title: Identification of potential anticancer compounds from Oplopanax horridus.
abstract: Oplopanax horridus is a plant native to North America. Previous reports have demonstrated that this herb has antiproliferative effects on cancer cells but study mostly focused on its extract or fractions. Because there has been limited phytochemical study on this herb, its bioactive compounds are largely unknown. We recently isolated and identified 13 compounds, including six polyynes, three sesquiterpenes, two steroids, and two phenolic acids, of which five are novel compounds. In this study, we systemically evaluated the anticancer effects of compounds isolated from O. horridus. Their antiproliferative effects on a panel of human colorectal and breast cancer cells were determined using the MTS assay. Cell cycle distribution and apoptotic effects were analyzed by flow cytometry. The in vivo antitumor effect was examined using a xenograft tumor model. Among the 13 compounds, strong antiproliferative effects were observed from falcarindiol and a novel compound oplopantriol A. Falcarindiol showed the most potent antiproliferative effects, significantly inducing pro-apoptosis and cell cycle arrest in the S and G2/M phases. The anticancer potential of falcarindiol was further verified in vivo, significantly inhibiting HCT-116 tumor growth in an athymic nude mouse model at 15 mg/kg. We also analyzed the relationship between polyyne structures and their pharmacological activities. We observed that both the terminal hydroxyl group and double bond obviously affected their anticancer potential. Results from this study supplied valuable information for future semi-synthesis of polyyne derivatives to develop novel cancer chemopreventive agents.
authors.affiliation: Tang Center for Herbal Medicine Research, and Department of Anesthesia & Critical Care, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Chong-Zhi
authors.initials: CZ
authors.lastname: Wang
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Zhang
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Huang
authors.forename: Guang-Jian
authors.initials: GJ
authors.lastname: Du
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Wen
authors.forename: Tyler
authors.initials: T
authors.lastname: Calway
authors.forename: Chunhao
authors.initials: C
authors.lastname: Yu
authors.forename: Rachael
authors.initials: R
authors.lastname: Nass
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Wei
authors.initials: W
authors.lastname: Du
authors.forename: Shao-Ping
authors.initials: SP
authors.lastname: Li
authors.forename: Chun-Su
authors.initials: CS
authors.lastname: Yuan
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D053280:Diynes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D005233:Fatty Alcohols / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D064593:Heterografts; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D028002:Oplopanax / Q000737:chemistry*; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D053280:Diynes; D005233:Fatty Alcohols; D010936:Plant Extracts; C034379:falcarindiol
keywords: Anticancer; Apoptosis; Cell cycle; Falcarindiol; Oplopanax horridus; Oplopantriol A; Phytochemistry; Polyynes; Structure–activity relationship