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

Neumann, E.; Sohn, Y. S.; Karmi, O.; Darash Yahana, M.; Cardenas, A. E.; Pikarsky, E.; Elber, R.; Friedler, A.; Mittler, R.; Nechushtai, R.

doi:10.1101/2024.12.26.630413

bioRxiv · 10.1101/2024.12.26.630413

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

Neumann, E.·Sohn, Y. S.·Karmi, O.·Darash Yahana, M.·Cardenas, A. E.·Pikarsky, E.·Elber, R.·Friedler, A.·Mittler, R.·Nechushtai, R.

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Abstract

Ovarian cancer is the most fatal cancer of female reproductive organs. Ovarian cancer is typically diagnosed at a late stage, after metastasis occurred, leading to a 5-years relative survival rate of only [~]5%. Here, we demonstrate the anti-ovarian cancer properties of a peptide derived from the human protein CISD2/NAF-1 (3D-NAF-144-67-6K). This peptide selectively permeates the plasma membrane of ovarian cancer SKOV-3 cells without affecting healthy cells. 3D-NAF-144-67-6K targets and destroys the cancer cells mitochondria which leads to cancer cell death. In vivo studies of mice carrying xenograft tumours of SKOV-3 showed that the peptide significantly decreased the overall size and growth rate of both primary and metastatic ovarian cancer tumours. We further show that 3D-NAF-144-67-6K has a broad-spectrum anticancer activity targeting leukaemia, brain, and pancreas cancer cells. Our study suggests that 3D-NAF-144-67-6K could be used, alone or in drug combinations, to treat ovarian cancer and improve patient survival.

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Neumann, E., Sohn, Y. S., Karmi, O., Darash Yahana, M., Cardenas, A. E., Pikarsky, E., Elber, R., Friedler, A., Mittler, R., Nechushtai, R.. 2024-12-26. Targeting primary and metastatic ovarian cancer with a peptide derived from the human NAF-1/CISD2 protein. https://doi.org/10.1101/2024.12.26.630413

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