caa a22 4500 606235604 CHVBK 20210128101243.0 cr unu---uuuuu 210128e20150901xx s 000 0 eng 10.1007/s11010-015-2471-6 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2471-6 Myricetin induces apoptosis by inhibiting P21 activated kinase 1 (PAK1) signaling cascade in hepatocellular carcinoma [Elektronische Daten] [Soumya Iyer, Ashidha Gopal, Devaraj Halagowder] Hepatocellular carcinoma is one of the most common malignancies worldwide and evidence suggests that Ras signaling regulates various hallmarks of cancer via regulating several effector pathways such as ERK and PI3K. The aim of the present study is to understand the efficacy of a flavonoid myricetin for the first time in inhibiting the downstream target p21 activated kinase 1 (PAK1) of Ras signaling pathway in hepatocellular carcinoma. The analysis of gene expression revealed that myricetin inhibits PAK1 by abrogating the Ras-mediated signaling by decelerating Wnt signaling, the downstream of Erk/Akt, thereby inducing intrinsic caspase-mediated mitochondrial apoptosis by downregulating the expression of anti-apoptotic Bcl-2 and survivin and upregulating pro-apoptotic Bax. The results also provide striking evidence that the myricetin inhibits the development of HCC by inhibiting PAK1 via coordinate abrogation of MAPK/ERK and PI3K/AKT and their downstream signaling Wnt/β-catenin pathway, thus being a promising candidate for cancer prevention and therapy. Springer Science+Business Media New York, 2015 PAK1 nationallicence Myricetin nationallicence Erk1/2 nationallicence β-Catenin nationallicence Iyer Soumya Unit of Biochemistry, Department of Zoology, School of Life Sciences, University of Madras, Guindy Campus, 600025, Chennai, Tamil Nadu, India aut Gopal Ashidha Unit of Biochemistry, Department of Zoology, School of Life Sciences, University of Madras, Guindy Campus, 600025, Chennai, Tamil Nadu, India aut Halagowder Devaraj Unit of Biochemistry, Department of Zoology, School of Life Sciences, University of Madras, Guindy Campus, 600025, Chennai, Tamil Nadu, India aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 407/1-2(2015-09-01), 223-237 0300-8177 407:1-2<223 2015 407 11010 https://doi.org/10.1007/s11010-015-2471-6 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2471-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Iyer Soumya Unit of Biochemistry, Department of Zoology, School of Life Sciences, University of Madras, Guindy Campus, 600025, Chennai, Tamil Nadu, India aut NATIONALLICENCE 700 1- Gopal Ashidha Unit of Biochemistry, Department of Zoology, School of Life Sciences, University of Madras, Guindy Campus, 600025, Chennai, Tamil Nadu, India aut NATIONALLICENCE 700 1- Halagowder Devaraj Unit of Biochemistry, Department of Zoology, School of Life Sciences, University of Madras, Guindy Campus, 600025, Chennai, Tamil Nadu, India aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 407/1-2(2015-09-01), 223-237 0300-8177 407:1-2<223 2015 407 11010