title: An in vivo molecular response analysis of colorectal cancer treated with Astragalus membranaceus extract.
abstract: The fact that many chemotherapeutic drugs cause chemoresistance and side effects during the course of colorectal cancer treatment necessitates development of novel cytotoxic agents aiming to attenuate new molecular targets. Here, we show that Astragalus membranaceus (Fischer) Bge. var. mongolicus (Bge.) Hsiao (AM), a traditional Chinese medicine, can inhibit tumor growth in vivo and elucidate the underlying molecular mechanisms. The antitumor effect of AM was assessed on the subcutaneous tumors of human colorectal cancer cell line HCT116 grafted into nude mice. The mice were treated with either water or 500 mg/kg AM once per day, before being sacrificed for extraction of tumors, which were then subjected to microarray expression profiling. The gene expression of the extraction was then profiled using microarray analysis. The identified genes differentially expressed between treated mice and controls reveal that administration of AM suppresses chromosome organization, histone modification, and regulation of macromolecule metabolic process. A separate analysis focused on differentially expressed microRNAs revealing involvement of macromolecule metabolism, and intracellular transport, as well as several cancer signaling pathways. For validation, the input of the identified genes to The Library of Integrated Network-based Cellular Signatures led to many chemopreventive agents of natural origin that produce similar gene expression profiles to that of AM. The demonstrated effectiveness of AM suggests a potential therapeutic drug for colorectal cancer.
authors.affiliation: Institute of Systems Biology and Bioinformatics, National Central University, Taoyuan 320, Taiwan, R.O.C.
authors.forename: Ailun
authors.initials: A
authors.lastname: Tseng
authors.affiliation: Graduate Institute of Microbiology and Public Health, National Chung Hsing University, Taichung 402, Taiwan, R.O.C.
authors.forename: Chih-Hsueh
authors.initials: CH
authors.lastname: Yang
authors.affiliation: Institute of Systems Biology and Bioinformatics, National Central University, Taoyuan 320, Taiwan, R.O.C.
authors.forename: Chih-Hao
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan, R.O.C.
authors.forename: Chang-Han
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Department of Education and Research, Taichung Veterans General Hospital, Taichung 407, Taiwan, R.O.C.
authors.forename: Shih-Lan
authors.initials: SL
authors.lastname: Hsu
authors.affiliation: Graduate Institute of Pharmacognosy, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan, R.O.C.
authors.forename: Mei-Hsien
authors.initials: MH
authors.lastname: Lee
authors.affiliation: Center for Dynamical Biomarkers and Translational Medicine, National Central University, Taoyuan 320, Taiwan, R.O.C.
authors.forename: Hoong-Chien
authors.initials: HC
authors.lastname: Lee
authors.affiliation: Institute of Systems Biology and Bioinformatics, National Central University, Taoyuan 320, Taiwan, R.O.C.
authors.forename: Li-Jen
authors.initials: LJ
authors.lastname: Su
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D027885:Astragalus propinquus; D015179:Colorectal Neoplasms / Q000473:pathology*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D045325:HCT116 Cells; D006801:Humans; D008297:Male; D008516:Medicine, Chinese Traditional; D051379:Mice; D008819:Mice, Nude; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal