You-Cheng Hseu1, Chuan-Chen Lee2, Yung-Chang Chen3, K J Senthil Kumar4, Chee-Shan Chen3, Yu-Chi Huang5, Li-Sung Hsu6, Hui-Chi Huang7, Hsin-Ling Yang8. 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.
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 humanpromyelocytic 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 humanpromyelocytic leukemia.