Oncolytic Newcastle disease virus reduces growth of cervical cancer cell by inducing apoptosis

Abstract

Although Oncolytic viruses have been regarded as a promising tool for targeted therapy of cancer, accomplishing high efficacy and specificity with this strategy is challenging. Oncolytic virotherapy is one of the novel therapeutic methods recently used for the therapy of human malignancies. Cervical cancer is on the major public health problem and the second most common cause of cancer death among females in less developed countries. The aim of this study was mainly to determine the apoptosis effect of oncolytic Newcastle disease virus (NDV) in TC-1 cell line.In the current study, the oncolytic NDV, vaccine strain LaSota, was used to infect murine TC-1 cells of human papillomavirus (HPV)-associated carcinoma which expressing human papillomavirus 16 (HPV-16) E6/E7 antigens in vitro. The effectiveness of NDV for cervical cancer cell line was investigated by evaluating the antitumor activity of oncolytic NDV and the involved mechanisms. Antitumor activities of oncolytic NDV were assessed by cell proliferation (MTT) and lactate dehydrogenase (LDH) release analysis. In addition, molecular changes of early stage of apoptosis and the role of reactive oxygen species (ROS) were analyzed by flow cytometry and Western Blot in NDV-treated TC-1 cells.The results showed that NDV treatment significantly decreased the viability of a TC-1 cell line and suppressed the growth by inducing apoptotic cell death. In addition, we demonstrated that NDV-induced apoptosis of TC-1 cells is mediated by ROS production. In summary, our findings suggest that oncolytic NDV is a possible therapeutic candidate as a selective antitumor agent for the treatment of cervical cancer.

Virotheranostics, a double-barreled viral gun pointed toward cancer; ready to shoot?

“…Consequently, finding novel methods for increasing the efficiency of tumor imaging and treatment is of great importance [1,2]. Recently, oncolytic virotherapy has provided a new outlook for the therapy of malignancies with promising outcomes [3,4]. Oncolytic viruses (OVs) specifically induce cancer cells death by infection of and spreading on tumor cells through different mechanisms such as direct lysis effect or adjacent cells fusion.…”

Synergy between hemagglutinin 2 (HA2) subunit of influenza fusogenic membrane glycoprotein and oncolytic Newcastle disease virus suppressed tumor growth and further enhanced by Immune checkpoint PD-1 blockade

“…However, statistics about the incidence of many thousands of newfangled cases diagnosed with cervical cancer and the huge number of deaths among previously diagnosed patients in 2018 clarify the inefficiency of present cervical cancer prevention and treatment methods [2]. To address the shortcomings of present therapeutic methods and along with advancements in synthetic biology, immunotherapy and oncolytic virotherapy have emerged as alternative or complementary cervical cancer treatments [3]. Regarding immunotherapy techniques, the employment of HPV vaccines, adoptive T-cell therapy, and immune checkpoint blockade have investigated [4,5].…”

“…However, the effectiveness of monotherapy with immune checkpoint blockade in clinical trials is doubtful and in some cases, the results are not satisfactory enough [8]. Besides these dissatisfactory approaches, oncolytic virotherapy with distinctive characteristics has shown promising results against cervical cancer [3]. Direct oncolysis along with the provocation of host systemic innate and adoptive immune responses introduce oncolytic virotherapy as one of the treatment methods with the most optimistic results in the treatment of human cancers [9].…”

Oncolytic Newcastle disease virus delivered by Mesenchymal stem cells-engineered system enhances the therapeutic effects altering tumor microenvironment

“…In vivo tracking of the MSCs migratory ability in the tumor microenvironment is essential for the application of stem cells for cancer immunotherapy. [26]. In addition to direct antitumor effect, oncolytic virotherapy also exerts a robust danger signal needed for overcoming tumor-induced immune suppression and subsequent stimulation of potent antitumor immunity in vivo [33].…”

“…Our previous studies have shown that oncolytic NDV induces apoptosis in TC-1 cell line [26]. In addition, Kumar et al found that NDV mediates tumor cell killing through promoting the TNF-related apoptosis-inducing ligand (TRAIL)/TRAIL-R signaling, caspases activation, as well as apoptosis in the extrinsic pathway in HeLa cells [25].…”