Sigma-2 ligands and PARP inhibitors synergistically trigger cell death in breast cancer cells

Elizabeth S. McDonald, Julia Mankoff, Mehran Makvandi, Wenhua Chu, Yunxiang Chu, Robert H. Mach, Chenbo Zeng

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


The sigma-2 receptor is overexpressed in proliferating cells compared to quiescent cells and has been used as a target for imaging solid tumors by positron emission tomography. Recent work has suggested that the sigma-2 receptor may also be an effective therapeutic target for cancer therapy. Poly (ADP-ribose) polymerase (PARP) is a family of enzymes involved in DNA damage response. In this study, we looked for potential synergy of cytotoxicity between PARP inhibitors and sigma-2 receptor ligands in breast cancer cell lines. We showed that the PARP inhibitor, YUN3-6, sensitized mouse breast cancer cell line, EMT6, to sigma-2 receptor ligand (SV119, WC-26, and RHM-138) induced cell death determined by cell viability assay and colony forming assay. The PARP inhibitor, olaparib, sensitized tumor cells to a different sigma-2 receptor ligand SW43-induced apoptosis and cell death in human triple negative cell line, MDA-MB-231. Olaparib inhibited PARP activity and cell proliferation, and arrested cells in G2/M phase of the cell cycle in MDA-MB-231 cells. Subsequently cells became sensitized to SW43 induced cell death. In conclusion, the combination of sigma-2 receptor ligands and PARP inhibitors appears to hold promise for synergistically triggering cell death in certain types of breast cancer cells and merits further investigation.

Original languageEnglish
Pages (from-to)788-795
Number of pages8
JournalBiochemical and Biophysical Research Communications
Issue number3
StatePublished - May 6 2017


  • Breast cancer
  • PARP inhibitor
  • Sigma-2 receptor
  • Synergy
  • Synthetic lethal
  • Therapeutics


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