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Int. J. Mol. Sci. 2018, 19(2), 393; https://doi.org/10.3390/ijms19020393

Anti-Cancerous Effect of Inonotus taiwanensis Polysaccharide Extract on Human Acute Monocytic Leukemia Cells through ROS-Independent Intrinsic Mitochondrial Pathway

1
Departments of Laboratory Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
2
Department of Medical Laboratory Science and Biotechnology, Fooyin University, Kaohsiung 831, Taiwan
3
Department of Laboratory Medicine, Yunlin Christian Hospital, Yunlin 648, Taiwan
4
Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan
5
Department of Nursing, Tajen University, Pintung 907, Taiwan
6
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
7
Department of Biology, National Museum of Natural Science, Taichung 404, Taiwan
*
Author to whom correspondence should be addressed.
Received: 13 November 2017 / Revised: 3 January 2018 / Accepted: 19 January 2018 / Published: 29 January 2018
(This article belongs to the Section Bioactives and Nutraceuticals)
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Abstract

Acute leukemia is one of the commonly diagnosed neoplasms and causes human death. However, the treatment for acute leukemia is not yet satisfactory. Studies have shown that mushroom-derived polysaccharides display low toxicity and have been used clinically for cancer therapy. Therefore, we set out to evaluate the anti-cancerous efficacy of a water-soluble polysaccharide extract from Inonotus taiwanensis (WSPIS) on human acute monocytic leukemia THP-1 and U937 cell lines in vitro. Under our experimental conditions, WSPIS elicited dose-dependent growth retardation and induced apoptotic cell death. Further analysis showed that WSPIS-induced apoptosis was associated with a mitochondrial apoptotic pathway, such as the disruption of mitochondrial membrane potential (MMP), followed by the activation of caspase-9, caspase-3, and PARP (poly(ADP-ribose) polymerase) cleavage. However, a broad caspase inhibitor, Z-VAD.fmk, could not prevent WSPIS-induced apoptosis. These data imply that mechanism(s) other than caspase might be involved. Thus, the involvement of endonuclease G (endoG), a mediator arbitrating caspase-independent oligonucleosomal DNA fragmentation, was examined. Western blotting demonstrated that WSPIS could elicit nuclear translocation of endoG. MMP disruption after WSPIS treatment was accompanied by intracellular reactive oxygen species (ROS) generation. However, pretreatment with N-acetyl-l-cysteine (NAC) could not attenuate WSPIS-induced apoptosis. In addition, our data also show that WSPIS could inhibit autophagy. Activation of autophagy by rapamycin decreased WSPIS-induced apoptosis and cell death. Taken together, our findings suggest that cell cycle arrest, endonuclease G-mediated apoptosis, and autophagy inhibition contribute to the anti-cancerous effect of WSPIS on human acute monocytic leukemia cells. View Full-Text
Keywords: Inonotus taiwanensis; human acute monocytic leukemia cell line; apoptosis; endonuclease G Inonotus taiwanensis; human acute monocytic leukemia cell line; apoptosis; endonuclease G
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Chao, T.-L.; Wang, T.-Y.; Lee, C.-H.; Yiin, S.-J.; Ho, C.-T.; Wu, S.-H.; You, H.-L.; Chern, C.-L. Anti-Cancerous Effect of Inonotus taiwanensis Polysaccharide Extract on Human Acute Monocytic Leukemia Cells through ROS-Independent Intrinsic Mitochondrial Pathway. Int. J. Mol. Sci. 2018, 19, 393.

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