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Publikation

Hübner, D.; Kaluđerović, M. R.; Gómez-Ruiz, S.; Kaluđerović, G. N.; Anionic chlorido(triphenyl)tin(IV) bearing N-phthaloylglycinato or 1,2,4-benzenetricarboxylato 1,2-anhydride ligands: potential cytotoxic and apoptosis-inducing agents against several types of cancer Chem. Biol. Drug Des. 89, 628-633, (2017) DOI: 10.1111/cbdd.12885

Two ionic triphenyltin(IV) chloride carboxylate compounds of the formula [NHEt3][Ph3SnCl(L)] [LH = N‐phthaloylglycine (P‐GlyH), 1; 1,2,4‐benzenetricarboxylic 1,2‐anhydride (BTCH), 2] were tested for the in vitro activity against 518A2 (melanoma), FaDu (head and neck carcinoma), HT‐29 (colon cancer), MCF‐7 (breast carcinoma), and SW1736 (thyroid cancer) cell lines. The ammonium salts of the carboxylic acids are found to be not active, while anionic [Ph3SnCl(L)]− exhibited high cytotoxicity in nM range, both higher activity and selectivity than cisplatin. Compounds 1 and 2 are inducing apoptosis, which was proved with the morphological and biochemical features such as membrane blebbing, translocation of phosphatidylserine, and DNA fragmentation. Thus, accumulation of cells in sub‐G1 phase is observed. Both anionic organotin(IV) compounds showed potent cytotoxic and apoptotic properties against five cancer cell lines of various histogenetic origin.
Publikation

Edeler, D.; Kaluđerović, M. R.; Dojčinović, B.; Schmidt, H.; Kaluđerović, G. N.; SBA-15 mesoporous silica particles loaded with cisplatin induce senescence in B16F10 cells RSC Adv. 6, 111031-111040, (2016) DOI: 10.1039/C6RA22596A

The anticancer drug cisplatin (CP) is loaded into SBA-15 mesoporous silica (SBA-15|CP) and its release from the nanomaterial is studied. The CP-loaded SBA-15 is tested against four tumor cell lines: mouse malignant melanoma B16F10, human adenocarcinoma HeLa, colon HT-29 and prostate PC3. Most importantly, the superiority of this novel material in comparison to CP arises from the fact that the CP-grafted nanomaterial SBA-15 (→SBA-15|CP) is enhancing cessation of proliferation along with induction of senescence in B16F10 in approximately 3.5 times lower concentration. The control material loaded with therapeutically inactive K2[PtCl4] (→SBA-15|TC) showed no antitumor activity. To a large extent, SBA-15|CP-induced senescence might present a safe approach in tumor treatment. Such cells can be cleared by immune cells resulting in efficient tumor regression. So far only apoptotic agents are being exploited in clinics, thus an understanding of the chemotherapeutic-induced senescence will allow oncologists to explore this essential tumor suppressor mechanism.
Publikation

Bulatović, M.; Kaluđerović, M. R.; Mojić, M.; Zmejkovski, B. B.; Hey-Hawkins, E.; Vidaković, M.; Grdović, N.; Kaluđerović, G. N.; Mijatović, S.; Maksimović-Ivanić, D.; Improved in vitro antitumor potential of (O,O′-Diisobutyl-ethylenediamine-N,N′-di-3-propionate)tetrachloridoplatinum(IV) complex under normoxic and hypoxic conditions Eur. J. Pharmacol. 760, 136-144, (2015) DOI: 10.1016/j.ejphar.2015.04.012

(O,O′-Diisobutyl-ethylenediamine-N,N′-di-3-propionate)tetrachloridoplatinum(IV), [PtCl4(iBu2eddp)], shows an improved pharmacological profile in comparison to cisplatin. This is manifested through accelerated dying process led by necrotic cell death, reflected through mitochondrial collapse, strong ATP depletion and reactive oxygen species production. Loss of mitochondrial potential was further followed with intensive apoptosis that finalized with DNA fragmentation.Different dynamic of tumoricidal action could be partly ascribed to less affected repair mechanisms in comparison to cisplatin. Importantly, [PtCl4(iBu2eddp)] did not induce necrosis in primary fibroblasts suggesting different intracellular response of normal vs. tumor cells. This selectivity toward malignant phenotype is further confirmed by retained tumoricidal potential in hypoxic conditions, while cisplatin became completely inefficient.

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