dld1  (ATCC)

Journal: Neoplasia (New York, N.Y.)

Article Title: Metabolic regulation of histone acetylation by ACLY supports MDR1 expression in colorectal cancer and highlights a targetable vulnerability

doi: 10.1016/j.neo.2026.101314

Figure Lengend Snippet: ACLY activity regulates MDR1 expression in colorectal cancer. (A) Transcript levels of ACLY and MDR1 (ABCB1) in colorectal cancer (red) and normal colon tissues (grey) analyzed using GEPIA (TCGA/GTEx datasets). (B) Immunoblot analysis of MDR1 in SW480 and DLD1 cells treated with the ACLY inhibitor BMS-303141 (20 or 50 μM, 48 h). (C) Immunoblot analysis of ACLY and MDR1 in SW480 and DLD1 cells transduced with empty vector (pLV) or ACLY-overexpressing vector (pLV[Exp]-hACLY). (D) Immunoblot analysis of ACLY and MDR1 in control and ACLY-overexpressing cells treated with BMS-303141 (50 μM, 48 h). (E) Relative ABCB1 mRNA levels in control and ACLY-overexpressing cells, and in cells treated with BMS-303141. (F) Relative ACLY mRNA levels under the same conditions. Data are presented as mean ± SD (n = 3 unless otherwise indicated). Statistical significance was determined using unpaired two-tailed t-tests or one-way ANOVA with Tukey’s post hoc test. *P < 0.05; **P < 0.01; ***P < 0.001.

Article Snippet: Human colorectal cancer cell lines SW480 (KRASG12V) and DLD1 (KRASG13D) were obtained from the American Type Culture Collection (ATCC) and authenticated by short tandem repeat profiling.

Techniques: Activity Assay, Expressing, Western Blot, Transduction, Plasmid Preparation, Control, Two Tailed Test

Journal: Neoplasia (New York, N.Y.)

Article Title: Metabolic regulation of histone acetylation by ACLY supports MDR1 expression in colorectal cancer and highlights a targetable vulnerability

doi: 10.1016/j.neo.2026.101314

Figure Lengend Snippet: ACLY activity modulates histone acetylation and MDR1 expression. (A) Immunoblot analysis of MDR1 in SW480 and DLD1 cells treated with the histone deacetylase inhibitor vorinostat (VOR; 0.5 μM for SW480 and 3.5 μM for DLD1) or DMSO for 24 h. Representative blots and densitometric quantification relative to control are shown. (B) Immunoblot analysis of acetylated histone H3 (H3K9ac) and histone H4 (H4K16ac) in SW480 wild-type (WT) and ACLY-overexpressing (OE) cells treated with vehicle or the ACLY inhibitor BMS-303141 (50 μM, 48 h). (C) Immunoblot analysis of H3K9ac and H4K16ac in DLD1 cells under the same conditions. β-actin was used as a loading control. Data are presented as mean ± SD (n = 3). Statistical significance was determined using unpaired two-tailed t-tests. *P < 0.05; **P < 0.01; ***P < 0.001.

Article Snippet: Human colorectal cancer cell lines SW480 (KRASG12V) and DLD1 (KRASG13D) were obtained from the American Type Culture Collection (ATCC) and authenticated by short tandem repeat profiling.

Techniques: Activity Assay, Expressing, Western Blot, Histone Deacetylase Assay, Control, Two Tailed Test

Journal: Neoplasia (New York, N.Y.)

Article Title: Metabolic regulation of histone acetylation by ACLY supports MDR1 expression in colorectal cancer and highlights a targetable vulnerability

