دورية أكاديمية
أعرض في EDS

Synergistic Cytotoxicity of Histone Deacetylase and Poly-ADP Ribose Polymerase Inhibitors and Decitabine in Breast and Ovarian Cancer Cells: Implications for Novel Therapeutic Combinations.

التفاصيل البيبلوغرافية
العنوان: Synergistic Cytotoxicity of Histone Deacetylase and Poly-ADP Ribose Polymerase Inhibitors and Decitabine in Breast and Ovarian Cancer Cells: Implications for Novel Therapeutic Combinations.
المؤلفون: Valdez BC; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA., Tsimberidou AM; Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA., Yuan B; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA., Baysal MA; Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA., Chakraborty A; Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA., Andersen CR; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Andersson BS; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
المصدر: International journal of molecular sciences [Int J Mol Sci] 2024 Aug 26; Vol. 25 (17). Date of Electronic Publication: 2024 Aug 26.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, [2000-
مواضيع طبية MeSH: Decitabine*/pharmacology , Drug Synergism* , Histone Deacetylase Inhibitors*/pharmacology , Ovarian Neoplasms*/drug therapy , Ovarian Neoplasms*/metabolism , Ovarian Neoplasms*/pathology , Phthalazines*/pharmacology , Poly(ADP-ribose) Polymerase Inhibitors*/pharmacology , Breast Neoplasms*/drug therapy , Breast Neoplasms*/pathology , Breast Neoplasms*/metabolism , Cell Proliferation*/drug effects , Piperazines*/pharmacology, Humans ; Female ; Cell Line, Tumor ; Vorinostat/pharmacology ; Panobinostat/pharmacology ; Apoptosis/drug effects ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Hydroxamic Acids/pharmacology ; MCF-7 Cells
مستخلص: Breast and ovarian cancers pose significant therapeutic challenges. We explored the synergistic cytotoxicity of histone deacetylase inhibitors (HDACis), poly(ADP-ribose) polymerase inhibitors (PARPis), and decitabine in breast (MDA-MB-231 and MCF-7) and ovarian (HEY-T30 and SKOV-3) cancer cell lines that were exposed to HDACi (panobinostat or vorinostat), PARPi (talazoparib or olaparib), decitabine, or their combinations. HDACi, PARPi, and decitabine combinations had synergistic cytotoxicity (assessed by MTT and clonogenic assays) in all cell lines (combination index < 1). Clonogenic assays confirmed the sensitivity of breast and ovarian cancer cell lines to the three-drug combinations (panobinostat, talazoparib, and decitabine; panobinostat, olaparib, and decitabine; vorinostat, talazoparib, and decitabine; vorinostat, olaparib, and decitabine). Cell proliferation was inhibited by 48-70%, and Annexin V positivity was 42-59% in all cell lines exposed to the three-drug combinations. Western blot analysis showed protein PARylation inhibition, caspase 3 and PARP1 cleavage, and c-MYC down-regulation. The three-drug combinations induced more DNA damage (increased phosphorylation of histone 2AX) than the individual drugs, impaired the DNA repair pathways, and altered the epigenetic regulation of gene expression. These results indicate that HDACi, PARPi, and decitabine combinations should be further explored in these tumor types. Further clinical validation is warranted to assess their safety and efficacy.
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معلومات مُعتمدة: CA016672 United States GF NIH HHS
فهرسة مساهمة: Keywords: DNA repair; HDAC inhibitors; PARP inhibitors; breast cancer; decitabine; ovarian cancer; synergistic cytotoxicity
المشرفين على المادة: 776B62CQ27 (Decitabine)
0 (Histone Deacetylase Inhibitors)
0 (Phthalazines)
0 (Poly(ADP-ribose) Polymerase Inhibitors)
WOH1JD9AR8 (olaparib)
0 (Piperazines)
58IFB293JI (Vorinostat)
9QHX048FRV (talazoparib)
9647FM7Y3Z (Panobinostat)
0 (Hydroxamic Acids)
تواريخ الأحداث: Date Created: 20240914 Date Completed: 20240914 Latest Revision: 20240924
رمز التحديث: 20240924
مُعرف محوري في PubMed: PMC11394699
DOI: 10.3390/ijms25179241
PMID: 39273190
قاعدة البيانات: MEDLINE
الوصف
تدمد:1422-0067
DOI:10.3390/ijms25179241