ABSTRACT
New therapeutic approaches can significantly impact the control of colorectal cancer (CRC), which is increasing worldwide. In this study, we investigated the potential of targeting viral proteins to combat cancer cells. Specifically, we examined the anticancer potential of the matrix (M) protein of the mumps virus Hoshino strain in SW480 CRC cell lines. To begin, we individually transfected SW480 cells with pcDNA3 plasmids containing the mumps virus M gene. We then investigated the percentage of cell death, caspase activity, and the expression levels of genes involved in apoptosis pathways. Following this, we performed bioinformatics analysis on the M protein to identify any similarities with Bcl-2 family members and their viral homologs. Our diagnostic methods showed that treatment with the mumps M protein induced apoptosis and upregulated the expression and activity of pro-apoptotic proteins in SW480 CRC cells compared to the control and vector groups. Based on our bioinformatics studies, we proposed that the BH3 motif in the M protein may trigger apoptosis in CRC cells by interacting with cellular Bax. Overall, our study showed for the first time that the mumps virus M protein could be considered as a targeted treatment for CRC by inducing apoptotic pathways.
Subject(s)
Colorectal Neoplasms , Mumps virus , Humans , Mumps virus/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Cell Line, Tumor , Proto-Oncogene Proteins c-bcl-2 , Apoptosis/geneticsABSTRACT
Colorectal cancer (CRC) is a common and highly malignant neoplasm, ranking as the fourth most frequent cause of cancer-related deaths worldwide. Recently, non-human oncolytic viruses such as Peste des petits ruminants virus (PPRV) are considered as a potent candidate in the viral therapy of cancer. In the current study, the apoptotic effects of matrix (M) protein of PPRV was investigated on SW480 CRC cells. The M gene was cloned into the pcDNA™3.1/Hygro(+) expression vector and transfected into the cancer cells. The cytotoxic effects of the M protein on SW480 cells were confirmed using MTT assay. Furthermore, flow cytometry results showed that the M protein induces apoptosis in 91 % of CRC cells. Interestingly, the expression of the M gene in SW480 cells led to the up-regulation of genes including Bax, p53, and Caspase-9, as well as an increase in the Bax/Bcl-2 ratio. By using bioinformatics modeling, we hypothesized that the M protein could interact with Bax factor through its BH3-like motif and could further activate the intrinsic apoptosis pathway. Ultimately, this study provided the first evidence of the pro-apoptotic activity of PPRV M protein indicating its possible development as a promising novel anti-cancer agent.
Subject(s)
Colorectal Neoplasms , Peste-des-Petits-Ruminants , Peste-des-petits-ruminants virus , Animals , Humans , Peste-des-petits-ruminants virus/genetics , bcl-2-Associated X Protein/genetics , Apoptosis , GoatsABSTRACT
A novel bio-nanocomposite was prepared by the combination of fungal biomass and Fe3O4 magnetic nanoparticles. The result of XRD and EDAX analysis indicated that Fe3O4 Actinomucor sp. bio-nanoadsorbent was prepared. Our experiments showed that the adsorption kinetics and isotherm of this material comply with the pseudo-second-order and the Langmuir models, respectively. The maximum adsorption capacity (qmax) of this novel bio-nanoadsorbent was obtained as 29.49 mg/g. The thermodynamic analysis revealed that the adsorption of Cd2+ is spontaneous and exothermic. The optimum temperature, initial concentration, contact time and pH for adsorption system of cadmium were about 45 °C, 400 mg/L, 120 min and 7, respectively. Pretreatment of adsorbent by NaOH and SDS significantly increased cadmium adsorption capacity. SEM images showed that Fe3O4 nanoparticles were immobilized successfully on the fungus cell surface. Contribution of the carboxyl, hydroxyl, amine and Fe-O functional groups of the bio-nanoadsorbent in the binding to cadmium ions was revealed by FTIR analysis. Results from regeneration studies indicated reusability of the adsorbent up to 91%. According to experimental results, it could be claimed that bio-nanocomposite of Fe3O4-Actinomucor sp. is a novel efficient adsorbent for removal of metal ions from aqueous solutions, and hence it has potential to be used in the environmental pollution cleanup programs.