Induction of apoptosis in colorectal cancer cells by matrix protein of PPR virus as a novel anti-cancer agent

被引:5
作者
Masoudi, Ramin [1 ]
Mohammadi, Ali [2 ,4 ]
Morovati, Solmaz [1 ]
Heidari, Amir Ali [3 ]
Asad-Sangabi, Mehdi [2 ]
机构
[1] Shiraz Univ, Sch Vet Med, Dept Pathobiol, Div Biotechnol, Shiraz, Iran
[2] Shiraz Univ, Sch Vet Med, Dept Pathobiol, Div Virol, Shiraz, Iran
[3] Shiraz Univ, Sch Vet Med, Dept Clin Sci, Div Aquat Anim Hlth & Dis, Shiraz, Iran
[4] Shiraz Univ, Sch Vet Med, Dept Pathobiol, Div Virol, Shiraz 7144111731, Fars, Iran
关键词
Anti-cancer; BH3-like motif; Intrinsic apoptosis; M protein; PPRV; SW480; cells; PETITS RUMINANTS VIRUS; BLOCKS APOPTOSIS; CORE PROTEIN; MYXOMA VIRUS; IN-VITRO; BCL-2; INHIBITION; BAX/BCL-2; THERAPY; M11L;
D O I
10.1016/j.ijbiomac.2023.125536
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 pcDNATM3.1/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.
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收藏
页数:7
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