Novi kompleksi zlata pincer-tipa indukuju kaspaza-zavisnu apoptozu u humanim ćelijama raka in vitro

  • Milan M. Zarić University of Kragujevac, Faculty of Medical Sciences, Department of Biochemistry, Kragujevac, Serbia
  • Petar P. Čanović University of Kragujevac, Faculty of Medical Sciences, Department of Biochemistry, Kragujevac, Serbia
  • Marijana Stanojević Pirković University of Kragujevac, Faculty of Medical Sciences, Department of Biochemistry, Kragujevac, Serbia
  • Sanja M. Knežević University of Kragujevac, Faculty of Medical Sciences, Department of Pediatrics, Kragujevac, Serbia
  • Radica S. Živković Zarić University of Kragujevac, Faculty of Medical Sciences, Department of Pharmacology and Toxicology, Kragujevac, Serbia
  • Biljana Popovska Jovičić University of Kragujevac, Faculty of Medical Sciences, Department of Infectious Diseases, Kragujevac, Serbia
  • Nedim Hamzagić Medical Center Tutin, Center of Hemodialysis, Tutin, Serbia
  • Bojana Simović Marković University of Kragujevac, Faculty of Medical Sciences, Center for Molecular Medicine and Stem Cell Research, Kragujevac, Serbia
  • Nenad Marković University of Kragujevac, Faculty of Medical Sciences, Department of Surgery, Kragujevac, Serbia
  • Ana Rilak Simović University of Kragujevac, Faculty of Medical Sciences, Department of Chemistry, Kragujevac, Serbia
DOI: https://doi.org/10.2298/VSP190507002Z
Ključne reči: antineoplastici, apoptoza, kaspaze, testovi, enzimski, zlato, jedinjenja, neoplazme, toksičnost, testovi

Sažetak


Uvod/Cilj. Upotreba cisplatine kao citostatika je otvorila vrata za istraživanje novih lekova koji u svojoj strukturi sadrže neki od metala. Novi kompleksi koji sadrže metale poput platine, paladijuma, rutenijuma i zlata se od nedavno ispituju kao potencijalni antitumorski lekovi. Cilj rada bio je da se ispita citotoksičnost Au(III) kompleksa sa ligandima tipa pincer protiv ćelija karcinoma grlića materice (HeLa), ćelija raka dojke (MDA-MB-231 i 4T1) i ćelija karcinoma kolona (HCT116 i CT26), kao i tip i mehanizam ćelijske smrti koji ti kompleksi indukuju u ćelijama raka. Metode. Citotoksičnost Au(III) kompleksa je ispitivana pomoću MTT testa. Apoptoza tretiranih ćelija raka je merena protočnom citometrijom i primenom bojenja Aneksin V/7AAD. Ekspresija aktivnog proapoptotičnog proteina Bax, antiapoptotskog proteina Bcl-2 i procenat ćelija koje sadrže aktivnu kaspazu-3 u tretiranim ćelijama raka određena je protočnom citometrijom. Rezultati. Kompleks 1 je pokazao najsnažniji antitumorski efekat na HeLa ćelije, kako u poređenju sa drugim ispitivanim kompleksima zlata, tako i u poređenju sa cisplatinom. Vrednosti IC50 kompleksa zlata na HeLa ćelije nakon 72 sata bile su 1,3 ± 0,4 μM, 3,4 ± 1,3 μM, 5,7 ± 0,6 μM, 26,7 ± 6,5 μM za komplekse 1, 2, 3 i cisplatin, redom. Kompleks 1 je takođe pokazao najvišu citotoksičnost prema MDA-MB-231 i HCT116 ćelijama u poređenju sa drugim testiranim jedinjenjima. Rezultati bojenja aneksinomV/7AAD pokazali su da sva tri kompleksa zlata indukuju apoptozu u tretiranim ćelijama. Naši kompleksi Au(III) indukovali su apoptozu mehanizmom koji je zavisio od kaspaze, ali nismo pokazali da je u tretiranim ćelijama raka došlo do aktivacije unutrašnjeg puta apoptoze. Zaključak. Prema rezultatima naše in vitro studije, sva tri jedinjenja zlata, a posebno kompleks 1, obećavajući su kandidati za novu generaciju antikancerogenih lekova.

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Objavljeno
2021/08/24
Broj časopisa
Vol. 78 Br. 8 (2021): Vojnosanitetski pregled
Rubrika
Originalni članak