Armillaridin induces autophagy-associated cell death in human chronic myelogenous leukemia K562 cells.
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.
Institute of Traditional Medicine, National Yang-Ming University, Taipei, 11221, Taiwan.|Department of Healthcare Center, MacKay Memorial Hospital, New Taipei City, 25173, Taiwan.
Wen-Han
WH
Chang
Department of Bioscience Technology, College of Health Science, Chang Jung Christian University, Tainan, 71101, Taiwan.
Huey-Lan
HL
Huang
Department of Life Science and Institute of Zoology, National Taiwan University, Taipei, 10617, Taiwan.
Wei-Pang
WP
Huang
Department of Biotechnology, Hungkuang University, No.1018, Sec. 6, Taiwan Boulevard, Shalu Dist., Taichung City, 43302, Taiwan. ccchen@sunrise.hk.edu.tw.
Chien-Chih
CC
Chen
Institute of Traditional Medicine, National Yang-Ming University, Taipei, 11221, Taiwan. chenmdphd@gmail.com.|Department of Medical Research, MacKay Memorial Hospital, No.92, Section 2, Zhongshan N. Rd., Zhongshan District, Taipei City, 10449, Taiwan. chenmdphd@gmail.com.|Department of Radiation Oncology, MacKay Memorial Hospital, No.92, Section 2, Zhongshan N. Rd., Zhongshan District, Taipei City, 10449, Taiwan. chenmdphd@gmail.com.
Yu-Jen
YJ
Chen
D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D008565:Membrane Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012717:Sesquiterpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
C090121:BNIP3 protein, human; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D012717:Sesquiterpenes; C043543:armillaridin; D020169:Caspases
Armillaridin; Autophagy; BNIP3; Chronic myelogenous leukemia; bcr-abl