Intercellular contact-dependent survival of human A549, NCI-H596 and NCI-H520 non-small cell lung carcinoma cell lines

Castro, Mauro A. A.; Schwartsmann, Gilberto; Moreira, José Cláudio Fonseca

doi:10.1590/s0100-879x2001000800006

Cited by 7 publications

(5 citation statements)

References 21 publications

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“…Controversial results concerning the effect of cell density, e.g. gap junction intercellular communication, on survival of cancer cells after treatment with DNA damaging agents including cisplatin are reported in the literature [ 29 – 31 ]. At the start of the 24 h cisplatin treatment, cell density was 2.7-fold higher after extensive pemetrexed pretreatment (treatment #3, day 2) compared to treatment #1 (day 0) (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…However, cell density was still >4 times below full confluence (Fig. 1b , untreated control, day 3), which is associated in NSCLC cell lines with DNA damage resistance [ 29 ]. Hence, an alternative experimental setting will be necessary to elucidate if survival after pretreatment with MTA prior to cisplatin challenge is significantly altered by variations in cell culture density.…”

Section: Discussionmentioning

confidence: 99%

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Prolonged pemetrexed pretreatment augments persistence of cisplatin-induced DNA damage and eliminates resistant lung cancer stem-like cells associated with EMT

et al. 2016

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BackgroundLung cancer is the leading cause of cancer-related mortality, and new therapeutic options are urgently needed. Non-small cell lung cancer (NSCLC) accounts for approximately 85 % of all lung cancers, with the current standard regimen of care for NSCLC including chemotherapy with pemetrexed as a single agent or in combination with platinum-based agents, e.g. cisplatin. Pemetrexed is a folic acid antagonist that inhibits the synthesis of precursor nucleotides, whereas cisplatin directly induces DNA adducts, the repair of which is dependent on sufficiently high nucleotide levels. In the clinical setting, the pemetrexed-cisplatin combination therapy is administered concomitantly. We hypothesized that prolonged pretreatment with pemetrexed could be beneficial, as prior depletion of nucleotide pools could sensitize cancer cells to subsequent treatment with cisplatin.MethodsNSCLC A549 and H460 cells were treated with pemetrexed for 72 h. In addition, 24 h of cisplatin treatment was initiated at day 1, 2 or 3 resulting in either simultaneous pemetrexed application or pemetrexed pretreatment for 24 or 48 h, respectively. Cell growth and colony formation as well as senescence induction were quantified after treatment. Cell cycle distribution and phosphorylation of histone variant H2AX as a surrogate marker for DNA damage was quantified by flow cytometry. Relative changes in gene expression were determined by quantitative real time PCR.ResultsProlonged pemetrexed pretreatment for 48 h prior to cisplatin treatment maximally delayed long-term cell growth and significantly reduced the number of recovering clones. Moreover, apoptosis and senescence were augmented and recovery from treatment-induced DNA damage was delayed. Interestingly, a cell population was identified that displayed an epithelial-to-mesenchymal transition (EMT) and which had a stem cell phenotype. This population was highly resistant to concomitant pemetrexed-cisplatin treatment but was sensitized by pemetrexed pretreatment.ConclusionsAdaptation of the standard treatment schedule to include pretreatment with pemetrexed optimizes the anticancer efficiency of pemetrexed-cisplatin combination therapy, which correlates with a persistence of treatment-induced DNA damage. Therefore, this study warrants further investigations to elucidate whether such an adaptation could enhance the effectiveness of the standard clinical treatment regimen. In addition, a subpopulation of therapy resistant cells with EMT and cancer stem cell features was identified that was resistant to the standard treatment regimen but sensitive to pemetrexed pretreatment combined with cisplatin.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2117-4) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Prolonged pemetrexed pretreatment augments persistence of cisplatin-induced DNA damage and eliminates resistant lung cancer stem-like cells associated with EMT

et al. 2016

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“…The difference in p53 function would lead to the prediction that H520 cells should be more resistant to agents that induce apoptosis. A study using ultraviolet (UV) radiation reported that H520 cells were indeed more resistant than the A549 cell line [27]. However, a recent study using ionizing radiation reported A549 cells were more resistant than H520 [28].…”

