Curcumin enhances poly(ADP-ribose) polymerase inhibitor sensitivity to chemotherapy in breast cancer cells.
Poly(ADP-ribose) polymerase (PARP) inhibitor has shown promising responses in homologous recombination (HR) repair-deficient cancer cells. More specifically, targeting HR pathway in combination with PARP inhibitor has been an effective chemotherapy strategy by so far. Curcumin has been recognized as anticancer agents for several types of cancers. Here, we demonstrate that curcumin inhibits a critical step in HR pathway, Rad51 foci formation, and accumulates γ-H2AX levels in MDA-MB-231 breast cancer cells. Curcumin also directly reduces HR and induces cell death with cotreatment of PARP inhibitor in MDA-MB-231 breast cancer cells. Moreover, curcumin, when combined with ABT-888, could effectively delayed breast tumor formation in vivo. Our study indicates that cotreatment of curcumin and PARP inhibitor might be useful for the combination chemotherapy for aggressive breast cancer treatment as a natural bioactive compound.
Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
Young Eun
YE
Choi
Department of Food and Nutrition, School of Life Science and Nano-Technology, Hannam University, Daejeon 305-811, Korea. Electronic address: eunmi_park@hnu.kr.
Eunmi
E
Park
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001562:Benzimidazoles / Q000737:chemistry; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D003474:Curcumin / Q000737:chemistry* / Q000494:pharmacology; D004260:DNA Repair / Q000187:drug effects; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000737:chemistry*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051135:Rad51 Recombinase / Q000378:metabolism; D011995:Recombination, Genetic
D000970:Antineoplastic Agents; D001562:Benzimidazoles; C468783:H2AX protein, human; D006657:Histones; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C521013:veliparib; D049452:Green Fluorescent Proteins; D011065:Poly(ADP-ribose) Polymerases; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; D003474:Curcumin
Breast cancer cells; Chemotherapy; Curcumin; Homologous-recombination repair; PARP inhibitor