title: The ability of hyaluronan fragments to reverse the resistance of C6 rat glioma cell line to temozolomide and carmustine.
abstract: OBJECTIVE
  Hyaluronan (HA) is an extracellular matrix (ECM) polymer that may contribute to the emergence of anti-cancer drug resistance. Attempts to reverse drug resistance using small hyaluronan oligomers (oHA) are being made. The initial reports suggest that the oHA fraction may effectively reverse anti-cancer drug resistance in glioma models. However, the reversal effects of oHA of defined molecular length on glioma cells have not been investigated yet. In this study, we examined HA fragments containing 2 disaccharide units (oHA-2), 5 disaccharide units (oHA-5), and 68 kDa hyaluronan polymer (HA-68k) as agents possibly reversing the resistance of a C6 rat glioma cell line to temozolomide (TMZ) and carmustine (BCNU).
  
  
  METHODS
  A 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) viability assay was used to assess the cytotoxicity of TMZ and BCNU in the presence or absence of the hyaluronan fragments. By comparing viability of the cells, the reversal effects of HA fragments on TMZ and BCNU resistance in C6 glioma cells were assessed.
  
  
  RESULTS
  We found statistically significant decreases in the viability of cells in the presence of TMZ+oHA-5 as compared to TMZ alone (51.2 ±4.5 vs. 74.2 ±5.8, p = 0.0031), BCNU+o-HA5 as compared to BCNU alone (49.3 ±4.4 vs. 65.6 ±5.7, p = 0.0119), and BCNU+HA-68k as compared to BCNU alone (55.2 ±2.3 vs. 65.6 ±5.7, p = 0.0496).
  
  
  CONCLUSIONS
  
  
  
  CONCLUSIONS
  Hyaluronan oligomers of 5 disaccharide units (oHA-5) significantly reversed the resistance of C6 cells to TMZ and BCNU. The results are only preliminary and a more thorough follow-up investigation is required to assess their actual role.
authors.affiliation: Department of Pharmacology and Toxicology, Medical University of Lodz, Lodz, Poland.
authors.forename: Michał Seweryn
authors.initials: MS
authors.lastname: Karbownik
authors.affiliation: Department of Pneumology and Allergology, Medical University of Lodz, Lodz, Poland.
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Pietras
authors.affiliation: Department of Medical Biochemistry, Medical University of Lodz, Lodz, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Szemraj
authors.affiliation: Department of Pharmacology and Toxicology, Medical University of Lodz, Lodz, Poland.
authors.forename: Edward
authors.initials: E
authors.lastname: Kowalczyk
authors.affiliation: Department of Pharmacology and Toxicology, Medical University of Lodz, Lodz, Poland ; Institute of Pharmacology, Polish Academy of Sciences, Scientific Board, Krakow, Poland, and Medical Center MEDYCEUSZ in Lodz, Poland.
authors.forename: Jerzy Zygmunt
authors.initials: JZ
authors.lastname: Nowak
keywords: CD44; carmustine; drug resistance; glioma; hyaluronan oligomers; temozolomide