Section: Discussionmentioning

confidence: 99%

Jasmonates Induce Apoptosis and Cell Cycle Arrest in Non-Small Cell Lung Cancer Lines

Yeruva

Pierre

Carper

et al. 2006

Experimental Lung Research

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The jasmonates, cis-jasmone (CJ) and methyl jasmonate (MJ), were investigated for their effects against NSCLC cell lines A549 and H520. CJ or MJ inhibited the proliferation of both cell lines in a dose-dependent manner as well as induced cell cycle arrest in the G2/M phase. Apoptosis was observed following treatment with CJ or MJ as indicated by Hoechst staining and confirmed by dual annexin V-fluorescein isothiocyanate (FITC)/prodium iodide (PI) and DAPI (4',6-diamidine-2'-phenylindole dihydrochloride) staining. p38 and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation was observed with increased expression of bax, p21, and caspase-3 activity. These observations indicate that jasmonates may have a therapeutic value in the treatment of lung cancer.

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“…Among the central questions in tumour biology is the extent of the role of cell phenotype in modulation of cell growth (Folkmann & Moscona 1978;Ingber 1990;Chen et al 1997). In previous studies of three human non-small cell lung carcinoma cell lines (Castro et al 1999;Castro, Schwartsmann & Moreira 2001), we addressed the question of whether two-and three-dimensional growth followed a common growth dynamic. We have shown the use of morphometrical analysis to describe each cell line and concluded that the cells under study gave rise to phenotypic growth modulation as a function of cell density.…”

Section: Introductionmentioning

confidence: 99%

Gompertzian growth pattern correlated with phenotypic organization of colon carcinoma, malignant glioma and non‐small cell lung carcinoma cell lines

et al. 2003

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In the current study we present a Gompertzian model for cell growth as a function of cell phenotype using six human tumour cell lines (A-549, NCI-H596, NCI-H520, HT-29, SW-620 and U-251). Monolayer cells in exponential growth at various densities were quantified over a week by sulforhodamine B staining assay to produce cell-growth curves. A Gompertz equation was fitted to experimental data to obtain, for each cell line, three empirical growth parameters (initial cell density, cell-growth rate and carrying capacity - the maximal cell density). A cell-shape parameter named deformation coefficient D (a morphological relationship among spreading and confluent cells) was established and compared by regression analysis with the relative growth rate parameter K described by the Gompertz equation. We have found that coefficient D is directly proportional to the growth parameter K. The fit curve significantly matches the empirical data (P < 0.05), with a correlation coefficient of 0.9152. Therefore, a transformed Gompertzian growth function was obtained accordingly to D. The degree of correlation between the Gompertzian growth parameter and the coefficient D allows a new interpretation of the growth parameter K on the basis of morphological measurements of a set of tumour cell types, supporting the idea that cell-growth kinetics can be modulated by phenotypic organization of attached cells.

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Intercellular contact-dependent survival of human A549, NCI-H596 and NCI-H520 non-small cell lung carcinoma cell lines

Cited by 7 publications

References 21 publications

Prolonged pemetrexed pretreatment augments persistence of cisplatin-induced DNA damage and eliminates resistant lung cancer stem-like cells associated with EMT

Prolonged pemetrexed pretreatment augments persistence of cisplatin-induced DNA damage and eliminates resistant lung cancer stem-like cells associated with EMT

Jasmonates Induce Apoptosis and Cell Cycle Arrest in Non-Small Cell Lung Cancer Lines

Gompertzian growth pattern correlated with phenotypic organization of colon carcinoma, malignant glioma and non‐small cell lung carcinoma cell lines

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