Biological evaluation of transdichloridoplatinum( II) complexes with 3-and 4-acetylpyridine in comparison to cisplatin
2013
Аутори
Filipović, LanaAranđelović, Sandra
Gligorijević, Nevenka
Krivokuca, Ana
Jankovic, Radmila
Srdić-Rajić, Tatjana
Rakic, Gordana
Tešić, Živoslav Lj.
Radulović, Siniša
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Background. In our previous study we reported the synthesis and cytotoxicity of two trans-platinum(II) complexes: trans-[PtCl2(3-acetylpyridine)(2)] (1) and trans-[PtCl2(4-acetylpyridine)(2)] (2), revealing significant cytotoxic potential of 2. In order to evaluate the mechanism underlying biological activity of both trans-Pt(II) isomers, comparative studies versus cisplatin were performed in HeLa, MRC-5 and MS1 cells. Materials and methods. The cytotoxic activity of the investigated complexes was determined using SRB assay. The colagenolytic activity was determined using gelatin zymography, while the effect of platinum complexes on matrix metalloproteinases 2 and 9 mRNA expression was evaluated by quantitative real-time PCR. Apoptotic potential and cell cycle alterations were determined by FACS analyses. Western blot analysis was used to evaluate the effect on expression of DNA-repair enzyme ERCC1, and quantitative real-time PCR was used for the ERCC1 mRNA expression analysis. In vitr...o antiangiogenic potential was determined by tube formation assay. Platinum content in intracellular DNA and proteins was determined by inductively coupled plasma-optical emission spectrometry. Results. Compound 2 displayed an apparent cytoselective profile, and flow cytometry analysis in HeLa cells indicated that 2 exerted antiproliferative effect through apoptosis induction, while 1 induced both apoptosis and necrosis. Action of 1 and 2, as analyzed by quantitative real-time PCR and Western blot, was associated with down-regulation of ERCC1. Both trans-complexes inhibited MMP-9 mRNA expression in HeLa, while 2 significantly abrogated in vitro tubulogenesis in MS1 cells. Conclusions. The ability of 2 to induce multiple and selective in vitro cytotoxic effects encourages further investigations of trans-platinum(II) complexes with substituted pyridines.
Кључне речи:
angiogenesis / apoptosis / MMPs / MRC-5 / trans-platinum(II)Извор:
Radiology and Oncology, 2013, 47, 4, 346-357Издавач:
- Assoc Radiology & Oncology, Ljubljana
Финансирање / пројекти:
- Фармакодинамска и фармакогеномска испитивања новијих лекова у лечењу солидних тумора (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41026)
- Корелација структуре и особина природних и синтетичких молекула и њихових комплекса са металима (RS-MESTD-Basic Research (BR or ON)-172017)
DOI: 10.2478/raon-2013-0050
ISSN: 1318-2099
PubMed: 24294179
WoS: 000325718800005
Scopus: 2-s2.0-84893721152
Колекције
Институција/група
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Filipović, Lana AU - Aranđelović, Sandra AU - Gligorijević, Nevenka AU - Krivokuca, Ana AU - Jankovic, Radmila AU - Srdić-Rajić, Tatjana AU - Rakic, Gordana AU - Tešić, Živoslav Lj. AU - Radulović, Siniša PY - 2013 UR - https://cherry.chem.bg.ac.rs/handle/123456789/1414 AB - Background. In our previous study we reported the synthesis and cytotoxicity of two trans-platinum(II) complexes: trans-[PtCl2(3-acetylpyridine)(2)] (1) and trans-[PtCl2(4-acetylpyridine)(2)] (2), revealing significant cytotoxic potential of 2. In order to evaluate the mechanism underlying biological activity of both trans-Pt(II) isomers, comparative studies versus cisplatin were performed in HeLa, MRC-5 and MS1 cells. Materials and methods. The cytotoxic activity of the investigated complexes was determined using SRB assay. The colagenolytic activity was determined using gelatin zymography, while the effect of platinum complexes on matrix metalloproteinases 2 and 9 mRNA expression was evaluated by quantitative real-time PCR. Apoptotic potential and cell cycle alterations were determined by FACS analyses. Western blot analysis was used to evaluate the effect on expression of DNA-repair enzyme ERCC1, and quantitative real-time PCR was used for the ERCC1 mRNA expression analysis. In vitro antiangiogenic potential was determined by tube formation assay. Platinum content in intracellular DNA and proteins was determined by inductively coupled plasma-optical emission spectrometry. Results. Compound 2 displayed an