Tumor Biology

, Volume 37, Issue 10, pp 14291–14300 | Cite as

Armillaridin induces autophagy-associated cell death in human chronic myelogenous leukemia K562 cells

  • Wen-Han Chang
  • Huey-Lan Huang
  • Wei-Pang Huang
  • Chien-Chih Chen
  • Yu-Jen Chen
Original Article


Armillaridin (AM) is an aromatic ester compound isolated from Armillaria mellea. Treatment with AM markedly reduced the viability of human chronic myelogenous leukemia K562, chronic erythroleukemia HEL 92.1.7, and acute monoblastic leukemia U937 cells, but not normal human monocytes, in a dose- and time-dependent manner. Treatment of K562 cells with AM caused changes characteristic of autophagy. Only a small amount of AM-treated K562 cells exhibited apoptosis. By contrast, AM treatment resulted in extensive apoptotic features in U937 and HEL 92.1.7 cells without evident autophagy. The autophagy of K562 cells induced by AM involved autophagic flux, including autophagosome induction, the processing of autophagosome-lysosome fusion and downregulation of BCL2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3). By bcr-abl knockdown, the growth inhibition of K562 cells caused by AM was partially blocked, suggesting that AM-induced cell death might be a bcr-abl-dependent mode of autophagy-associated cell death. In conclusion, AM is capable of inhibiting growth and inducing autophagy-associated cell death in K562 cells, but not in normal monocytes. It may have potential to be developed as a novel therapeutic agent against leukemia.


Armillaridin Autophagy bcr-abl BNIP3 Chronic myelogenous leukemia 





BCL2/adenovirus E1B 19 kDa interacting protein 3


Chronic myelogenous leukemia






Signal transduction inhibitor-571



We want to thank Dr. King-Song Jeng and the National RNAi Core Facility, Academia Sinica, Taiwan, for shRNA knockdown techniques, the pTRC-905 vector, and the pTRC-905-shBCR constructions. This work was supported by grant NSC98-2323-B-241 from the National Science Council, Taiwan, and grant 09MMHIS027 and MMH-E-105-13, E-104-13 from MacKay Memorial Hospital, Taiwan.

Compliance with ethical standards

Conflicts of interest


Supplementary material

13277_2016_5208_Fig10_ESM.gif (176 kb)
Supplemental Figure 1.

Effect of armillaridin on BCR-ABL expression on K562 cells. Cells were untreated, treated with 0.1% DMSO (solvent), 10 μM armillaridin for 24 hours or starvation for 6 hours. Protein extracts from whole cells were subjected to Western blotting. Data from three separate experiments showed similar trend. No significant differences on the expression of BCR-ABL were found between control and armillaridin treatment. (GIF 175 kb)

13277_2016_5208_MOESM1_ESM.tiff (1.5 mb)
High Resolution Image (TIFF 1521 kb)


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  1. 1.Institute of Traditional MedicineNational Yang-Ming UniversityTaipeiTaiwan
  2. 2.Department of Healthcare CenterMacKay Memorial HospitalNew Taipei CityTaiwan
  3. 3.Department of Bioscience Technology, College of Health ScienceChang Jung Christian UniversityTainanTaiwan
  4. 4.Department of Life Science and Institute of ZoologyNational Taiwan UniversityTaipeiTaiwan
  5. 5.Department of BiotechnologyHungkuang UniversityTaichung CityTaiwan
  6. 6.Department of Medical ResearchMacKay Memorial HospitalTaipei CityTaiwan
  7. 7.Department of Radiation OncologyMacKay Memorial HospitalTaipei CityTaiwan

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