title: In vivo anticancer activity of rhomboidal Pt(II) metallacycles.
abstract: The development of novel antitumor agents that have high efficacy in suppressing tumor growth, have low toxicity to nontumor tissues, and exhibit rapid localization in the targeted tumor sites is an ongoing avenue of research at the interface of chemistry, cancer biology, and pharmacology. Supramolecular metal-based coordination complexes (SCCs) have well-defined shapes and geometries, and upon their internalization, SCCs could affect multiple oncogenic signaling pathways in cells and tissues. We investigated the uptake, intracellular localization, and antitumor activity of two rhomboidal Pt(II)-based SCCs. Laser-scanning confocal microscopy in A549 and HeLa cells was used to determine the uptake and localization of the assemblies within cells and their effect on tumor growth was investigated in mouse s.c. tumor xenograft models. The SCCs are soluble in cell culture media within the entire range of studied concentrations (1 nM-5 µM), are nontoxic, and showed efficacy in reducing the rate of tumor growth in s.c. mouse tumor xenografts. These properties reveal the potential of Pt(II)-based SCCs for future biomedical applications as therapeutic agents.
authors.affiliation: School of Pharmacy, University of Southern California, Los Angeles, CA 90089; and.
authors.forename: Ivan V
authors.initials: IV
authors.lastname: Grishagin
authors.affiliation: Department of Chemistry, University of Utah, Salt Lake City, UT 84112.
authors.forename: J Bryant
authors.initials: JB
authors.lastname: Pollock
authors.affiliation: School of Pharmacy, University of Southern California, Los Angeles, CA 90089; and.
authors.forename: Swati
authors.initials: S
authors.lastname: Kushal
authors.affiliation: Department of Chemistry, University of Utah, Salt Lake City, UT 84112.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Cook
authors.affiliation: Department of Chemistry, University of Utah, Salt Lake City, UT 84112 stang@chem.utah.edu bogdan@usc.edu.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Stang
authors.affiliation: School of Pharmacy, University of Southern California, Los Angeles, CA 90089; and stang@chem.utah.edu bogdan@usc.edu.
authors.forename: Bogdan Z
authors.initials: BZ
authors.lastname: Olenyuk
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology; D010984:Platinum / Q000737:chemistry / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D010984:Platinum
keywords: cell culture; fluorescence; supramolecular coordination complexes; tumor growth; xenografts