Cytotoxic action of maleimide derivative 1-(4-Cl-benzyl)-3-chloro-4-(CF(3)-phenylamino)-1H-pyrrole-2,5-dione toward mammalian tumor cells and its capability to interact with DNA

Finiuk, Nataliya; Ivasechko, Iryna; Klyuchivska, Olga; Kuznietsova, H.M.; Rybal’chenko, V. K.; Stoika, Rostyslav

doi:10.15407/ubj92.04.055

Cited by 3 publications

(8 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the previous study, we showed that MI-1 possessed a toxic action towards tumor cells of different origin (cervix, colon, breast, liver, pancreatic carcinomas). The most prominent effect was demonstrated at treatment of human cervix carcinoma (KB3-1 and KBC-1) and human colon carcinoma (HCT116) cells [10]. In this study, we have demonstrated that MI-1 induced the activation of caspase 3 via its cleavage in the treated HCT116 cells.…”

Section: Discussionmentioning

confidence: 53%

“…Recently, we have demonstrated that MI-1 possessed high cytotoxicity towards human colon carcinoma HCT116 cells with the IC 50 of 0.9 µg/mL. The IC 50 value of Dox for these cells equaled 0.8 µg/mL [10]. The 0.9 µg/mL concentration of MI-1 and Dox was chosen as a working dose at Western-blot analysis of their pro-apoptotic effects in HCT116 cells.…”

Section: Resultsmentioning

confidence: 99%

“…Western-blot analysis. Human colon carcinoma HCT116 cells were treated with MI-1 or Dox at 0.9 µg/mL that corresponds to thе IC 50 of these compounds for HCT116 cells [10]. The final concentration of the DMSO solvent was 0.005 % in the medium with 0.9 µg/mL of MI-1.…”

Section: Methodsmentioning

confidence: 99%

“…Besides, it demonstrated a toxic action towards cultured cells of different tumors (cervix, colon, breast, liver, pancrea tic carcinomas) with the inhibition concentration (IC 50 ) ranging from 0.8 to 18 µg/mL depen ding on tissue origin of the targeted cells. The most prominent effect was detected towards human cervix carcinoma (KB3-1 and KBC-1) and human colon carcinoma (HCT116) cells [10]. However, the mechanism of the anti-proliferative action of MI-1 was not studied.…”

Section: Introductionmentioning

confidence: 97%

See 3 more Smart Citations

Inhibitor of protein kinases 1-(4-chlorobenzyl)-3-chloro-4-(3-trifluoromethylphenylamino)-1Н-pyrrole-2,5-dione induces DNA damage and apoptosis in human colon carcinoma cells

Finiuk¹,

Klyuchivska²,

Kuznietsova³

et al. 2020

Biol. Stud.

Self Cite

View full text Add to dashboard Cite

Background. The heterocyclic scaffolds are in the list of key structural blocks used at synthesis of novel biologically active compounds. Materials and Methods. The present study addressed the evaluation of the mechanisms of the DNA damaging and pro-apoptotic actions in vitro of the maleimide derivative 1-(4-chlorobenzyl)-3-chloro-4-(3-trifluoromethylphenylamino)-1Н-pyrrole-2,5-dione (MI-1) targeting human colon carcinoma cells of HCT116 line. The Western-blot analysis was used to study changes in apoptosis-associated proteins, DNA comet assay under alkaline conditions was applied for evaluation of the DNA-damaging events, and Barton’s assay with diphenylamine was applied for measuring the level of DNA fragmentation in human colon carcinoma cells treated with MI-1 compound. Results. The results of the Western-blot analysis demonstrated that MI-1 induced the apoptosis in HCT116 cells via mitochondria-dependent pathway. It activated caspase 3 via its cleavage in the treated human colon carcinoma cells. Besides, MI-1 increased the content of mitochondria-specific proteins: endonuclease G (EndoG) and the pro-apoptotic cytosolic protein protease-activating factor 1 (Apaf1). At the same time, MI-1 reduced the level of the anti-apoptotic Bcl-2 protein in HCT116 cells. The DNA comet analysis under alkaline conditions of the targeted human colon carcinoma cells of HCT116 line demonstrated that MI-1 induced DNA single-strand breaks in line with the olive tail moment of 13.2. The results of the colorimetric diphenylamine assay in HCT116 cells have shown that cell treatment with MI-1 increased the content of fragmented DNA to 14.2 %. Conclusions. The anti-proliferative action of MI-1 in human colon carcinoma cells of HCT116 line is associated with apoptosis induction via mitochondria-dependent pathway, as well as the DNA damage through single-strand breaks and DNA fragmentation. These data suggest that the 1-(4-chlorobenzyl)-3-chloro-4-(3-trifluoromethylphenylamino)-1Н-pyrrole-2,5-dione (MI-1) might be a promising agent for suppression of growth of colon tumor cells. Keywords: 1Н-pyrrole-2,5-diones, apoptosis, Western-blot assay, comet assay, single-strand breaks, Barton’s assay, DNA fragmentation

show abstract

Section: Discussionmentioning

confidence: 53%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

See 2 more Smart Citations

Inhibitor of protein kinases 1-(4-chlorobenzyl)-3-chloro-4-(3-trifluoromethylphenylamino)-1Н-pyrrole-2,5-dione induces DNA damage and apoptosis in human colon carcinoma cells

Finiuk¹,

Klyuchivska²,

Kuznietsova³

et al. 2020

Biol. Stud.

