Agarol, an ergosterol derivative from Agaricus blazei, induces caspase-independent apoptosis in human cancer cells

  • Authors:
    • Takamitsu Shimizu
    • Junya Kawai
    • Kenji Ouchi
    • Haruhisa Kikuchi
    • Yoshiteru Osima
    • Rikiishi Hidemi
  • View Affiliations

  • Published online on: February 15, 2016     https://doi.org/10.3892/ijo.2016.3391
  • Pages: 1670-1678
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Agaricus blazei (A. blazei) is a mushroom with many biological effects and active ingredients. We purified a tumoricidal substance from A. blazei, an ergosterol derivative, and named it ‘Agarol’. Cytotoxic effects of Agarol were determined by the MTT assay using A549, MKN45, HSC-3, and HSC-4 human carcinoma cell lines treated with Agarol. Apoptosis was detected by flow cytometry analysis. Reactive oxygen species (ROS) levels and mitochondria membrane potential (∆ψm) were also determined by flow cytometry. Western blot analysis was used to quantify the expression of apoptosis-related proteins. Agarol predominantly induced apoptosis in two p53-wild cell lines (A549 and MKN45) compared to the other p53-mutant cell lines (HSC-3 and HSC-4). Further mechanistic studies revealed that induction of apoptosis is associated with increased generation of ROS, reduced ∆ψm, release of apoptosis-inducing factor (AIF) from the mitochondria to the cytosol, upregulation of Bax, and downregulation of Bcl-2. Caspase-3 activities did not increase, and z-VAD-fmk, a caspase inhibitor, did not inhibit the Agarol-induced apoptosis. These findings indicate that Agarol induces caspase-independent apoptosis in human carcinoma cells through a mitochondrial pathway. The in vivo anticancer activity of Agarol was confirmed in a xenograft murine model. This study suggests a molecular mechanism by which Agarol induces apoptosis in human carcinoma cells and indicates the potential use of Agarol as an anticancer agent.
View Figures
View References

Related Articles

Journal Cover

April 2016
Volume 48 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Shimizu, T., Kawai, J., Ouchi, K., Kikuchi, H., Osima, Y., & Hidemi, R. (2016). Agarol, an ergosterol derivative from Agaricus blazei, induces caspase-independent apoptosis in human cancer cells. International Journal of Oncology, 48, 1670-1678. https://doi.org/10.3892/ijo.2016.3391
MLA
Shimizu, T., Kawai, J., Ouchi, K., Kikuchi, H., Osima, Y., Hidemi, R."Agarol, an ergosterol derivative from Agaricus blazei, induces caspase-independent apoptosis in human cancer cells". International Journal of Oncology 48.4 (2016): 1670-1678.
Chicago
Shimizu, T., Kawai, J., Ouchi, K., Kikuchi, H., Osima, Y., Hidemi, R."Agarol, an ergosterol derivative from Agaricus blazei, induces caspase-independent apoptosis in human cancer cells". International Journal of Oncology 48, no. 4 (2016): 1670-1678. https://doi.org/10.3892/ijo.2016.3391