apparent cytoselective profile, and flow cytometry analysis in HeLa cells indicated that 2 exerted antiproliferative effect through apoptosis induction, while 1 induced both apoptosis and necrosis. Action of 1 and 2, as analyzed by quantitative real-time PCR and Western blot, was associated with down-regulation of ERCC1. Both trans-complexes inhibited MMP-9 mRNA expression in HeLa, while 2 significantly abrogated in vitro tubulogenesis in MS1 cells. Conclusions. The ability of 2 to induce multiple and selective in vitro cytotoxic effects encourages further investigations of trans-platinum(II) complexes with substituted pyridines. PB - Assoc Radiology & Oncology, Ljubljana T2 - Radiology and Oncology T1 - Biological evaluation of transdichloridoplatinum( II) complexes with 3-and 4-acetylpyridine in comparison to cisplatin VL - 47 IS - 4 SP - 346 EP - 357 DO - 10.2478/raon-2013-0050 ER -
@article{ author = "Filipović, Lana and Aranđelović, Sandra and Gligorijević, Nevenka and Krivokuca, Ana and Jankovic, Radmila and Srdić-Rajić, Tatjana and Rakic, Gordana and Tešić, Živoslav Lj. and Radulović, Siniša", year = "2013", abstract = "Background. In our previous study we reported the synthesis and cytotoxicity of two trans-platinum(II) complexes: trans-[PtCl2(3-acetylpyridine)(2)] (1) and trans-[PtCl2(4-acetylpyridine)(2)] (2), revealing significant cytotoxic potential of 2. In order to evaluate the mechanism underlying biological activity of both trans-Pt(II) isomers, comparative studies versus cisplatin were performed in HeLa, MRC-5 and MS1 cells. Materials and methods. The cytotoxic activity of the investigated complexes was determined using SRB assay. The colagenolytic activity was determined using gelatin zymography, while the effect of platinum complexes on matrix metalloproteinases 2 and 9 mRNA expression was evaluated by quantitative real-time PCR. Apoptotic potential and cell cycle alterations were determined by FACS analyses. Western blot analysis was used to evaluate the effect on expression of DNA-repair enzyme ERCC1, and quantitative real-time PCR was used for the ERCC1 mRNA expression analysis. In vitro antiangiogenic potential was determined by tube formation assay. Platinum content in intracellular DNA and proteins was determined by inductively coupled plasma-optical emission spectrometry. Results. Compound 2 displayed an apparent cytoselective profile, and flow cytometry analysis in HeLa cells indicated that 2 exerted antiproliferative effect through apoptosis induction, while 1 induced both apoptosis and necrosis. Action of 1 and 2, as analyzed by quantitative real-time PCR and Western blot, was associated with down-regulation of ERCC1. Both trans-complexes inhibited MMP-9 mRNA expression in HeLa, while 2 significantly abrogated in vitro tubulogenesis in MS1 cells. Conclusions. The ability of 2 to induce multiple and selective in vitro cytotoxic effects encourages further investigations of trans-platinum(II) complexes with substituted pyridines.", publisher = "Assoc Radiology & Oncology, Ljubljana", journal = "Radiology and Oncology", title = "Biological evaluation of transdichloridoplatinum( II) complexes with 3-and 4-acetylpyridine in comparison to cisplatin", volume = "47", number = "4", pages = "346-357", doi = "10.2478/raon-2013-0050" }
Filipović, L., Aranđelović, S., Gligorijević, N., Krivokuca, A., Jankovic, R., Srdić-Rajić, T., Rakic, G., Tešić, Ž. Lj.,& Radulović, S.. (2013). Biological evaluation of transdichloridoplatinum( II) complexes with 3-and 4-acetylpyridine in comparison to cisplatin. in Radiology and Oncology Assoc Radiology & Oncology, Ljubljana., 47(4), 346-357. https://doi.org/10.2478/raon-2013-0050
Filipović L, Aranđelović S, Gligorijević N, Krivokuca A, Jankovic R, Srdić-Rajić T, Rakic G, Tešić ŽL, Radulović S. Biological evaluation of transdichloridoplatinum( II) complexes with 3-and 4-acetylpyridine in comparison to cisplatin. in Radiology and Oncology. 2013;47(4):346-357. doi:10.2478/raon-2013-0050 .
Filipović, Lana, Aranđelović, Sandra, Gligorijević, Nevenka, Krivokuca, Ana, Jankovic, Radmila, Srdić-Rajić, Tatjana, Rakic, Gordana, Tešić, Živoslav Lj., Radulović, Siniša, "Biological evaluation of transdichloridoplatinum( II) complexes with 3-and 4-acetylpyridine in comparison to cisplatin" in Radiology and Oncology, 47, no. 4 (2013):346-357, https://doi.org/10.2478/raon-2013-0050 . .