期刊
FOOD AND CHEMICAL TOXICOLOGY
卷 124, 期 -, 页码 30-44出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2018.11.043
关键词
Ganoderma tsugae; Human chronic myeloid leukemia; G2/M arrest; Apoptosis; Autophagy
资金
- Ministry of Science and Technology, Taiwan [MOST-106-2320-B-039-054-MY3, MOST-104-2320-B-039-040-MY3]
- Chinese Medicine Research Center, China Medical University from the Featured Areas Research Center Program within the Higher Education Sprout Project by the Ministry of Education in Taiwan [CMRC-CHM-9]
The medicinal fungus Ganoderma, known in Chinese as Lingzhi or Reishi, traditionally has various medicinal uses and has been employed in cancer treatment in Asia for centuries. This study used ethanol-extracted Ganoderma tsugae (GT) and examined its antitumor activities on human chronic myeloid leukemia cells as well as its molecular mechanism of action. Treatment with GT (200-400 mu g/mL) significantly reduced cell viability and caused G2/M arrest in K562 cells. In addition, GT induced mitochondrial and death receptor mediated apoptosis, correlated with DNA fragmentation, followed by cytochrome c release, caspase-3/8/9 activation, PARP cleavage, Fas activation, Bid cleavage, and Bax/Bcl-2 dysregulation. Cytoprotective autophagy was found to be induced by GT, as was revealed by increased LC3-II accumulation, Beclin-1/Bcl-2 dysregulation, acidic vesicular organelle formation, and p62/SQSTM1 activation. Notably, pretreatment of cells with the autophagy inhibitors 3-MA and CQ enhanced GT-induced apoptosis. Interestingly, reactive oxygen species production in cells was not triggered by GT administration; equally, the antioxidant N-acetylcysteine was found to be incapable of preventing apoptosis and autophagy induced by GT treatment. Finally, this study discovered that cytoprotective autophagy induced by GT was associated with EGFR and PI3K/AKT/mTOR signaling cascade suppression. In summary, GT demonstrated antitumor activity against human chronic myeloid leukemia.
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