Selenotriapine - An isostere of the most studied thiosemicarbazone with pronounced pro-apoptotic activity, low toxicity and ability to challenge phenotype reprogramming of 3-D mammary adenocarcinoma tumors
Autori
Filipović, Nenad R.Bjelogrlić, Snežana K.
Pelliccia, Sveva
Jovanović, Vesna B.
Kojić, Milan
Sencanski, Milan
La Regina, Giuseppe
Silvestri, Romano
Muller, Christian D.
Todorović, Tamara R.
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
Triapine, the most studied alpha-N-heterocyclic thiosemicarbazone, revealed potent activity against advanced leukemia, but was ineffective against a variety of solid tumors. Moreover, methemoglobinemia, which is a side effect of triapine administration, may limits all clinical application. To enhance anticancer activity and reduce side effects, we applied an isosteric replacement of sulfur to selenium atom was performed by synthesis and characterization of selenium triapine analog, 3-aminopyridine-2-carboxaldehyde selenosemicarbazone (selenotriapine). Compared to triapine, selenotriapine revealed superior pro-apoptotic activity with activation of intrinsic apoptotic pathway in both human monocytic leukemia (THP-1) and mammary adenocarcinoma (MCF-7) cell lines. For MCF-7 2-D cultures, selenotriapine induced notable increase in mitochondrial superoxide radical generation and dissipation of mitochondrial transmembrane potential. A significant delay in growth of MCF-7 spheroids (3-D cultur...e) was accompanied by phenotypic stem cell reprogramming (Oct-4 expression). Additionally, selenotriapine demonstrated a very low toxicity profile as compared to triapine, confirmed over alleviated extent of methemoglobin formation and higher IC50 value in brine shrimp cytotoxicity assay.
Ključne reči:
Selenosemicarbazone / Oct-4 / Mitochondrial superoxide production / Apoptosis / 3-D cultureIzvor:
Arabian Journal of Chemistry, 2020, 13, 1, 1466-1489Izdavač:
- Elsevier, Amsterdam
Finansiranje / projekti:
- COST [CA15135, CA16119]
- PRIN 2015 [2015FCHJ8E]
- Interakcije prirodnih proizvoda, njihovih derivata i kompleksnih jedinjenja sa proteinima i nukleinskim kiselinama (RS-MESTD-Basic Research (BR or ON)-172055)
DOI: 10.1016/j.arabjc.2017.11.017
ISSN: 1878-5352
WoS: 000505076000109
Scopus: 2-s2.0-85037552505
Institucija/grupa
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Filipović, Nenad R. AU - Bjelogrlić, Snežana K. AU - Pelliccia, Sveva AU - Jovanović, Vesna B. AU - Kojić, Milan AU - Sencanski, Milan AU - La Regina, Giuseppe AU - Silvestri, Romano AU - Muller, Christian D. AU - Todorović, Tamara R. PY - 2020 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1407 AB - Triapine, the most studied alpha-N-heterocyclic thiosemicarbazone, revealed potent activity against advanced leukemia, but was ineffective against a variety of solid tumors. Moreover, methemoglobinemia, which is a side effect of triapine administration, may limits all clinical application. To enhance anticancer activity and reduce side effects, we applied an isosteric replacement of sulfur to selenium atom was performed by synthesis and characterization of selenium triapine analog, 3-aminopyridine-2-carboxaldehyde selenosemicarbazone (selenotriapine). Compared to triapine, selenotriapine revealed superior pro-apoptotic activity with activation of intrinsic apoptotic pathway in both human monocytic leukemia (THP-1) and mammary adenocarcinoma (MCF-7) cell lines. For MCF-7 2-D cultures, selenotriapine induced notable increase in mitochondrial superoxide radical generation and dissipation of mitochondrial transmembrane potential. A significant delay in growth of MCF-7 spheroids (3-D culture) was accompanied by phenotypic stem cell reprogramming (Oct-4 expression). Additionally, selenotriapine demonstrated a very low toxicity profile as compared to triapine, confirmed over alleviated extent of methemoglobin formation and higher IC50 value in brine shrimp cytotoxicity assay. PB - Elsevier, Amsterdam T2 - Arabian Journal of Chemistry T1 - Selenotriapine - An isostere of the most studied thiosemicarbazone with pronounced pro-apoptotic activity, low toxicity and ability to challenge phenotype reprogramming of 3-D mammary adenocarcinoma tumors EP - 1489 IS - 1 SP - 1466 VL - 13 DO - 10.1016/j.arabjc.2017.11.017 ER -
