title: Withanone-rich combination of Ashwagandha withanolides restricts metastasis and angiogenesis through hnRNP-K.
abstract: Ashwagandha is an important herb used in the Indian system of traditional home medicine, Ayurveda. Alcoholic extract (i-Extract) from its leaves and its component, withanone, were previously shown to possess anticancer activity. In the present study, we developed a combination of withanone and withaferin A, major withanolides in the i-Extract, that retained the selective cancer cell killing activity and found that it also has significant antimigratory, -invasive, and -angiogenic activities, in both in vitro and in vivo assays. Using bioinformatics and biochemical approaches, we demonstrate that these phytochemicals caused downregulation of migration-promoting proteins hnRNP-K, VEGF, and metalloproteases and hence are candidate natural drugs for metastatic cancer therapy.
authors.affiliation: Cell Proliferation Research Group and DBT-AIST International Laboratory for Advanced Biomedicine, National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, Ibaraki, Japan.
authors.forename: Ran
authors.initials: R
authors.lastname: Gao
authors.affiliation: Cell Proliferation Research Group and DBT-AIST International Laboratory for Advanced Biomedicine, National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, Ibaraki, Japan.
authors.forename: Navjot
authors.initials: N
authors.lastname: Shah
authors.affiliation: Department of Bioengineering, College of Engineering, Hanyang University, Seongdong-Gu, Seoul, Korea.
authors.forename: Jung-Sun
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Biochemical Engineering & Biotechnology, Indian Institute of Technology (IIT) Delhi, Hauz Khas, New Delhi, India.
authors.forename: Shashank P
authors.initials: SP
authors.lastname: Katiyar
authors.affiliation: Cell Proliferation Research Group and DBT-AIST International Laboratory for Advanced Biomedicine, National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, Ibaraki, Japan.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Bioengineering, College of Engineering, Hanyang University, Seongdong-Gu, Seoul, Korea.
authors.forename: Eonju
authors.initials: E
authors.lastname: Oh
authors.affiliation: Department of Biochemical Engineering & Biotechnology, Indian Institute of Technology (IIT) Delhi, Hauz Khas, New Delhi, India.
authors.forename: Durai
authors.initials: D
authors.lastname: Sundar
authors.affiliation: Department of Bioengineering, College of Engineering, Hanyang University, Seongdong-Gu, Seoul, Korea. renu-wadhwa@aist.go.jp s-kaul@aist.go.jp chaeok@hanyang.ac.kr.
authors.forename: Chae-Ok
authors.initials: CO
authors.lastname: Yun
authors.affiliation: Cell Proliferation Research Group and DBT-AIST International Laboratory for Advanced Biomedicine, National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, Ibaraki, Japan. renu-wadhwa@aist.go.jp s-kaul@aist.go.jp chaeok@hanyang.ac.kr.
authors.forename: Renu
authors.initials: R
authors.lastname: Wadhwa
authors.affiliation: Cell Proliferation Research Group and DBT-AIST International Laboratory for Advanced Biomedicine, National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, Ibaraki, Japan. renu-wadhwa@aist.go.jp s-kaul@aist.go.jp chaeok@hanyang.ac.kr.
authors.forename: Sunil C
authors.initials: SC
authors.lastname: Kaul
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D034641:Heterogeneous-Nuclear Ribonucleoprotein K / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D010936:Plant Extracts / Q000737:chemistry*; D015203:Reproducibility of Results; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*; D047368:Tumor Burden / Q000187:drug effects; D054358:Withanolides / Q000737:chemistry / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D010936:Plant Extracts; D014315:Triterpenes; D054358:Withanolides; C560597:withanone; C009684:withaferin A; C030693:Ashwagandha