TH, Kim Js, Kim Zh, Huang RB, Wang RS. Khz (fusion of Ganoderma lucidum and Polyporus umbellatus mycelia) induces apoptosis by increasing intracellular calcium levels and activating JNK and NADPH oxidase-dependent generation of reactive oxygen species. PLoS One. 7: e46208 (2012)

  15. Ryter SW, Kim HP, Hoetzel A, Park JW, Nakahira K, Wang X, Choi AM. Mechanisms of cell death in oxidative stress. Antioxid. Redox Sign. 9: 49–89 (2007)

    Article  CAS  Google Scholar 

  16. Buttke TM, Sandstrom PA. Oxidative stress as a mediator of apoptosis. Immunol. Today. 15: 7–10 (1994)

    Article  CAS  Google Scholar 

  17. Jacobson MD. Reactive oxygen species and programmed cell death. Trends Biochem. Sci. 21: 83–86 (1996)

    Article  CAS  Google Scholar 

  18. Miyajima, A, Nakashima J, Yoshioka K. Role of reactive oxygen species in cis-dichlorodiammineplatium-induced cytotoxicity on bladder cancer cells. Brit. J. Cancer 76: 206–210 (1997)

    Article  CAS  Google Scholar 

  19. Zhou Y, Hileman EO, Plunkett W, Keating MJ, Huang P. Free radical stress in chronic lymphocytic leukemia cells and its role in cellular sensitivity to ROS-generating anticancer agents. Blood 101: 4098–4104 (2003)

    Article  CAS  Google Scholar 

  20. Nicotera P, Orrenius S. The role of calcium in apoptosis. Cell Calcium 23: 173–180 (1998)

    Article  CAS  Google Scholar 

  21. Granfeldt D, Samuelsson M, Karlsson A. Capacitative Ca2+ influx and activation of the neutrophil respiratory burst. Different regulation of plasma membrane- and granule-localized NADPHoxidase. J. Leukocyte Biol. 71: 611–617 (2002)

    CAS  Google Scholar 

  22. Wang G, Anrather J, Glass MJ, Tarsitano MJ, Zhou P, Frys KA, Pickel VM, Iadecola C. Nox2, Ca2+, and protein kinase C play a role in angiotensin II-induced free radical production in nucleus tractus solitaries. Hypertension 48: 482–489 (2006)

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Radiotherapy, The First Affiliated Hospital, Guangxi Medical University, Nanning, 530021, China

    Tae Hwan Kim & Ren Sheng Wang

  2. Clinical Medicine, Harbin Medical University, Harbin, 150081, China

    Ju Sung Kim

  3. Graduate School of Information Science, Nagoya University, Nagoya, 466-8550, Japan

    Zoo Haye Kim

  4. Department of Pharmacology, Guangxi Medical University, Nanning, 530021, China

    Ren Bin Huang

Authors
  1. Tae Hwan Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ju Sung Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zoo Haye Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ren Bin Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ren Sheng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ren Sheng Wang.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, T.H., Kim, J.S., Kim, Z.H. et al. Khz (fusion of ganoderma lucidum and Polyporus umbellatus mycelia) induces apoptosis in A549 human lung cancer cells by generating reactive oxygen species and decreasing the mitochondrial membrane potential. Food Sci Biotechnol 23, 859–864 (2014). https://doi.org/10.1007/s10068-014-0115-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10068-014-0115-3

Keywords

Search

Navigation