title: Binding partners for curcumin in human schwannoma cells: biologic implications.
abstract: Curcumin (diferuloylmethane) is a potent anti-inflammatory and anti-tumorigenic agent that has shown preclinical activity in diverse cancers. Curcumin up-regulates heat shock protein 70 (hsp70) mRNA in several different cancer cell lines. Hsp70 contributes to an escape from the apoptotic effects of curcumin by several different mechanisms including prevention of the release of apoptosis inducing factor from the mitochondria and inhibition of caspases 3 and 9. Previously we showed that the combination of curcumin plus a heat shock protein inhibitor was synergistic in its down-regulation of the proliferation of a human schwannoma cell line (HEI-193) harboring an NF2 mutation, possibly because curcumin up-regulated hsp70, which also binds merlin, the NF2 gene product. In order to determine if curcumin also interacts directly with hsp70 and to discover other binding partners of curcumin, we synthesized biotinylated curcumin (bio-curcumin) and treated HEI-193 schwannoma cells. Cell lysates were prepared and incubated with avidin-coated beads. Peptides pulled down from this reaction were sequenced and it was determined that biotinylated curcumin bound hsp70, hsp90, 3-phosphoglycerate dehydrogenase, and a β-actin variant. These binding partners may serve to further elucidate the underlying mechanisms of curcumin's actions.
authors.affiliation: Department of Investigational Cancer Therapeutics, (Phase I Program), The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. lsangelo39@gmail.com
authors.forename: Laura S
authors.initials: LS
authors.lastname: Angelo
authors.forename: David S
authors.initials: DS
authors.lastname: Maxwell
authors.forename: Ji Yuan
authors.initials: JY
authors.lastname: Wu
authors.forename: Duoli
authors.initials: D
authors.lastname: Sun
authors.forename: David H
authors.initials: DH
authors.lastname: Hawke
authors.forename: Ian E
authors.initials: IE
authors.lastname: McCutcheon
authors.forename: John M
authors.initials: JM
authors.lastname: Slopis
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Peng
authors.forename: William G
authors.initials: WG
authors.lastname: Bornmann
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
mesh_terms: D001665:Binding Sites; D001710:Biotin / Q000737:chemistry; D045744:Cell Line, Tumor; D003474:Curcumin / Q000737:chemistry* / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry* / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D062105:Molecular Docking Simulation; D009442:Neurilemmoma / Q000378:metabolism / Q000473:pathology; D050543:Phosphoglycerate Dehydrogenase / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D001710:Biotin; D050543:Phosphoglycerate Dehydrogenase; D003474:Curcumin