title: Platinum (IV) coiled coil nanotubes selectively kill human glioblastoma cells.
abstract: Malignant glioma are often fatal and pose a significant therapeutic challenge. Here we have employed α-helical right handed coiled coils (RHCC) which self-assemble into tetrameric nanotubes that stably associate with platinum (Pt) (IV) compound. This Pt(IV)-RHCC complex showed superior in vitro and in vivo toxicity in human malignant glioma cells at up to 5 fold lower platinum concentrations when compared to free Pt(IV). Pt(IV)-RHCC nanotubes activated multiple cell death pathways in GB cells without affecting astrocytes in vitro or causing damage to normal mouse brain. This Pt(IV)-RHCC nanotubes may serve as a promising new therapeutic tool for low dose Pt(IV) prodrug application for highly efficient and selective treatment of human brain tumors.
  
  
  BACKGROUND
  The prognosis of malignant glioma remains poor despite medical advances. Platinum, one of the chemotherapeutic agents used, has significant systemic side effects. In this article, the authors employed α-helical right handed coiled coil (RHCC) protein nanotubes as a carrier for cisplatin. It was shown that the new compound achieved higher tumor kill rate but lower toxicity to normal cells and thus may hold promise to be a highly efficient treatment for the future.
authors: Dept. of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, MB, Canada.
authors: Thatchawan
authors: T
authors: Thanasupawat
authors: Dept. of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, MB, Canada.
authors: Hugo
authors: H
authors: Bergen
authors: Dept. of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, MB, Canada; Dept. of Obstetrics, Gynecology and Reproductive Medicine, University of Manitoba, Winnipeg, MB, Canada.
authors: Sabine
authors: S
authors: Hombach-Klonisch
authors: Dept. of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, MB, Canada; Dept. of Surgery, University of Manitoba, Winnipeg, MB, Canada.
authors: Jerry
authors: J
authors: Krcek
authors: Dept. of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, MB, Canada.
authors: Saeid
authors: S
authors: Ghavami
authors: Dept. of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, MB, Canada; Dept. of Pathology, University of Manitoba, Winnipeg, MB, Canada.
authors: Marc R
authors: MR
authors: Del Bigio
authors: Dept. of Pathology, University of Manitoba, Winnipeg, MB, Canada.
authors: Sherry
authors: S
authors: Krawitz
authors: Dept. of Physiology, University of Manitoba, Winnipeg, MB, Canada.
authors: Gerald
authors: G
authors: Stelmack
authors: Dept. of Physiology, University of Manitoba, Winnipeg, MB, Canada.
authors: Andrew
authors: A
authors: Halayko
authors: Dept. of Chemistry, University of Manitoba, Winnipeg, MB, Canada.
authors: Matthew
authors: M
authors: McDougall
authors: Dept. of Chemistry, University of Manitoba, Winnipeg, MB, Canada.
authors: Markus
authors: M
authors: Meier
authors: Dept. of Chemistry, University of Manitoba, Winnipeg, MB, Canada; Dept. of Biochemistry and Medical Genetics, Winnipeg, MB, Canada.
authors: Jörg
authors: J
authors: Stetefeld
authors: Dept. of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, MB, Canada; Dept. of Surgery, University of Manitoba, Winnipeg, MB, Canada; Dept. of Medical Microbiology & Infectious Diseases, Winnipeg, MB, Canada; Dept. of Human Anatomy and Cell Science, Faculty of Health Sciences, College of Medicine, University of Manitoba, Winnipeg, MB, Canada. Electronic address: thomas.klonisch@med.umanitoba.ca.
authors: Thomas
authors: T
authors: Klonisch
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051379:Mice; D043942:Nanotubes / Q000737:chemistry*; D017671:Platinum Compounds / Q000737:chemistry / Q000494:pharmacology*; D011355:Prodrugs / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D017671:Platinum Compounds; D011355:Prodrugs
keywords: Glioblastoma; Nanotubes; Platinum; Prodrug; RHCC; Right handed coiled coil