Oncolytic Iraqi NDV induce apoptosis

What is it about?

Newcastle disease virus is very promising antitumor agent. Iraqi virulent strain showed pronounced oncolytic activity. This study aimed to investigate the specific pathway of apoptosis induced by Iraqi strain of Newcastle disease virus (NDV) on tumor cells In vitro and In vivo. Several cell lines were tested (Human rhabdomyosarcoma cell line (RD), Human Glioblastoma multiforme culture (AMGM) and Murine mammary adenocarcinoma cell line ( AMN3) for ability of Iraqi NDV strain to induce apoptosis and to give deep look about the main pathway that induce apoptosis in tumor cell lines by the virus. The cell lines were infected with Newcastle disease virus and investigated for apoptotic pathway by using immunocytochemistry for caspase 3, 8, and 9. The result of this in vitro experiment revealed that NDV induce apoptosis in tumor cell lines when compared to control group with marked increase in the percentage of cells expressing caspase 9 with low percentage of cells expressing caspase 8 in NDV treated group at 24,48hr. These results indicated the role of NDV Iraqi strain in inducing apoptosis through intrinsic mitochondrial pathway in vitro. The in vivo experiment included female mice transplanted with mammary adenocarcinoma transplantable tumor line (AM3), after tumor growth; tumor bearing mice randomly divided into groups, first group treated by NDV by intratumoral injection, second group treated by NDV intrapretonially. Caspase 3, caspase 8, and caspase 9 expression in tumor sections were checked after 24hrs, 48hrs, 72hrs, 7 and 14 days of treatment with NDV. The results revealed that NDV induce apoptosis significantly in treated tumors by both ways IT and IP when compared with control group. There is significant (p<0.05) marked increase in the mean percentage of cells expressing caspase 9 in NDV treated groups compared with mean percentage of cells expressing caspase 8 and untreated control group at 24,48,72,1week, 2 weeks post single injection treatment. Moreover, Caspase-8 expression in IT and IP groups was significantly higher than control untreated group. These results revealed that NDV had a powerful effect on inducing mitochondrial (intrinsic) apoptotic pathway in vivo in association of extrinsic pathway. This association can explained by NDV induction for antitumor immune response and this immune response can trigger tumor killing by extrinsic pathway. The current work suggest that Iraqi oncolytic virulent strain of NDV induce apoptosis through intrinsic pathway directly as the results of in vitro study and induce extrinsic pathway indirectly through immune stimulation properties of NDV.

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Why is it important?

it describe the mechanism of apoptosis induction of oncolytic NDV Iraqi strain in vitro and in vivo