title: Differential effects of grape seed extract against human colorectal cancer cell lines: the intricate role of death receptors and mitochondria.
abstract: Failure of anti-cancer therapy in colorectal cancer (CRC) cells involves resistance to death mechanisms. We investigated grape seed extract (GSE) ability to target CRC cells and delineated the mechanisms involved in GSE-induced CRC cell death. GSE selectively induced apoptotic death in human CRC cells; efficacy increased as the metastatic potential of the cancer cells increased. Oxidative stress, loss of mitochondrial membrane potential, modulation of pro- and anti-apoptotic proteins, and involvement of both caspase-dependent/independent apoptotic pathways contributed to GSE-induced CRC cell death. GSE intervention may serve as a multi-targeted CRC therapeutic capable of inducing selective cancer cell death.
authors.affiliation: Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: Molly
authors.initials: M
authors.lastname: Derry
authors.affiliation: Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: Komal
authors.initials: K
authors.lastname: Raina
authors.affiliation: Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Agarwal
authors.affiliation: Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA. Electronic address: Chapla.Agarwal@UCDenver.edu.
authors.forename: Chapla
authors.initials: C
authors.lastname: Agarwal
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004354:Drug Screening Assays, Antitumor; D016158:Genes, p53; D056604:Grape Seed Extract / Q000494:pharmacology*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D056604:Grape Seed Extract; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D020169:Caspases