New insight into the molecular mechanisms of the biological effects of DNA minor groove binders.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:21998702", "kind": "science-record", "revision": 7, "content_hash": "sha256:266abf8683fc5ee1a35b62514a4531dd8fcd3de6d219ce3086cb3f54ad36d786", "created_at": "2026-11-01T15:40:02Z", "updated_at": "2026-11-01T21:58:08Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "New insight into the molecular mechanisms of the biological effects of DNA minor groove binders.", "doi": "10.1371/journal.pone.0025822", "pmid": "21998702", "authors": ["Xinbo Zhang", "Siyu Crystal Zhang", "Dejun Sun", "Jiang Hu", "Anil Wali", "Harvey Pass", "Felix Fernandez-Madrid", "Michael R Harbut", "Naimei Tang"], "journal": "PloS one", "year": 2011, "abstract": "BACKGROUND: Bisbenzimides, or Hoechst 33258 (H258), and its derivative Hoechst 33342 (H342) are archetypal molecules for designing minor groove binders, and widely used as tools for staining DNA and analyzing side population cells. They are supravital DNA minor groove binders with AT selectivity. H342 and H258 share similar biological effects based on the similarity of their chemical structures, but also have their unique biological effects. For example, H342, but not H258, is a potent apoptotic inducer and both H342 and H258 can induce transgene overexpression in in vitro studies. However, the molecular mechanisms by which Hoechst dyes induce apoptosis and enhance transgene overexpression are unclear.\nMETHODOLOGY/PRINCIPAL FINDINGS: To determine the molecular mechanisms underlying different biological effects between H342 and H258, microarray technique coupled with bioinformatics analyses and multiple other techniques has been utilized to detect differential global gene expression profiles, Hoechst dye-specific gene expression signatures, and changes in cell morphology and levels of apoptosis-associated proteins in malignant mesothelioma cells. H342-induced apoptosis occurs in a dose-dependent fashion and is associated with morphological changes, caspase-3 activation, cytochrome c mitochondrial translocation, and cleavage of apoptosis-associated proteins. The antagonistic effect of H258 on H342-induced apoptosis indicates a pharmacokinetic basis for the two dyes' different biological effects. Differential global gene expression profiles induced by H258 and H342 are accompanied by unique gene expression signatures determined by DNA microarray and bioinformatics software, indicating a genetic basis for their different biological effects.\nCONCLUSIONS/SIGNIFICANCE: A unique gene expression signature associated with H342-induced apoptosis provides a new avenue to predict and classify the therapeutic class of minor groove binders in the drug development process. Further analysis of H258-upregulated genes of transcription regulation may identify the genes that enhance transgene overexpression in gene therapy and promote recombinant protein products in biopharmaceutical companies.\nDATA DEPOSITION: The microarray data reported in this article have been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (accession no.GSE28616).", "claims": [{"id": "claim-method", "statement": "Combination index (CI) method adapted for in vitro drug testing was used to determine the nature of interaction between the two agents as described previously [57]. CI was generated from MTT data by CalcuSyn software (Biosoft).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:21998702", "locator": "sections[12] \"Analysis of interaction between H342 and H258\" paragraph 2", "quote": "Combination index (CI) method adapted for in vitro drug testing was used to determine the nature of interaction between the two agents as described previously [57]. CI was generated from MTT data by CalcuSyn software (Biosoft)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The microarray data reported in this article have been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (accession no.GSE28616).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:21998702", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "The microarray data reported in this article have been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (accession no.GSE28616)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The paper used Student's t-test, with P-values <0.05 considered significant, and deposited the microarray data in the Gene Expression Omnibus database under accession no. 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DATA DEPOSITION: The microarray data reported in this article have been depo", "rimer sequences used for real-time RT-PCR in microarray validation analysis.(DOC)Click here for addi"], "order_basis": "paper_text_order:897", "id": "assay:2"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["ns after fractionating the mitochondria from cultured H2373 MPM cells. 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