Caspase Dependent and Independent Anti-hematological Malignancy Activity of AMHA1 Attenuated Newcastle Disease Virus.

Abstract

Hematological malignancies remain one of the leading causes of death worldwide despite advances in cancer therapeutics. Newcastle disease virus (NDV) is a member of Paramyxoviridae that elicits considerable interest as an anticancer agent because it can replicate up to 10 000 times faster in human cancer cells than in most normal cancer cells. Several NDV strains reportedly induce the cytolysis of cancerous cell lines. The attenuated Iraqi strain (AMHA1) of NDV is a novel oncolytic agent with promising antitumor characteristics, including apoptosis induction. This study aimed to evaluate the ability of the AMHA1 NDV strain to induce apoptotic cell death in hematological tumors through caspase-dependent or independent apoptotic pathways. The cytolytic effects of AMHA1 NDV strains of different multiplicity of infection (MOIs) (20, 15,10, 5, 3, 1, 0.5, and 0.1 )and exposure for all hematological malignancy cell lines (human non-Hodgkin lymphoma SR and human multiple myeloma (COLO 677) and human monocytic leukemia THP1) have been determined through a microtetrazolium (MTT) assay. Propidium iodide and acridine orange (AO/PI) double staining were used to examine the ability of attenuated NDV strain to induce apoptosis in infected cells under a fluorescence microscope and to quantify the percentage of apoptosis induction. Quantitative immunocytochemistry assay was further used to study the caspase-dependent and independent protein expression levels in infected and control cells. Cells treated with NDV strains showed a higher cell-death percentage than untreated cells as quantified by the MTT assay. AO/PI results revealed that NDV exerted a powerful and significant effect on apoptosis induction (P<0.0001) in the human cancer cell lines tested in comparison with control cells. Immunocytochemistry in AMHA1 NDV- infected human hematological cell lines revealed a remarkable increase in the expression of caspase 8, 9 (dependent pathway), apoptosis-inducing factor, and endonuclease G (independent pathway) in comparison with untreated cells. This study demonstrated the role of the Iraqi NDV strain in inducing apoptosis through dependent and independent pathways in cancer cells and thus its high potential as an antitumor agent.