@article{ author = "Filipović, Nenad R. and Bjelogrlić, Snežana K. and Pelliccia, Sveva and Jovanović, Vesna B. and Kojić, Milan and Sencanski, Milan and La Regina, Giuseppe and Silvestri, Romano and Muller, Christian D. and Todorović, Tamara R.", year = "2020", abstract = "Triapine, the most studied alpha-N-heterocyclic thiosemicarbazone, revealed potent activity against advanced leukemia, but was ineffective against a variety of solid tumors. Moreover, methemoglobinemia, which is a side effect of triapine administration, may limits all clinical application. To enhance anticancer activity and reduce side effects, we applied an isosteric replacement of sulfur to selenium atom was performed by synthesis and characterization of selenium triapine analog, 3-aminopyridine-2-carboxaldehyde selenosemicarbazone (selenotriapine). Compared to triapine, selenotriapine revealed superior pro-apoptotic activity with activation of intrinsic apoptotic pathway in both human monocytic leukemia (THP-1) and mammary adenocarcinoma (MCF-7) cell lines. For MCF-7 2-D cultures, selenotriapine induced notable increase in mitochondrial superoxide radical generation and dissipation of mitochondrial transmembrane potential. A significant delay in growth of MCF-7 spheroids (3-D culture) was accompanied by phenotypic stem cell reprogramming (Oct-4 expression). Additionally, selenotriapine demonstrated a very low toxicity profile as compared to triapine, confirmed over alleviated extent of methemoglobin formation and higher IC50 value in brine shrimp cytotoxicity assay.", publisher = "Elsevier, Amsterdam", journal = "Arabian Journal of Chemistry", title = "Selenotriapine - An isostere of the most studied thiosemicarbazone with pronounced pro-apoptotic activity, low toxicity and ability to challenge phenotype reprogramming of 3-D mammary adenocarcinoma tumors", pages = "1489-1466", number = "1", volume = "13", doi = "10.1016/j.arabjc.2017.11.017" }
Filipović, N. R., Bjelogrlić, S. K., Pelliccia, S., Jovanović, V. B., Kojić, M., Sencanski, M., La Regina, G., Silvestri, R., Muller, C. D.,& Todorović, T. R.. (2020). Selenotriapine - An isostere of the most studied thiosemicarbazone with pronounced pro-apoptotic activity, low toxicity and ability to challenge phenotype reprogramming of 3-D mammary adenocarcinoma tumors. in Arabian Journal of Chemistry Elsevier, Amsterdam., 13(1), 1466-1489. https://doi.org/10.1016/j.arabjc.2017.11.017
Filipović NR, Bjelogrlić SK, Pelliccia S, Jovanović VB, Kojić M, Sencanski M, La Regina G, Silvestri R, Muller CD, Todorović TR. Selenotriapine - An isostere of the most studied thiosemicarbazone with pronounced pro-apoptotic activity, low toxicity and ability to challenge phenotype reprogramming of 3-D mammary adenocarcinoma tumors. in Arabian Journal of Chemistry. 2020;13(1):1466-1489. doi:10.1016/j.arabjc.2017.11.017 .
Filipović, Nenad R., Bjelogrlić, Snežana K., Pelliccia, Sveva, Jovanović, Vesna B., Kojić, Milan, Sencanski, Milan, La Regina, Giuseppe, Silvestri, Romano, Muller, Christian D., Todorović, Tamara R., "Selenotriapine - An isostere of the most studied thiosemicarbazone with pronounced pro-apoptotic activity, low toxicity and ability to challenge phenotype reprogramming of 3-D mammary adenocarcinoma tumors" in Arabian Journal of Chemistry, 13, no. 1 (2020):1466-1489, https://doi.org/10.1016/j.arabjc.2017.11.017 . .