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Pregled bibliografske jedinice broj: 487722

Putative mechanisms of antitumor activity of cyano-substituted heteroaryles in HeLa cells


Ester, Katja; Supek, Fran; Majsec, Kristina; Marjanović, Marko; Lembo, David; Donalisio, Manuela; Šmuc, Tomislav; Jarak, Ivana; Karminski-Zamola, Grace; Kralj, Marijeta
Putative mechanisms of antitumor activity of cyano-substituted heteroaryles in HeLa cells // Investigational new drugs, 30 (2012), 2; 450-467 doi:10.1007/s10637-010-9571-7 (međunarodna recenzija, članak, znanstveni)


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Naslov
Putative mechanisms of antitumor activity of cyano-substituted heteroaryles in HeLa cells

Autori
Ester, Katja ; Supek, Fran ; Majsec, Kristina ; Marjanović, Marko ; Lembo, David ; Donalisio, Manuela ; Šmuc, Tomislav ; Jarak, Ivana ; Karminski-Zamola, Grace ; Kralj, Marijeta

Izvornik
Investigational new drugs (0167-6997) 30 (2012), 2; 450-467

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

Ključne riječi
cyano-substituted heteroaryles; HeLa cells; Random forest; apoptosis; cytoskeleton disruption; antioxidants

Sažetak
Six recently synthesized cyano-substituted heteroaryles, which do not bind to DNA but are highly cytotoxic against the human tumor cell line HeLa, were analyzed for their antitumor mechanisms of action (MOA). They did not interfere with the expression of human papillomavirus oncogenes integrated in the HeLa cell genome, but they did induce strong G1 arrest and result in the activation of caspase-3 and apoptosis. A computational analysis was performed that compared the antiproliferative activities of our compounds in 13 different tumor cell lines with those of compounds listed in the National Cancer Institute database. The results indicate that interference with cytoskeletal function and inhibition of mitosis are the likely antitumor MOA. Furthermore, a second in silico investigation revealed that the tumor cells that are sensitive to the cyano-substituted compounds show differences in their expression of locomotion genes compared with that of insensitive cell lines, thus corroborating the involvement of the cytoskeleton. This MOA was also confirmed experimentally: the cyano-substituted heteroaryles disrupted the actin and the tubulin networks in HeLa cells and inhibited cellular migration. However, further analysis indicated that multiple MOA may exist that depend on the position of the cyano-group ; while cyano-substituted naphthiophene reduced the expression of cytoskeletal proteins, cyano-substituted thieno-thiophene-carboxanilide inhibited the formation of cellular reactive oxygen species.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija, Temeljne medicinske znanosti



POVEZANOST RADA


Projekt / tema
098-0000000-3168 - Strojno učenje prediktivnih modela u računalnoj biologiji (Tomislav Šmuc, )
098-0982464-2514 - Uloga različitih mehanizama odgovora stanica na terapiju oštećenjem DNA (Marijeta Kralj, )
125-0982464-1356 - Novi heterocikli kao antitumorski i antivirusni ("pametni") lijekovi (Marijana Hranjec, )

Ustanove
Institut "Ruđer Bošković", Zagreb,
Fakultet kemijskog inženjerstva i tehnologije, Zagreb

Citiraj ovu publikaciju

Ester, Katja; Supek, Fran; Majsec, Kristina; Marjanović, Marko; Lembo, David; Donalisio, Manuela; Šmuc, Tomislav; Jarak, Ivana; Karminski-Zamola, Grace; Kralj, Marijeta
Putative mechanisms of antitumor activity of cyano-substituted heteroaryles in HeLa cells // Investigational new drugs, 30 (2012), 2; 450-467 doi:10.1007/s10637-010-9571-7 (međunarodna recenzija, članak, znanstveni)
Ester, K., Supek, F., Majsec, K., Marjanović, M., Lembo, D., Donalisio, M., Šmuc, T., Jarak, I., Karminski-Zamola, G. & Kralj, M. (2012) Putative mechanisms of antitumor activity of cyano-substituted heteroaryles in HeLa cells. Investigational new drugs, 30 (2), 450-467 doi:10.1007/s10637-010-9571-7.
@article{article, year = {2012}, pages = {450-467}, DOI = {10.1007/s10637-010-9571-7}, keywords = {cyano-substituted heteroaryles, HeLa cells, Random forest, apoptosis, cytoskeleton disruption, antioxidants}, journal = {Investigational new drugs}, doi = {10.1007/s10637-010-9571-7}, volume = {30}, number = {2}, issn = {0167-6997}, title = {Putative mechanisms of antitumor activity of cyano-substituted heteroaryles in HeLa cells}, keyword = {cyano-substituted heteroaryles, HeLa cells, Random forest, apoptosis, cytoskeleton disruption, antioxidants} }

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


Uključenost u ostale bibliografske baze podataka:


  • Biological Sciences
  • BIOSIS Previews (Biological Abstracts)
  • CA Search (Chemical Abstracts)
  • EMBASE (Excerpta Medica)
  • IBSS - The International Bibliography of the Social Sciences
  • MEDLINE


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