AUTHOR=Al-Shammari Ahmed Majeed , Salman Marwa Ibrahim TITLE=Antimetastatic and antitumor activities of oncolytic NDV AMHA1 in a 3D culture model of breast cancer JOURNAL=Frontiers in Molecular Biosciences VOLUME=Volume 11 - 2024 YEAR=2024 URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2024.1331369 DOI=10.3389/fmolb.2024.1331369 ISSN=2296-889X ABSTRACT=Newcastle disease virus (NDV) AMHA1 is capable of killing cancer cells by direct replication or by induction of apoptosis alongside other pathways. Here, we report the potent antimetastatic and anticancer activities of NDV AMHA1 in a 3D spheroids model of breast cancer metastasis. We used two breast cancer cell lines AMJ13 and MCF7 in our metastasis model system. First, we showed that NDV AMHA1 can infect and kill breast cancer cells in proliferating adherent cells and tumor spheroids using different virus doses and studying virus replication kinetics. It showed that NDV can infect and spread within the spheroids that represent metastasis before and after reattachment. Furthermore, we evaluated the ability to induce apoptosis in cancer spheroids and, by virus tracking, showed that NDV infection is essential for the elimination of these metastasis spheroids. The mechanism by which NDV induces cell killing in the metastasis model is by induction of caspase-3 and P21 and inhibiting Ki67 in cancer cells but not in normal cells. In conclusion, these results indicate that NDV AMHA1 has the ability to kill breast cancer metastases in suspension or attached and this is a novel finding of being NDV AMHA1 is a possibly efficient therapy against human metastatic breast cancer.