Targeting primary and metastatic ovarian cancer with a peptide derived from the human NAF-1/CISD2 protein

Worldwide, female reproductive organ cancers account for more than 1.5 million new cases and 700,000 deaths each year. Of these, ovarian cancer (OC) is the most fatal. Regrettably, OC is typically diagnosed at a late stage, after metastasis occur, leading to a 5-year survival rate of only ∼30%. Current treatment options of advanced OC include chemotherapy combined with cytoreduction surgery, however, more than 80% of patients that responded to initial treatment experience relapse within 18 months. A dire need exists therefore for new therapy options that could replace, or be used in combination with, current therapies. Here, we report on the development of a peptide that selectively kills OC cells but is non-toxic to healthy cells in vitro and in vivo in a human OC xenograft mice system. The peptide (3D-NAF-1^44–67-6K) is derived from the human protein CISD2/NAF-1. It permeates the plasma membrane of OC cells, without affecting healthy cells, and targets their mitochondria leading to selective cancer cell death. In vivo studies using mice carrying xenograft tumours of human SKOV-3 cells showed that the peptide significantly reduces the overall size and growth rate of both primary and metastatic OC tumours. Our study suggests that 3D-NAF-1^44–67-6K could be used alone, or in combination with existing therapies, to treat OC and improve patient survival. We further show that 3D-NAF-1^44–67-6K has a broad-spectrum anticancer activity and can target brain and pancreatic cancer cells that are also unmet cancers with a high death rate.