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J Ethnopharmacol. 2014 Apr 28;153(2):499-510. doi: 10.1016/j.jep.2014.03.012. Epub 2014 Mar 14.

The anti-tumor activity of Antrodia salmonea in human promyelocytic leukemia (HL-60) cells is mediated via the induction of G₁ cell-cycle arrest and apoptosis in vitro or in vivo.

Author information

1
Department of Cosmeceutics, College of Pharmacy, China Medical University, Taichung 40402, Taiwan; Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan.
2
Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan.
3
Department of Applied Chemistry, Chao Yang University of Technology, Taichung 41349, Taiwan.
4
Department of Cosmeceutics, College of Pharmacy, China Medical University, Taichung 40402, Taiwan.
5
Institute of Nutrition, China Medical University, Taichung 40402, Taiwan.
6
Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 40402, Taiwan.
7
School of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Pharmacy, China Medical University, Taichung 40402, Taiwan.
8
Institute of Nutrition, China Medical University, Taichung 40402, Taiwan. Electronic address: hlyang@mail.cmu.edu.tw.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE:

The medicinal mushroom Antrodia salmonea has been used as a traditional Chinese medicine and has demonstrated antioxidant and anti-inflammatory effects.

MATERIALS AND METHODS:

In the present study, we examined the anti-tumor activity of the fermented culture broth of Antrodia salmonea (AS) in vitro and in vivo and revealed its underlying molecular mechanism of action.

RESULTS:

Treatment of human promyelocytic leukemia (HL-60) cells with AS (50-150 μg/mL) significantly reduced cell viability and caused G1 arrest via the inhibition of cell-cycle regulatory proteins, including cyclin D1, CDK4, cyclin E, cyclin A, and phosphorylated retinoblastoma protein (p-Rb). Furthermore, AS treatment induced apoptosis, which was associated with DNA fragmentation, followed by a sequence of events, including intracellular ROS generation; mitochondrial dysfunction; Fas ligand activation; cytochrome c release; caspase-3, -8, -9, and PARP activation; and Bcl-2/Bax dysregulation. The results of the in vitro study suggested that AS-induced apoptosis in HL-60 cells was mediated by both the mitochondrial and death receptor pathways. Furthermore, we found that AS treatment was effective in delaying tumor incidence in HL-60 xenografted nude mice and reducing tumor burden.

CONCLUSIONS:

To the best of our knowledge, this is the first report confirming the anti-tumor activity of this potentially beneficial mushroom against human promyelocytic leukemia.

KEYWORDS:

Antrodia salmonea; Apoptosis; G(1) cell-cycle arrest; Human promyelocytic leukemia; Xenografted nude mice

PMID:
24631961
DOI:
10.1016/j.jep.2014.03.012
[Indexed for MEDLINE]

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