Additional file 5: Figure S4. of EGFR is not a major driver for osteosarcoma cell growth in vitro but contributes to starvation and chemotherapy resistance

Impact of EGFR inhibition by gefitinib on cell cycle distribution. The indicated osteosarcoma cell lines were treated with gefitinib (1 μM, 5 μM and 10 μM) for 24 h in 1 % FCS containing culture medium and opposed to untreated cells at 10 % FCS (control). Cell cycle distribution was analysed by PI staining followed by FACS analysis. (PDF 56 kb

Additional file 3: Figure S2. of EGFR is not a major driver for osteosarcoma cell growth in vitro but contributes to starvation and chemotherapy resistance

Impact of EGF and EGFR inhibition on starvation survival of osteosarcoma cells with comparably high (A) and low (B) EGFR expression levels. Viability of osteosarcoma cells was determined by MTT assays after 72 h serum starvation (1 % or 0.1 % FCS) under increasing EGF concentrations without or with gefitinib (5 μM) as indicated. Significance of the gefitinib impact: ** p < 0.01; *** p < 0.001 by Two-way ANOVA with Bonferroni’s post hoc test. (PDF 71 kb

New 5‑Aryl‑1<i>H</i>‑imidazoles Display in Vitro Antitumor Activity against Apoptosis-Resistant Cancer Models, Including Melanomas, through Mitochondrial Targeting

We designed and synthesized 48 aryl-1<i>H</i>-imidazole derivatives and investigated their in vitro growth inhibitory activity in cancer cell lines known to present various levels of resistance to proapoptotic stimuli. The IC₅₀ in vitro growth inhibitory concentration of these compounds ranged from >100 μM to single digit μM. Among the most active compounds, <b>2i</b> displayed similar in vitro growth inhibition in cancer cells independent of the cells’ levels of resistance to proapoptotic stimuli and was found to be cytostatic in melanoma cell lines. Compound <b>2i</b> was then tested by the National Cancer Institute Human Tumor Cell Line Anti-Cancer Drug Screen, and the NCI COMPARE algorithm did not reveal any correlation between its growth inhibition profiles with the NCI database compound profiles. The use of transcriptomically characterized melanoma models then enabled us to highlight mitochondrial targeting by <b>2i</b>. This hypothesis was further confirmed by reactive oxygen production measurement and oxygen consumption analysis

Additional file 3: Table S2. of Intrinsic fluorescence of the clinically approved multikinase inhibitor nintedanib reveals lysosomal sequestration as resistance mechanism in FGFR-driven lung cancer

Impact of lysosomal alkalization by bafilomycin A1 on nintedanib fluorescence. (DOCX 14 kb

Additional file 2: Figure S1. of Intrinsic fluorescence of the clinically approved multikinase inhibitor nintedanib reveals lysosomal sequestration as resistance mechanism in FGFR-driven lung cancer

Lysosomal alkalization selectively abrogates green fluorescence activity of nintedanib in DMS114 and NCI-H520 cells. (PPTX 1566 kb

Additional file 4: Figure S2. of Intrinsic fluorescence of the clinically approved multikinase inhibitor nintedanib reveals lysosomal sequestration as resistance mechanism in FGFR-driven lung cancer

Lysosomal alkalization leads to sensitization towards nintedanib. (PPTX 335 kb

Additional file 5: Figure S3. of Intrinsic fluorescence of the clinically approved multikinase inhibitor nintedanib reveals lysosomal sequestration as resistance mechanism in FGFR-driven lung cancer

Crystalline nintedanib exhibits both blue and green fluorescence properties. Cell-free nintedanib fluorescence properties in crystalline form or dissolved in DMSO were analyzed by fluorescence microscopy using DIC, FITC and DAPI channels. (PPTX 718 kb