doi: 10.1016/j.neo.2026.101314

Figure Lengend Snippet: ACLY expression is associated with resistance-related transcriptional programs in colorectal cancer. (A) Correlation analysis between ACLY expression and a gene set associated with lipid metabolism (ACLY, ACSS2, ACSS1, FASN, SREBP1) and drug transport pathways (ABCB1, ABCC2, ABCG5, EpCAM, CD24) in colorectal cancer samples using GEPIA2 (TCGA dataset). (B) Schematic representation of a proposed model linking ACLY-dependent acetyl-CoA production to histone acetylation and transcriptional regulation in CRC cells. (C) Relative mRNA expression of EpCAM, ABCC2, and CD24 in SW480 and DLD1 cells overexpressing ACLY compared with empty vector controls. (D) Relative mRNA expression of EpCAM, ABCC2, and CD24 in SW480 and DLD1 cells treated with the ACLY inhibitor BMS-303141 (50 μM) compared with vehicle-treated controls. Gene expression levels were determined by qPCR and normalized to ACTB. Data are presented as mean ± SEM (n = 3). Statistical significance was determined using unpaired two-tailed t-tests. *P < 0.05; **P < 0.01; ***P < 0.001.

Article Snippet: Human colorectal cancer cell lines SW480 (KRASG12V) and DLD1 (KRASG13D) were obtained from the American Type Culture Collection (ATCC) and authenticated by short tandem repeat profiling.

Techniques: Expressing, Drug Transport Assay, Plasmid Preparation, Gene Expression, Two Tailed Test

Journal: Neoplasia (New York, N.Y.)

Article Title: Metabolic regulation of histone acetylation by ACLY supports MDR1 expression in colorectal cancer and highlights a targetable vulnerability

doi: 10.1016/j.neo.2026.101314

Figure Lengend Snippet: Vitamin C induces coordinated changes in metabolic and chromatin-associated pathways in colorectal cancer cells. (A) Gene Ontology (GO) enrichment analysis of proteins differentially expressed following vitamin C treatment (5 mM, 4 h). (B) Volcano plot showing significantly upregulated and downregulated proteins (log₂ fold change > 1, p < 0.05). (C) KEGG pathway enrichment analysis highlighting pathways related to chromatin organization, DNA replication, nucleotide metabolism, and cell cycle regulation. (D) GO Cellular Component analysis showing enrichment of chromatin-associated complexes, including transcription regulator complexes, histone acetyltransferase-containing complexes, and Polycomb group (PcG) assemblies. (E) Heatmap representation of differentially expressed chromatin-associated proteins in control and vitamin C-treated cells. Proteomic analysis was performed in SW480 and DLD1 cells using label-free LC–MS/MS (diaPASEF). Data represent combined analysis of both cell lines.

Article Snippet: Human colorectal cancer cell lines SW480 (KRASG12V) and DLD1 (KRASG13D) were obtained from the American Type Culture Collection (ATCC) and authenticated by short tandem repeat profiling.

Techniques: Control, Liquid Chromatography with Mass Spectroscopy, Data-independent acquisition

Journal: Neoplasia (New York, N.Y.)

Article Title: Metabolic regulation of histone acetylation by ACLY supports MDR1 expression in colorectal cancer and highlights a targetable vulnerability

doi: 10.1016/j.neo.2026.101314

Figure Lengend Snippet: Metabolic and epigenetic consequences of vitamin C treatment in colorectal cancer cells. (A) Quantification of ¹³C-glucose-derived citrate in SW480 and DLD1 cells treated with vitamin C (5 mM) for 4 h (n = 3). (B) Immunoblot analysis of total ACLY and phosphorylated ACLY at Ser455 following vitamin C treatment (5 mM) (n = 3). (C) Immunoblot analysis and quantification of acetylated histone H4 (AcH4K16) and histone H3 (AcH3K9) in SW480 and DLD1 cells after vitamin C exposure (n = 3). (D) MDR1 (ABCB1) protein levels in SW480 and DLD1 cells treated with vitamin C (5 mM), quantified relative to vehicle control (n = 3). (E) Relative ACLY and ABCB1 mRNA expression determined by qPCR after 6 h of vitamin C treatment (5 mM) in SW480 and DLD1 cells (n = 3). Data are presented as mean ± SEM. Statistical significance was determined using unpaired two-tailed t-tests. *P < 0.05; **P < 0.01; ***P < 0.001.

Article Snippet: Human colorectal cancer cell lines SW480 (KRASG12V) and DLD1 (KRASG13D) were obtained from the American Type Culture Collection (ATCC) and authenticated by short tandem repeat profiling.

Techniques: Derivative Assay, Western Blot, Control, Expressing, Two Tailed Test