Subcellular localization of proflavine derivative and induction of oxidative stress—In vitro studies

Ipóthová, Z; Paulíková, Helena; Čižeková, Lýdia; Hunáková, Ľuba; Labudová, Martina; Grolmusová, A.; Janovec, Ladislav; Imrich, Ján

doi:10.1016/j.bmc.2013.08.007

Cited by 6 publications

(3 citation statements)

References 13 publications

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“…Although acridine derivatives are known as mutagens [61][62], not all of them can enter the nuclei [28,[63][64][65][66]. Propyl-AcrDTU was not located in the nuclei of L1210/VCR cells, although partial relocalization of AcrDTU to the nuclei was observed after irradiation of the treated cells.…”

Section: Discussionmentioning

confidence: 92%

Photodynamic therapy of multidrug resistant leukemic murine cells by 3,6-bis(alkylthiourea)acridine hydrochlorides

Paulíková¹,

Cisáriková²,

Bačová³

et al. 2021

neo

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Efforts to overcome multidrug resistance in cancer have led to the development of several novel strategies including photodynamic therapy (PDT). PDT is based on the use of photosensitizers (PSs) photoactivation, which causes the formation of reactive oxygen species that can induce cell death. In the last decade, the development of new PSs has been significantly accelerated. Recently, acridine-3,6-dialkyldithiourea hydrochlorides (AcrDTUs) have been investigated as a new group of PSs and we have shown that PDT/AcrDTUs caused cell death of mouse leukemic cells L1210. In this study, we investigated the efficacy of PDT/AcrDTUs for the treatment of L1210/VCR cells as a model of chemo-resistant cells (overexpressing P-glycoprotein, P-gp). The photoactivation (365 nm, 1.05 J/cm2) increased the cytotoxicity of AcrDTUs 10 -15 times. Inhibition of P-gp (verapamil) has been shown to have no significant effect on the accumulation of propyl-AcrDTU (the most potent derivative) in L1210/VCR cells. The intracellular distribution of this acridine derivative has been studied. Prior to irradiation of the resistant cells, propyl-AcrDTU was sequestered mainly in the cytosol, partly in the mitochondria, and, unlike in the sensitive cells, the AcrDTU was not found in the lysosomes. PDT with 1 µM propyl-AcrDTU induced cell shrinkage and "ladder DNA" formation, and although a drastic decrease of the intracellular ATP level was observed at the same time, there was no increase in extracellular LDH activity. AIF in the nucleus can induce DNA fragmentation and we have actually observed a mitochondrio-nuclear translocation of AIF. We concluded that AcrDTUs are photocytotoxic against L1210/VCR cells and that mitochondria play an important role in cell death induced by PDT.

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Section: Discussionmentioning

confidence: 92%

Photodynamic therapy of multidrug resistant leukemic murine cells by 3,6-bis(alkylthiourea)acridine hydrochlorides

Paulíková¹,

Cisáriková²,

Bačová³

et al. 2021

neo

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“…Such types of acridines were prepared in our laboratory [33][34][35]. It was proven that 3,6-bis((1-n-alkyl-5-oxo-imidazolidin-2-yliden) imino)acridine hydrochlorides were localized in mitochondria [36]. Likewise, unusual non-nuclear accumulation of 3-amino-4-hydroxymethyl-acridine derivative in the form of aggregates in the cytoplasm accompanied by its localization also in lysosomes was found out by Peixoto et al in 2009 [37].…”

Section: Discussionmentioning

confidence: 99%

Intracellular distribution of 3,6-bis(3-alkylguanidino)acridines determines their cytotoxicity

L¹,

Paulíková²,

Bačová³

et al. 2015

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Cytotoxicity of two derivatives of 3,6-bis(3-alkylguanidino)acridines (GNDAs; pentyl-and hexyl-GNDA) was determined against three cell lines: a murine immortalized fibroblast cell line NIH-3T3, a human ovarian carcinoma cell line A2780, and a human neuroblastoma cell line SH-SY5Y. We found out that these GNDAs were cytotoxic against A2780 and NIH-3T3 cells but they showed only a marginal cytotoxicity against neuroblastoma cells SH-SY5Y. To explain differences in cytotoxicity, intracellular distribution of GNDAs was monitored. GNDAs were accumulated in A2780 and NIH-3T3 cells in the nuclei (fluorescence microscopy). In contrast to these cell lines, in SH-SY5Y cells, GNDAs were localized outside of the nuclei, at the plasma membrane and surroundings, extending also to the cytosol. This distribution of GNDAs was confirmed by an ImageStream Flow Cytometer. Acetylcholinesterase (AChE) activity in the SH-SY5Y cells decreased upon incubation with GNDAs. Kinetic studies showed that GNDAs were able to inhibit AChE by the same mode as tacrine (9-amino-1,2,3,4-tetrahydroacridine), a known inhibitor of AChE. A low cytotocity of GNDAs against SH-SY5Y cells could be caused by their affinity to AChE (the enzyme is localized mainly at the plasma membrane). The interaction of GNDAs with AChE may affect their intracellular distribution and consequently the cytotoxicity.

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“…Photocytotoxicity of two groups of derivatives, 3,6-bis((1-alkyl-5-oxo-imidazolidin-2-yliden) imino)acridine hydrochlorides (AcrDIMs) and 1',1"-(acridin-3,6)-3',3"-diyldithiourea hydrochlorides (AcrDTUs), was studied by Čižeková et al (2014) and Grolmusová et al (2015). Intracellular distribution and cytotoxicity of AcrDIMs against A2780 cells and other cell lines was evaluated by Janovec et al (2011) and Ipóthová et al (2013). EPR measurements showed that superoxide radical anion and singlet oxygen were produced after irradiation (UV-A, >300 nm) of AcrDIM and AcrDTU derivatives (Grolmusová et al, 2013;Čižeková et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Photocleavage of pDNA by bis-imidazolidino and bis-thioureido proflavines

Cisárikováa

Abaffy

Imrich

et al. 2015

Acta Chimica Slovaca

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New photosensitizers are needed for photodynamic antimicrobial and anticancer chemotherapy. Two new groups of proflavine derivatives have been recently prepared and their action on the cancer cells has been investigated by our research team. In this paper, we studied an effect of UV-A irradiation of two groups of proflavines: 3,6-bis((1-alkyl-5-oxo-imidazolidin-2-yliden)imino)acridine hydrochlorides (AcrDIMs) and 1’,1”-(acridin-3,6-diyl)-3’,3”-dialkyldithiourea hydrochlorides (AcrDTUs) on a plasmid DNA (pDNA). These compounds induced a photocleavage of pDNA characteristic by generation of free radicals, single strand DNA breaks and formation of an open circular form of pDNA.

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Subcellular localization of proflavine derivative and induction of oxidative stress—In vitro studies

Cited by 6 publications

References 13 publications

Photodynamic therapy of multidrug resistant leukemic murine cells by 3,6-bis(alkylthiourea)acridine hydrochlorides

Photodynamic therapy of multidrug resistant leukemic murine cells by 3,6-bis(alkylthiourea)acridine hydrochlorides

Intracellular distribution of 3,6-bis(3-alkylguanidino)acridines determines their cytotoxicity

Photocleavage of pDNA by bis-imidazolidino and bis-thioureido proflavines

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