In this revised Program Project renewal application, the applicant group is representative of three primary institutions. The Ohio State University (OSU), the University of Illinois at Chicago (UIC), and the University of North Carolina at Greensboro (UNCG). The participants have combined their vast experience in the isolation, structure elucidation, and biological evaluation of natural products, to continue the development of a consolidated, integrated program for the discovery of novel anticancer agents of diverse origin for development as cancer chemotherapeutic agents. Plant materials to be studied in Project 1 (OSU) will be collected by established botanists located in tropical countries with the assistance of the NAPRALERT database (Project 2;UIC), and cyanobacteria (Project 2) and filamentous fungi (Project 3 UNCG) will also be accessed. Organisms acquired will be extracted and evaluated in a diverse battery of relevant mechanism-based, cell-based, and tumor-growth related assays currently operational at OSU (Project 1), UIC (Core A), Columbia University (through Project 3), and a new pharmaceutical company partner, Eisai Inc., Andover, MA (through Core C at OSU). Dereplication of known active compounds will be accomplished at OSU, UIC, and UNCG using computerized literature surveys and LC-MS coupled to bioassays. Bioassay-directed fractionation will be employed in Projects 1-3, for the elucidation of active principles. Lead development of active natural products via medicinal chemistry and pharmacokineticsrelated studies will be conducted at OSU (Core B), facilitated by the OSU Biostatistics group (Core C). Novel, active compounds thus discovered will be further evaluated in our panel of in vitro and in vivo bioassays (Projects 1 and 3, Cores A and Eisai). Group decisions will be made regarding the further development of agents for potential use as anticancer agents. The more advanced states of biological and toxicological testing, as well as the procurement of larger quantities of lead compounds will be sponsored by Eisai (through Core C). The Consortium will work with the involvement of the NCI Program Director in the discovery process, and plans to hold regular meetings of key scientific personnel (inclusive of our External and OSU Internal Advisory panels) to enhance communication and decision-making processes, to be organized by Core C. Excellent facilities for the isolation, structure determination, chemical modification, synthesis, and in vitro and in vivo biological evaluation, and overall project data management are available.

Public Health Relevance

Cancer is responsible for about one in every four deaths in the United States, and new treatments are urgently needed. It is the overall goal of the integrated studies in this renewal application to discover novel chemicals from selected tropical rainforest plants, as well as cyanobacteria and fungi, for development as cancer chemotherapeutic agents, particularly for tumors not cured by present treatment methods.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
2P01CA125066-06A1
Application #
8608726
Study Section
Special Emphasis Panel (ZCA1-RPRB-C (O1))
Program Officer
Fu, Yali
Project Start
2006-12-01
Project End
2019-04-30
Budget Start
2014-06-06
Budget End
2015-04-30
Support Year
6
Fiscal Year
2014
Total Cost
$1,484,104
Indirect Cost
$247,118
Name
Ohio State University
Department
Type
Schools of Pharmacy
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
Ren, Yulin; Chen, Wei-Lun; Lantvit, Daniel D et al. (2016) Cardiac Glycoside Constituents of Streblus asper with Potential Antineoplastic Activity. J Nat Prod :
Guo, Brian; Onakpa, Monday M; Huang, Xiao-Jun et al. (2016) Di-nor- and 17-nor-pimaranes from Icacina trichantha. J Nat Prod 79:1815-21
Chen, Wei-Lun; Pan, Li; Kinghorn, A Douglas et al. (2016) Silvestrol induces early autophagy and apoptosis in human melanoma cells. BMC Cancer 16:17
Ren, Yulin; Yu, Jianhua; Kinghorn, A Douglas (2016) Development of Anticancer Agents from Plant-Derived Sesquiterpene Lactones. Curr Med Chem 23:2397-420
Muñoz Acuña, Ulyana; Carcache, Peter J Blanco; Matthew, Susan et al. (2016) New acyclic bis phenylpropanoid and neolignans, from Myristica fragrans Houtt., exhibiting PARP-1 and NF-κB inhibitory effects. Food Chem 202:269-75
Othman, Nuraqilah; Pan, Li; Mejin, Michele et al. (2016) Cyclopenta[b]benzofuran and Secodammarane Derivatives from the Stems of Aglaia stellatopilosa. J Nat Prod 79:784-91
Kinghorn, A Douglas; DE Blanco, Esperanza J Carcache; Lucas, David M et al. (2016) Discovery of Anticancer Agents of Diverse Natural Origin. Anticancer Res 36:5623-5637
Ren, Yulin; Benatrehina, P Annécie; Muñoz Acuña, Ulyana et al. (2016) Isolation of Bioactive Rotenoids and Isoflavonoids from the Fruits of Millettia caerulea. Planta Med 82:1096-104
Alali, Feras; El-Elimat, Tamam; Albataineh, Hanan et al. (2015) Cytotoxic Homoisoflavones from the Bulbs of Bellevalia eigii. J Nat Prod 78:1708-15
Zhao, Ming; Onakpa, Monday M; Santarsiero, Bernard D et al. (2015) (9βH)-Pimaranes and Derivatives from the Tuber of Icacina trichantha. J Nat Prod 78:2731-7

Showing the most recent 10 out of 113 publications