Proapoptotic and TRAIL-sensitizing constituents isolated from Salvia militiorrhiza (Danshen)(BIOMEDICAL ENGINEERING)

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概要

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• Natural compounds isolated from medicinal plants are invaluable resources for drug discovery. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent unique by its cancer cell-specific proapoptotic action, but its potential is heavily curbed by acquired resistance. We herein reported for the first time the identification of cytotoxic and TRAIL-sensitizing components of Salvia miltiorrhiza (Danshen), a traditional medicinal plant effective for treating cardiovascular disorders. Specifically, we found that the ethanol extract and its group 5 fraction of S. miltiorrhiza showed evident cytotoxicity against the human lung adenocarcinoma cell line A549 and ovarian adenocarcinoma cell line TOV-21G in a concentration-dependent manner. Likewise, a dose-dependent cytotoxicity was exerted by the standard solutions of cryptotanshinone, tanshinone I and tanshinone IIA, the major components of the group 5 fraction, where tanshinone IIA were most potent and displayed an IC_<50> of 2.00 ± 0.36 μM and 2.75 ± 0.23 Rail for A549 and TOV-21G, respectively. Induction of apoptosis represents an essential mechanism underlying tanshinone IIA-mediated cytotoxic action, as evidenced by the proteolytic processing of PARP upon tanshinone IIA stimulation and, importantly, a marked rescue of the viability of tanshinone IIA-treated cells when co-treatment with the pan-caspase inhibitor z-VAD-fmk. Noteworthy, stimulation with cryptotanshinone, tanshinone I or tanshinone IIA all effectively potentiated TRAIL to reduce viability and inhibit the colony formation capacity of TRAIL-resistant TOV-21G and SKOV3. Collectively, we revealed the proapoptotic and TRAIL-sensitizing components of S. miltiorrhiza and further implicated the potential of developing these active compounds as monotherapeutic agent or TRAIL-based therapy for cancer chemoprevention or chemotherapy.

著者

• Ho Tsing-fen

  Department Of Medical Laboratory Science And Biotechnology Central Taiwan University Of Science And

• Chang Chia-che

  Institute Of Biomedical Sciences National Chung Hsing University:graduate Institute Of Basic Medical

• Lu Chien-Hsing

  Department of Obstetrics and Gynecology, Taichung Veterans General Hospital:Department of Obstetrics and Gynecology, National Yang-Ming University School of Medicine

• Lai Jui-Sheng

  Division of Biotechnology, Taiwan Agricultural Research Institute

• Tsai Chi-Shiuan

  Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology

• Huang Lan-Ru

  Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology

• Lin Jyun-Yi

  Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology

• Ma Song-Wei

  Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology:Institute of Biomedical Sciences, National Chung Hsing University

• Liao En-Chih

  Department of Medical Research and Education, Taichung Veterans General Hospital

関連論文

• Development of natural anti-tumor drugs by microorganisms
• Proapoptotic and TRAIL-sensitizing constituents isolated from Salvia militiorrhiza (Danshen)(BIOMEDICAL ENGINEERING)

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