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Pregled bibliografske jedinice broj: 505157

In vivo toxicity study of N-1-sulfonylcytosine derivatives and their mechanisms of action in cervical carcinoma cell line


Kašnar-Šamprec, Jelena; Ratkaj, Ivana; Mišković, Katarina; Pavlak, Marina; Baus-Lončar, Mirela; Kraljević Pavelić, Sandra; Glavaš-Obrovac, Ljubica; Žinić, Biserka
In vivo toxicity study of N-1-sulfonylcytosine derivatives and their mechanisms of action in cervical carcinoma cell line // Investigational new drugs, 30 (2012), 3; 981-990 doi:10.1007/s10637-011-9657-x (međunarodna recenzija, članak, znanstveni)


Naslov
In vivo toxicity study of N-1-sulfonylcytosine derivatives and their mechanisms of action in cervical carcinoma cell line

Autori
Kašnar-Šamprec, Jelena ; Ratkaj, Ivana ; Mišković, Katarina ; Pavlak, Marina ; Baus-Lončar, Mirela ; Kraljević Pavelić, Sandra ; Glavaš-Obrovac, Ljubica ; Žinić, Biserka

Izvornik
Investigational new drugs (0167-6997) 30 (2012), 3; 981-990

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
N-1-sulfonylcytosine derivatives; antitumour agents; in vitro screening; in vivo screening

Sažetak
New N-1-sulfonylpyrimidines showed potent growth inhibitory activity against human and mouse tumour cells of different origin. 1-(p-toluenesulfonyl)cytosine (TsC) and 1-(p-toluenesulfonyl)cytosine hydrochloride (TsC×HCl) inhibited the growth of human cervical carcinoma cells (HeLa), and had no significant cytotoxic effects on normal human foreskin fibroblasts (BJ). TsC and TsC×HCl interfered with the HeLa cell cycle progression bringing about the accumulation of G1 phase cells and the induction of apoptosis. Antiproliferative effects of TsC and TsC×HCl were additionally confirmed by investigating de novo synthesis of RNA, DNA and proteins in HeLa cells. Monitoring gene expression using DNA Chip Analysis and quantitative PCR showed that TsC×HCl affects the expression of several cell-cycle regulating genes implying that cell cycle arrest and DNA damage-induced apoptosis might account for the observed cellular effects. In vivo experiments revealed low toxicity of TsC×HCl, as demonstrated by unaltered haematological and metabolic blood parameters. In conclusion, potent antitumour efficacy and low toxicity of new compounds in comparison with the common chemotherapy drug 5-FU make them promising anticancer agents. Additional pre-clinical and clinical studies are warranted to illuminate the mode of action of these newly synthesized compounds in vivo, which would lay the groundwork for their further optimization.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija, Temeljne medicinske znanosti



POVEZANOST RADA


Projekt / tema
098-0982914-2935 - Sinteza novih biološki aktivnih derivata nukleobaza i nukleotida (Biserka Žinić, )
219-0982914-2176 - Mehanizam bioloških učinaka novih malih molekula na stanice tumora čovjeka (Ljubica Glavaš Obrovac, )
219-0982914-2179 - Uloga malih zaštitinih TFF proteina u zdravlju i bolesti (Tatjana Belovari, )
335-0000000-3532 - Uloga IGF2 i signalni putovi nizvodno u karcinomima pluća čovjeka (Sandra Kraljević Pavelić, )
335-0982464-2393 - Molekularna obilježja miofibroblasta Dupuytrenove bolesti (Krešimir Pavelić, )

Ustanove
Veterinarski fakultet, Zagreb,
Institut "Ruđer Bošković", Zagreb,
Klinički bolnički centar Osijek,
Medicinski fakultet, Osijek,
Sveučilište u Rijeci - Odjel za biotehnologiju

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


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