Antrodia camphorata extract induces replicative senescence in superficial TCC, and inhibits the absolute migration capability in invasive bladder carcinoma cells Chiung-Chi Peng a,b,1, Kuan-Chou Chena,c,1, Robert Y. Peng a,d, Charng-Cherng Chyaud, Ching-Hua Sua,e, Hsiu Mei Hsieh-Li a,f,∗
a Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, 250 Wu-Xing Street, Taipei 110, Taiwan b Department of Nursing, Cardinal Tien College of Nursing, No. 364, Chung Cheng Road, Hsintien City, Taipei Hsien 23148, Taiwan c Department of Urology, Taipei Medical University Hospital, Taipei Medical University, 250 Wu-Xing Street, Taipei 110, Taiwan d Research Institute of Medicinal Science and Technology, Hung-Kuang University, No. 34, Chun-Chie Road, Shalu City, Taichung Hsien 43302, Taiwan e Graduate Institute of Biomedical Material, Taipei Medical University, No. 250, Wu-Xing Street, Taipei 110, Taiwan f Department of Life Science, National Taiwan Normal University, 88, Sec. 4, Ting-Chou Road, Taipei 116, Taiwan
Abstract The Antrodia camphorata crude extract (ACCE), an extract obtained from a precious traditional Chinese folkloric herbal medicine Zhan-Ku (a camphor tree mushroom) since the 18th century, has showed rather significant inhibitory effects on the growth and proliferation of the transitional cell carcinomas (TCC) cell lines RT4, TSGH-8301, and T24. On treatment with ACCE at 100 g/mL, the p53-independent overexpression of p21 with simultaneous down alteration of pRbwas observed inRT4, whichwas thus speculative of proceeding through a mechanism of replicative senescence. On the contrary treatment with ACCE, at 50 g/mL, resulting in simultaneous down-regulations of Cdc2 and Cyclin B1, with suppression of the absolute migrating capability of the two cell lines TSGH-8301 and T24, and eventually the cell deaths. We conclude that ACCE can be rather effective and beneficial in suppression of both the superficial cancer cell line RT4 and the metastatic cell lines (TSGH-8301 and T24) through different mechanisms.
Inhibition of Anchorage-Independent Proliferation and G0/G1 Cell-Cycle Regulation in Human Colorectal Carcinoma Cells by 4,7-Dimethoxy-5-Methyl-l,3-Benzodioxole Isolated from the Fruiting Body of Antrodia camphorate
1Department of Chemistry, Tunghai University, Taichung, Taiwan 2Graduate Institute of Biomedical Technology, Taipei Medical University, Taipei 110, Taiwan 3Department of Environmental and Occupational Health, National Cheng Kung University Medical College, Tainan, Taiwan 4Graduate Institute of Neuroscience, Taipei Medical University, Taipei, Taiwan 5Department of Applied Chemistry, Chung Shan Medical University, Taichung 402, Taiwan
In this study, 4,7-dimethoxy-5-methyl-l,3-benzodioxole (SY-1) was isolated from three different sources of dried fruiting bodies of Antrodia camphorate (AC). AC is a medicinal mushroom that grows on the inner heartwood wall of Cinnamomum kanehirai Hay (Lauraceae), an endemic species that is used in Chinese medicine for its anti-tumor and immunomodulatory properties. In this study, we demonstrated that SY-1 profoundly decreased the proliferation of human colon cancer cells (COLO 205) through G0/G1 cell-cycle arrest (50–150 μM) and induction of apoptosis (>150 μM). Cell-cycle arrest induced by SY-1 was associated with a significant increase in levels of p53, p21/Cip1 and p27/Kip1, and a decrease in cyclins D1, D3 and A. In contrast, SY-1 treatment did not induce significant changes in G0/G1 phase cell-cycle regulatory proteins in normal human colonic epithelial cells (FHC). The cells were cultured in soft agar to evaluate anchorage-independent colony formation, and we found that the number of transformed colonies was significantly reduced in the SY-1-treated COLO 205 cells. These findings demonstrate for the first time that SY-1 inhibits human colon cancer cell proliferation through inhibition of cell growth and anchorage-independent colony formation in soft agar. However, the detailed mechanisms of these processes remain unclear and will require further investigation.
Source : Evidence-Based Complementary and Alternative Medicine Volume 2011 (2011), Article ID 984027, 10 pages doi:10.1093/ecam/nep020 Link to Full Article
Human urinary bladder cancer T24 cells are susceptible to the Antrodia camphorata extracts Chiung-Chi Peng a, Kuan-Chou Chen a,b, Robert Y. Peng c, Ching-Hua Su a,d, Hsiu Mei Hsieh-Li a,e,*
a Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC b Department of Urology, Taipei Medical University Hospital, Taipei, Taiwan, ROC c Research Institute of Biotechnology, Hung-Kuang University, Taichung, Taiwan d Graduate Institute of Biomedical Material, Taipei Medical University, Taipei, Taiwan, ROC e Department of Life Science, National Taiwan Normal University, 88, Sec. 4, Ting-Chou Road, Taipei 116, Taiwan, ROC
Abstract Bladder cancer has been cited to result from the neoplastic lesion with environmental and/or occupational factors identified as causatives. Transitional cell carcinoma (TCC) is the most common type of bladder cancer. Most of the bladder cancer patients die from the invasive, metastatic TCC that has turned out to be resistant to chemotherapy. T24 cells, a cell line established from a human urinary bladder cancer patient, are high-grade and invasive TCC. T24 cells were found very susceptible to ACCE at concentration of 50 mg/mL. MTT assay showed that the cell growth and proliferation were inhibited to 50% of the control when treated with ACCE for 72 h, at which the cell proliferation suppressing rate revealed K4.4!103 cells/mg per day. Comparing the expressions of the cell cycle biomarkers Cdc2 and Cyclin B1 by the western blot analysis, a phase G2M arrest was confirmed. Both the wound scratch assay and the transwell motility assay indicated that ACCE was very effective anti-metastatic against T24 cells. Furthermore, the active form of matrix metalloproteinase-9 (MMP-9) was also found totally suppressed as revealed by zymography at 72 h post-incubation with ACCE, while the light and electron microscopic images have apparently revealed cell membrane damages on T24 cells when treated with ACCE (50 mg/mL). Moreover, both the wound scratch and the transwell assays have demonstrated the migration capability of T24 cells has been significantly retarded to 1.5-fold at same dosage of ACCE used. In conclusion, ACCE is a good anti-cancer agent, being effective in inducing phase G2M arrest, acting as an anti-proliferative, and an anti-metastatic agent against bladder cancer cell T24 cells.