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.

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.

• Authors: You-Cheng Hseu, Chuan-Chen Lee, Yung-Chang Chen, K J Senthil Kumar, Chee-Shan Chen, Yu-Chi Huang, Li-Sung Hsu, Hui-Chi Huang, Hsin-Ling Yang
• Journal: Journal of ethnopharmacology (J Ethnopharmacol) Vol. 153 Issue 2 Pg. 499-510 (Apr 28 2014) ISSN: 1872-7573 [Electronic] Ireland
• PMID: 24631961 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014. Published by Elsevier Ireland Ltd.

Chemical References

• Antineoplastic Agents

Topics

• Animals
• Antineoplastic Agents (isolation & purification, pharmacology, therapeutic use)
• Antrodia (isolation & purification)
• Apoptosis (drug effects, physiology)
• Cell Line
• Dose-Response Relationship, Drug
• Female
• G1 Phase Cell Cycle Checkpoints (drug effects, physiology)
• HL-60 Cells
• Humans
• Leukemia, Promyelocytic, Acute (drug therapy, pathology)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Xenograft Model Antitumor Assays (methods)