Self Cite

View full text Add to dashboard Cite

show abstract

“…The MI-1 also demonstrated the anti-inflammatory activity [25]. The anti-cancer activity of the MI-1 was shown in the in vitro [24,[26][27][28] and in vivo experiments [29][30][31][32]. However, poor water solubility remains a big drawback of the biomedical application of the MI-1 that hinders its application as a medicinal remedy.…”

Section: Introductionmentioning

confidence: 99%

Antineoplastic Activity of Water-Soluble Form of Novel Kinase Inhibitor 1-(4-Chlorobenzyl)-3-chloro-4-(3-trifluoromethylphenylamino)-1H-pyrrole-2,5-dione immobilized on Polymeric Poly(PEGMA-co-DMM) Carrier

et al. 2022

View full text Add to dashboard Cite

The maleimide derivative 1-(4-chlorobenzyl)-3-chloro-4-(3-trifluoromethylphenylamino)-1H-pyrrole-2,5-dione (MI-1) was synthesized as inhibitor of several protein kinases, however, its application is hindered by its poor water solubility. In this study, the mechanisms of the antineoplastic action of MI-1 and its MI-1/M5 complex with M5 carrier (poly (PEGMA-co-DMM)) towards human colon carcinoma HCT116 cells were investigated by using the MTT and clonogenic assays, DNA intercalation with methyl green replacement, alkaline DNA comet assay, and Western-blot analysis. MI-1 compound and its MI-1/M5 complex possessed high toxicity towards colon (HCT116), cervical (HeLa) carcinoma cells and melanoma (SK-MEL-28) cells with GI50 value in a range of 0.75–7.22 µg/mL, and demonstrated high selectivity index (SI ˃ 6.9). The p53 status of colon cancer cells did not affect the sensitivity of these cells to the treatment with MI-1 and its MI-1/M5 complex. M5 polymer possessed low toxicity towards studied cells. The MI-1, MI-1/M5, and M5 only slightly inhibited growth of the pseudo-normal HaCaT and Balb/c 3T3 cell lines (GI50 ˃ 50 μg/mL). The MI-1 and its MI-1/M5 complex induced mitochondria-dependent pathway of apoptosis, damage of the DNA, and morphological changes in HCT116 cells, and affected the G2/M transition checkpoint. The MI-1 intercalated into the DNA molecule, while such capability of MI-1/M5 complex and M5 polymer was much lower. Thus, poly (PEGMA-co-DMM) might be a promising carrier for delivery of the maleimide derivative, MI-1, a novel kinase inhibitor, through improving its solubility in aqueous media and enhancing its antiproliferative action towards human tumor cells. Studies are in progress on the treatment of Nemeth-Kellner lymphoma (NK/Ly)-bearing mice with the MI-1 and MI-1/M5 complex.

show abstract

Suppression of systemic inflammation and signs of acute and chronic cholangitis by multi-kinase inhibitor 1-(4-Cl-benzyl)-3-chloro-4-(CF3-phenylamino)-1H-pyrrole-2,5-dione

et al. 2021

View full text Add to dashboard Cite

Cytotoxic action of maleimide derivative 1-(4-Cl-benzyl)-3-chloro-4-(CF(3)-phenylamino)-1H-pyrrole-2,5-dione toward mammalian tumor cells and its capability to interact with DNA

Cited by 3 publications

References 24 publications

Inhibitor of protein kinases 1-(4-chlorobenzyl)-3-chloro-4-(3-trifluoromethylphenylamino)-1Н-pyrrole-2,5-dione induces DNA damage and apoptosis in human colon carcinoma cells

Inhibitor of protein kinases 1-(4-chlorobenzyl)-3-chloro-4-(3-trifluoromethylphenylamino)-1Н-pyrrole-2,5-dione induces DNA damage and apoptosis in human colon carcinoma cells

Antineoplastic Activity of Water-Soluble Form of Novel Kinase Inhibitor 1-(4-Chlorobenzyl)-3-chloro-4-(3-trifluoromethylphenylamino)-1H-pyrrole-2,5-dione immobilized on Polymeric Poly(PEGMA-co-DMM) Carrier

Suppression of systemic inflammation and signs of acute and chronic cholangitis by multi-kinase inhibitor 1-(4-Cl-benzyl)-3-chloro-4-(CF3-phenylamino)-1H-pyrrole-2,5-dione

Contact Info

Product

Resources

About