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

Autor: Chin Huei Lee, Tsai Ling Chao, Chi-Liang Chern, Chun Te Ho, Ting Yin Wang, Shuenn Jiun Yiin, Huey Ling You, Sheng-Hua Wu
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Monocytes
lcsh:Chemistry
0302 clinical medicine
Acute monocytic leukemia
endonuclease G
lcsh:QH301-705.5
Spectroscopy
Membrane Potential
Mitochondrial
Acute leukemia
Chemistry
apoptosis
General Medicine
Inonotus taiwanensis
Caspase Inhibitors
Computer Science Applications
Mitochondria
Leukemia
Myeloid
030220 oncology & carcinogenesis
DNA fragmentation
Programmed cell death
human acute monocytic leukemia cell line
Poly ADP ribose polymerase
ENDOG
Antineoplastic Agents
DNA Fragmentation
Catalysis
Article
Inorganic Chemistry
03 medical and health sciences
Cell Line
Tumor
medicine
Autophagy
Humans
Physical and Theoretical Chemistry
Molecular Biology
Endodeoxyribonucleases
Basidiomycota
Organic Chemistry
Fungal Polysaccharides
medicine.disease
Acetylcysteine
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
Apoptosis
Cancer research
Reactive Oxygen Species
Zdroj: International Journal of Molecular Sciences; Volume 19; Issue 2; Pages: 393
International Journal of Molecular Sciences
International Journal of Molecular Sciences, Vol 19, Iss 2, p 393 (2018)
ISSN: 1422-0067
DOI: 10.3390/ijms19020393
Popis: 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.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje