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http://ir.nhri.org.tw/handle/3990099045/9773
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| Title: | Active fraction of Taiwanofungus camphoratus (HS7) exerted anticancer effects through multiple molecule targeting and elimination of cancer stem-like cells in lung cancer and hepatoma cells |
| Authors: | Lai, GM;Yao, CJ;Yeh, CT;Yeh, CF;Chang, CK;Yan, JL;Li, CH;Chuang, SE |
| Contributors: | National Institute of Cancer Research |
| Abstract: | Objective: Taiwanofungus camphoratus (Antrodia camphorata), a unique Taiwan folk medicine, has been shown possessing the effects of antioxidation, vasorelaxtation, anti-inflammation, anti-hepatitis and anticancer. However, little has been known about the precise mechanisms responsible for anticancer effect. In this study, we would like to investigate the molecular mechanisms underlying the anticancer effects of its partially purified active fraction HS7. Materials and Methods: The cultivated Taiwanofungus camphoratus powder was extracted by n-hexane and further separated by silica gel to get HS7 fraction. Human hepatoma (Huh7) and lung adenocarcinoma (CL1-0 and A549) cell lines were used in this study. The cell proliferation and colony formation ability were determined by sulforhodamine B and amido black staining, respectively. Western blot and antibodies against specific phosphorylated proteins were employed to analyze the activities of affected signaling pathways. The mRNA expression was analyzed by RT-PCR. The cell cycle was analyzed by flow cytometry and the cancer stem-like side population (SP) cells were isolated by UV laser-equipped flow cytometer FACSaria. Results: The active fraction HS7 substantially inhibited the growth of CL1-0 cells accompanied with the increase of p15, p21 and p27 CDK inhibitors. In the aspect of its effects on oncogenic signaling pathways, HS7 dose-dependently inhibited the Akt/mTOR/p-70S6k, Stat3, MEK/ERK pathways and decreased the HIF-1\#945; and phosphorylated form of Rac1 protein, respectively. On the other hand, a small percentage of SP cells with characteristics of cancer stem cells were successfully sorted from Huh7 and A549 cell lines. In comparison with the non-SP cells, the SP cells appeared to have higher clonogenicity and expressed much more mRNA levels of stem cell surface marker (CD133), Hedgehog and Wnt signaling molecules (\#946;-catenin and SMO) as well as drug resistance associated ATP binding cassette transporter ABCG2. After treatment with HS7 (25 \#956;g/ml), the percentage of SP cells was decreased from 1.69% to 0.53% in Huh7 cells and from 1.79% to 0.18% in A549 cells, respectively. Moreover, the clonogenicity and the mRNA expressions of ABCG2, \#946;-catenin and SMO in these SP cells were all decreased by HS7 in a dose-dependent manner.Conclusion: Our results demonstrated that the active fraction (HS7) possessed multiple molecular targeting anticancer effects, including the cell-cycle regulation and the inhibition of oncogenic signaling pathways. The elimination of cancer stem-like cells by HS7 may bring a new insight of integrative cancer therapy. |
| Date: | 2009-05 |
| Relation: | Cancer Research. 2009 May;69:Abstract number 5475. |
| Link to: | http://cancerres.aacrjournals.org/content/69/9_Supplement/5475.short |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0008-5472&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000209702704482 |
| Appears in Collections: | [莊雙恩] 會議論文/會議摘要
[賴基銘(2004-2008)] 會議論文/會議摘要
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| ISI000209702704482.pdf | | 18Kb | Adobe PDF | 417 | View/Open |
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