To avoid the side effects of the anti-cancer drug doxorubicin (Dox), we conjugated this drug to a N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer backbone. Dox was conjugated via an amide bond (Dox-HPMA(AM), PK1) or a hydrazone pH-sensitive bond (Dox-HPMA(HYD)). In contrast to Dox and Dox-HPMA(HYD), Dox-HPMA(AM) accumulates within the cell's intracellular membranes, including those of the Golgi complex and endoplasmic reticulum, both involved in protein glycosylation. Flow cytometry was used to determine lectin binding and cell death, immunoblot to characterize the presence of CD7, CD43, CD44, and CD45, and high-performance anion exchange chromatography with pulsed amperometric detector analysis for characterization of plasma membrane saccharide composition. Incubation of EL4 cells with Dox-HPMA(AM) conjugate, in contrast to Dox or Dox-HPMA(HYD), increased the amounts of membrane surface-associated glycoproteins, as well as saccharide moieties recognized by peanut agglutinin, Erythrina cristagalli, or galectin-1 lectins. Only Dox-HPMA(AM) increased expression of the highly glycosylated membrane glycoprotein CD43, while expression of others (CD7, CD44, and CD45) was unaffected. The binding sites for galectin-1 are present on CD43 molecule. Furthermore, we present that EL4 treated with Dox-HPMA(AM) possesses increased sensitivity to galectin-1-induced apoptosis. In this study, we demonstrate that Dox-HPMA(AM) treatment changes glycosylation of the EL4 T cell lymphoma surface and sensitizes the cells to galectin-1-induced apoptosis.

• MeSH
• amidy chemie   MeSH
• antigeny CD43 metabolismus   MeSH
• apoptóza MeSH
• doxorubicin analogy a deriváty   farmakologie   MeSH
• endoplazmatické retikulum metabolismus   MeSH
• galektin 1 metabolismus   MeSH
• glykosylace MeSH
• Golgiho aparát metabolismus   MeSH
• kyseliny polymethakrylové farmakologie   MeSH
• lymfom T-buněčný farmakoterapie   metabolismus   patologie   MeSH
• myši MeSH
• nádorové buněčné linie účinky léků   MeSH
• nosiče léků MeSH
• proliferace buněk MeSH
• protinádorová antibiotika farmakologie   MeSH
• průtoková cytometrie MeSH
• western blotting MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• amidy MeSH
• antigeny CD43 MeSH
• doxorubicin-N-(2-hydroxypropyl)methacrylamide copolymer conjugate MeSH Prohlížeč
• doxorubicin MeSH
• galektin 1 MeSH
• kyseliny polymethakrylové MeSH
• nosiče léků MeSH
• protinádorová antibiotika MeSH