Investigation of the antitumor effect of enones and their salts on human malignant cells in vitro

[M. S. Bulić]

111 listova

Uvod: Lečenje tumora je udruženo sa problemom ograničene efikasnosti trenutnih terapijskih protokola. Veliki broj istraživanja usmeren je na sintezu jedinjenja sa antitumorskim dejstvom, a značajan broj njih potiče od hemijskih derivata prirodnih supstanci ili njihovih modifikovanih analoga. Cilj: Glavni cilj ovog istraživanja je in vitro ispitivanje antitumorskog dejstva novosintetisanih enona i njihovih soli. Metod: Istraživanjem je ispitan antitumorski efekat osam novosintetisanih supstanci - četiri enona i njihovih soli na humanim ćelijskim linijama karcinoma debelog creva i grlića materice, kao i na zdravim ćelijama. Takođe je ispitan efekat ovih supstanci na kontrolnu grupu zdravih ćelija. Metodologija istraživanja obuhvatila je ispitivanje citotoksičnog efekta korišćenjem MTT testa, protočnu citometriju za analizu ćelijskog ciklusa i apoptoze, kao i imunofluorescentne tehnike ispitivanja molekularnih mehanizama koji indukuju ćelijsku smrt. Rezultati: Novosintetisani enoni i njihove soli ispoljavaju jači citotoksični efekat na ćelijama karcinoma debelog creva i karcinoma grlića materice in vitro u poređenju sa referentnom supstancom - cisplatinom. Ovi rezultati takođe daju važne informacije o selektivnosti ovih lekova prema malignim ćelijama u odnosu na zdrave ćelije, što je od suštinskog značaja za razvoj efikasnijih i bezbednijih terapeutika. Mehanizmi koji stoje u osnovi citotoksičnog dejstva novosintetisanih enona i njihovih soli uključuju indukciju apoptoze i njihov uticaj na zaustavljanje ćelijskog ciklusa. Zaključak: Novosintetisani enoni i njihove soli pokazuju značajan citotoksični efekat na maligne ćelije in vitro i neznatan citotoksični efekat prema zdravim ćelijama što ukazuje na njihov potencijal za in vivo istraživanja.

Introduction: Tumor treatment is associated with with limited efficacy of current therapeutic protocols. A large number of studies is focused on the synthesis of antitumor compounds originating from natural substances or their modified analogues. Objective: The main objective of this research is to investigate the in vitro antitumor activity of newly synthesized enones and their salts. Method: The research examined the antitumor effect of eight newly synthesized substances - four enones and their salts - on human colon and cervical cancer and healthy cell lines. The effect of these substances on a control group of healthy cells was also examined. The research methodology included determination of cytotoxic effect of investigated substances using the MTT assay, flow cytometry for cell cycle and apoptosis analysis, as well as immunofluorescence techniques for testing molecular mechanisms that. Results: Newly synthesized enones and their salts exhibit a stronger cytotoxic effect on colon and cervical cancer cells in vitro compared to referent substance - cisplatin. These results also provide important information about the selectivity of these drugs towards malignant cells over healthy cells, which is essential for the development of more effective and safer therapeutics. The mechanisms underlying the cytotoxic effects of the newly synthesized enones and their salts include the induction of apoptosis and cell cycle arrest. Conclusion: The newly synthesized enones and their salts show a significant cytotoxic effect on malignant cells in vitro and a slight cytotoxic effect on healthy cells, indicating their potential for in vivo research.

enoni, soli enona, karcinom, citotoksičnost, apoptoza, ćelijski ciklus.

enones, enone salts, cancer, cytotoxicity, apoptosis, cell cycle.

577.1:616‑006.6-08-092.4(043.3)

Medicinska biohemija

Tekst