title: Augmenting anti-cancer natural products with a small molecule adjuvant.
abstract: Aquatic microbes produce diverse secondary metabolites with interesting biological activities. Cytotoxic metabolites have the potential to become lead compounds or drugs for cancer treatment. Many cytotoxic compounds, however, show undesirable toxicity at higher concentrations. Such undesirable activity may be reduced or eliminated by using lower doses of the cytotoxic compound in combination with another compound that modulates its activity. Here, we have examined the cytotoxicity of four microbial metabolites [ethyl N-(2-phenethyl) carbamate (NP-1), Euglenophycin, Anabaenopeptin, and Glycolipid 652] using three in vitro cell lines [human breast cancer cells (MCF-7), mouse neuroblastoma cells (N2a), and rat pituitary epithelial cells (GH4C1)]. The compounds showed variable cytotoxicity, with Euglenophycin displaying specificity for N2a cells. We have also examined the modulatory power of NP-1 on the cytotoxicity of the other three compounds and found that at a permissible concentration (125 µg/mL), NP-1 sensitized N2a and MCF-7 cells to Euglenophycin and Glycolipid 652 induced cytotoxicity.
authors.affiliation: Biosortia Pharmaceuticals, 565 Metro Place South, Suite 300, Dublin, OH 43017, USA. pwahome@biosortia.com.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Wahome
authors.affiliation: Biosortia Pharmaceuticals, 565 Metro Place South, Suite 300, Dublin, OH 43017, USA. kbeauchesne@biosortia.com.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Beauchesne
authors.affiliation: Biosortia Pharmaceuticals, 565 Metro Place South, Suite 300, Dublin, OH 43017, USA. apedone@biosortia.com.
authors.forename: Anna C
authors.initials: AC
authors.lastname: Pedone
authors.affiliation: Department of Molecular & Structural Biochemistry, North Carolina State University, Campus Box 7622, 128 Polk Hall, Raleigh, NC 27695, USA. john_cavanagh@ncsu.edu.
authors.forename: John
authors.initials: J
authors.lastname: Cavanagh
authors.affiliation: Department Chemistry, North Carolina State University, 2620 Yarbrough Drive, Box 8204, Raleigh, North Carolina 27695, USA. christian_melander@ncsu.edu.
authors.forename: Christian
authors.initials: C
authors.lastname: Melander
authors.affiliation: Department of Life Sciences, Texas A&M Corpus Christi, 6300 Ocean Drive, Corpus Christi, TX 78412, USA. paul.zimba@tamucc.edu.
authors.forename: Paul
authors.initials: P
authors.lastname: Zimba
authors.affiliation: Toxin/Natural Products Chemistry, National Ocean Service/NOAA, Hollings Marine Lab, 331 Fort Johnson Road, Charleston, SC 29412, USA. peter.moeller@noaa.gov.
authors.forename: Peter D R
authors.initials: PD
authors.lastname: Moeller
mesh_terms: D000277:Adjuvants, Pharmaceutic / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001688:Biological Products / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor / Q000187:drug effects; D006017:Glycolipids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D061986:MCF-7 Cells / Q000187:drug effects; D008387:Marine Toxins / Q000008:administration & dosage / Q000627:therapeutic use; D051379:Mice; D009447:Neuroblastoma / Q000188:drug therapy; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000627:therapeutic use; D010880:Piperidines / Q000008:administration & dosage / Q000627:therapeutic use; D051381:Rats; D012623:Seawater / Q000382:microbiology; D013844:Thiazoles / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D000277:Adjuvants, Pharmaceutic; D000970:Antineoplastic Agents; D001688:Biological Products; D006017:Glycolipids; D008387:Marine Toxins; C572148:NP-1 compound; D010456:Peptides, Cyclic; D010880:Piperidines; D013844:Thiazoles; C496665:anabaenopeptin B; C547753:euglenophycin