title: Ferulic acid in combination with PARP inhibitor sensitizes breast cancer cells as chemotherapeutic strategy.
abstract: Homologous-recombination (HR)-dependent repair defective cells are hypersensitive to poly (ADP-ribose) polymerase (PARP) inhibitors. Combinations of defective HR pathway and PARP inhibitors have been an effective chemotherapeutic modality. We previously showed that knockdown of the WD40-repeat containing protein, Uaf1, causes an HR repair defect in mouse embryo fibroblast cells and therefore, increases sensitivity to PARP inhibitor, ABT-888. Similarly, here, we show that ferulic acid reduces HR repair, inhibits RAD 51 foci formation, and accumulates γ-H2AX in breast cancer cells. Moreover, ferulic acid, when combined with ABT-888, renders breast cancer cells become hypersensitive to ABT-888. Our study indicates that ferulic acid in combination with ABT-888 treatment may serve as an effective combination chemotherapeutic agent as a natural bioactive compound.
authors: Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
authors: Young Eun
authors: YE
authors: Choi
authors: Department of Food and Nutrition, School of Life Science and Nano-Technology, Hannam University, 461-6 Jeonmin-Dong, Yuseong-gu, Daejeon 305-811, Republic of Korea. Electronic address: eunmi_park@hnu.kr.
authors: Eunmi
authors: E
authors: Park
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D001940:Breast / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D003373:Coumaric Acids / Q000008:administration & dosage / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051135:Rad51 Recombinase / Q000378:metabolism; D059767:Recombinational DNA Repair / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D001562:Benzimidazoles; D003373:Coumaric Acids; D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C521013:veliparib; C004999:ferulic acid; D011065:Poly(ADP-ribose) Polymerases; D051135:Rad51 Recombinase
keywords: ABT-888; Breast cancer cells; Ferulic acid; Homologous-recombination repair