Dryopteris crassirhizoma has anti-cancer effects through both extrinsic and intrinsic apoptotic pathways and G0/G1 phase arrest in human prostate cancer cells |
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Authors: | Sung-Ho Chang Jae-Ho Bae Doo-Pyo Hong Kang-Duk Choi Song-Cheol Kim Erk Her Sun-Hee Kim Chi-Dug Kang |
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Institution: | 1. BK21 Medical Science Education Center, Department of Biochemistry, Pusan National University School of Medicine, Yangsan-City, Gyeongsangnam-do 626-770, Republic of Korea;2. Department of Immunology, College of Medicine, Konkuk University, Chungju-City 380-701, Republic of Korea;3. Gyeong-gi Regional Research Center, Hankyong National University, Ansung-City, Gyeonggi-do 456-749, Republic of Korea;4. Samsung Biomedical Research Institute, Gangnam-gu, Seoul 135-710, Republic of Korea;5. Department of Surgery and Asan Institute for Life Sciences, Ulsan University College of Medicine & Asan Medical Center, Songpa-gu, Seoul 138-736, Republic of Korea |
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Abstract: | Aim of the studyThe inhibitory effect of Dryopteris crassirhizoma on the proliferation of human metastatic prostate PC3-MM2 cells and the mechanism of action were examined to identify its anti-cancer properties. The effect of the extract on cell cycle progression and its combined cytotoxic effect with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on PC3-MM2 cells were also investigated.Materials and methodsThe anti-proliferative effects of Dryopteris crassirhizoma were examined by culturing PC3-MM2 cells in the presence or absence of various concentrations of Dryopteris crassirhizoma extract, and the inhibitory effects on cell proliferation were determined by Cell Counting Kit (CCK)-8 analysis. The quantities of apoptosis-inducing proteins were measured by western blotting analysis. Cell cycle progression was analyzed by PI staining using flow cytometry.ResultsDryopteris crassirhizoma (50 and 100 μg/ml) inhibited markedly the proliferation of PC-3 and PC3-MM2 cells without cytotoxicity to normal (spleen) cells from BALB/C mice. Dryopteris crassirhizoma (100 μg/ml) effectively induced apoptosis through the activation of caspase-3, -8, -9, bid, and PARP in PC3-MM2 cells. The cells exposed to Dryopteris crassirhizoma increased significantly the accumulation of the DNA contents in the G0/G1 phase and sub-G1 phase in contrast to the control. The combined cytotoxic effects of Dryopteris crassirhizoma and TRAIL induced the increased activity of 29% in contrast to the sum of the inhibitory effects of each agent alone.ConclusionsDryopteris crassirhizoma has anti-cancer properties by inducing cell cycle arrest and apoptosis through the extrinsic and intrinsic pathway in PC3-MM2 cells. The extract also showed a combined effect with TRAIL on the inhibition of proliferation in the cells. These findings suggest that possibly its extract could be used for treating androgen-independent prostate cancer with minimal side effects. |
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Keywords: | Dryopteris crassirhizoma Aspidiaceae Prostate cancer Anti-cancer Caspase Cell cycle arrest TRAIL |
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