Dryopteris crassirhizoma has anti-cancer effects through both extrinsic and intrinsic apoptotic pathways and G0/G1 phase arrest in human prostate cancer cells

• Published in: Journal of ethnopharmacology 2010-07, Vol.130 (2), p.248-254
• Main Authors: Chang, Sung-Ho, Bae, Jae-Ho, Hong, Doo-Pyo, Choi, Kang-Duk, Kim, Song-Cheol, Her, Erk, Kim, Sun-Hee, Kang, Chi-Dug
• Format: Article
• Language: English
• Subjects: Animals; Anti-cancer; anticarcinogenic activity; antineoplastic agents; Antineoplastic Agents, Phytogenic - pharmacology; Antineoplastic Agents, Phytogenic - toxicity; apoptosis; Apoptosis - drug effects; Aspidiaceae; BH3 Interacting Domain Death Agonist Protein - metabolism; biochemical pathways; Biological and medical sciences; Blotting, Western; Caspase; Caspases - metabolism; cell cycle; Cell Cycle - drug effects; Cell cycle arrest; Cell Line, Tumor; cell proliferation; Cell Proliferation - drug effects; cytotoxicity; Dose-Response Relationship, Drug; drug evaluation; Drug Synergism; Dryopteris; Dryopteris crassirhizoma; Flow Cytometry; G1 Phase; Gas Chromatography-Mass Spectrometry; General pharmacology; human cell lines; Humans; in vitro studies; inhibitors; Male; Medical sciences; medicinal plants; metastasis; Mice; Mice, Inbred BALB C; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Poly(ADP-ribose) Polymerases - metabolism; Prostate cancer; prostatic neoplasms; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Resting Phase, Cell Cycle; Time Factors; TNF-Related Apoptosis-Inducing Ligand - pharmacology; TRAIL; tumor necrosis factors
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2010.04.038

The 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. The 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. Dryopteris 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. Dryopteris 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.