Modulation of Pathways Underlying Distinct Cell Death Mechanisms in Two Human Lung Cancer Cell Lines in Response to SN1 Methylating Agents Treatment

Papadodima, Olga; Moulos, Panagiotis; Koryllou, Aggeliki; Piroti, Georgia; Kolisis, Fragiskos N.; Chatziioannou, Aristotelis; Pletsa, Vasiliki

doi:10.1371/journal.pone.0160248

Cited by 2 publications

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“…Our findings, overall, indicate replication fork collapse due to DPS-2 treatment, still, further investigation is needed to understand how the compound affects the signaling pathways involved in cellular survival and death, in particular in view of DPS-2’s development as a novel chemotherapeutic drug. Chemotherapeutic agents may activate various modes of cell death and, in general, the cell death pathways finally activated following the interplay of pro-survival and pro-death signaling depend on the cellular background [17,44]. In cancer cell systems, the evasion of cell death being one of the major hallmarks, this interplay becomes even more complicated [20].…”

Section: Discussionmentioning

confidence: 99%

Oil-In-Water Microemulsions as Hosts for Benzothiophene-Based Cytotoxic Compounds: An Effective Combination

et al. 2018

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Targeted delivery of chemotherapeutics in order to overcome side effects and enhance chemosensitivity remains a major issue in cancer research. In this context, biocompatible oil-in-water (O/W) microemulsions were developed as matrices for the encapsulation of DPS-2 a benzothiophene analogue, exhibiting high cytotoxicity in various cancer cell lines, among them the MW 164 skin melanoma and Caco-2 human epithelial colorectal adenocarcinoma cell lines. The microemulsion delivery system was structurally characterized by dynamic light scattering (DLS) and electron paramagnetic resonance (EPR) spectroscopy. The effective release of a lipophilic encapsulated compound was evaluated via confocal microscopy. The cytotoxic effect, in the presence and absence of DPS-2, was examined through the thiazolyl blue tetrazolium bromide (MTT) cell proliferation assay. When encapsulated, DPS-2 was as cytotoxic as when dissolved in dimethyl sulfoxide (DMSO). Hence, the oil cores of O/W microemulsions were proven effective biocompatible carriers of lipophilic bioactive molecules in biological assessment experiments. Further investigation through fluorescence-activated cell sorting (FACS) analysis, comet assay, and Western blotting, revealed that DPS-2, although non-genotoxic, induced S phase delay accompanied by cdc25A degradation and a nonapoptotic cell death in both cell lines, which implies that this benzothiophene analogue is a deoxyribonucleic acid (DNA) replication inhibitor.

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Section: Discussionmentioning

confidence: 99%

Oil-In-Water Microemulsions as Hosts for Benzothiophene-Based Cytotoxic Compounds: An Effective Combination

et al. 2018

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Correction: Modulation of Pathways Underlying Distinct Cell Death Mechanisms in Two Human Lung Cancer Cell Lines in Response to SN1 Methylating Agents Treatment

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2018

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The PLOS ONE Journal StaffThe Abstract section is missing. The publisher apologizes for the error. The Abstract can be viewed here: AbstractDespite concerted research efforts, lung cancer remains the leading cause of cancer death worldwide, therefore, new therapeutic approaches are eagerly needed. Methylating agents of S N 1 type constitute a widely used class of anticancer drugs, the effect of which on human non small-cell lung cancer (NSCLC) has not been adequately studied although frequently combined with platinum-based chemotherapy. We thus studied the effect of N-methyl-Nnitrosourea (MNU), a model S N 1 methylating agent, on two human NSCLC cell lines; A549 (p53 wt ) and H157 (p53 null ). The mechanism of MNU-induced cell death was investigated

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Modulation of Pathways Underlying Distinct Cell Death Mechanisms in Two Human Lung Cancer Cell Lines in Response to SN1 Methylating Agents Treatment

Cited by 2 publications

References 53 publications

Oil-In-Water Microemulsions as Hosts for Benzothiophene-Based Cytotoxic Compounds: An Effective Combination

Oil-In-Water Microemulsions as Hosts for Benzothiophene-Based Cytotoxic Compounds: An Effective Combination

Correction: Modulation of Pathways Underlying Distinct Cell Death Mechanisms in Two Human Lung Cancer Cell Lines in Response to SN1 Methylating Agents Treatment

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