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1 May 2013
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Melanoma, the most aggressive form of skin cancer, accounts for 75% of skin cancer mortality. The activation of the signaling cascade comprising BRAF-NRAS-MEK1/2-ERK1/2 is an important trigger for melanoma survival, growth and proliferation. Several studies have demonstrated the chemopreventive and/or chemotherapeutic effects of silybin, a major bioactive component of milk thistle (Silybum marianum), against various cancers. Virtual screening revealed that silybin is a potent inhibitor of the BRAF-MEK-ERK-RSK2 signaling pathway. The direct binding of silybin with RSK2 (ribbon structure shown) and MEK1/2 (not shown) was generated using the Schrödinger Induced Fit docking program. Silybin was shown to significantly inhibit melanoma cell growth in vitro and in vivo through its direct binding with MEK1/2 and RSK2, resulting in the inhibition of their catalytic kinase activities and subsequent reduction in the activation of NF-kB, AP-1 and STAT3—transcriptional regulators of a variety of proliferative genes in melanomas. See article by Lee and colleagues (beginning on page 455) for more information. - PDF Icon PDF LinkTable of Contents
ISSN 1940-6207
EISSN 1940-6215
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Commentary
Perspective
Reviews
Research Articles
Bowman Birk Inhibitor Concentrate and Oral Leukoplakia: A Randomized Phase IIb Trial
William B. Armstrong; Thomas H. Taylor; Ann R. Kennedy; Raymond J. Melrose; Diana V. Messadi; Mai Gu; Anh D. Le; Marjorie Perloff; Francisco Civantos; William Jarrard Goodwin; Lori J. Wirth; Alexander Ross Kerr; Frank L. Meyskens, Jr
Increased Levels of Urinary PGE-M, a Biomarker of Inflammation, Occur in Association with Obesity, Aging, and Lung Metastases in Patients with Breast Cancer
Patrick G. Morris; Xi Kathy Zhou; Ginger L. Milne; Daniel Goldstein; Laura C. Hawks; Chau T. Dang; Shanu Modi; Monica N. Fornier; Clifford A. Hudis; Andrew J. Dannenberg
Association of Tooth Loss and Oral Hygiene with Risk of Gastric Adenocarcinoma
Ramin Shakeri; Reza Malekzadeh; Arash Etemadi; Dariush Nasrollahzadeh; Behnoush Abedi-Ardekani; Masoud Khoshnia; Farhad Islami; Akram Pourshams; Michael Pawlita; Paolo Boffetta; Sanford M. Dawsey; Farin Kamangar; Christian C. Abnet
Curcumin-Targeting Pericellular Serine Protease Matriptase Role in Suppression of Prostate Cancer Cell Invasion, Tumor Growth, and Metastasis
Tai-Shan Cheng; Wen-Chi Chen; Ya-Yun Lin; Chin-Hsien Tsai; Chia-I Liao; Hsin-Yi Shyu; Chun-Jung Ko; Sheue-Fen Tzeng; Chun-Yin Huang; Pan-Chyr Yang; Pei-Wen Hsiao; Ming-Shyue Lee
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