br cytochrome C release and intrinsic pathway
cytochrome C release and intrinsic pathway activation, it also combined with Bcl-2 family proteins, resulting in activation of mitochondrial dysfunction, and then leading to caspase activation and cell death (Nakano et al., 2001). The induction of bax and bcl-2 was inhibited in buforin IIb treated 丝裂霉素C by P53 knockdown, suggesting that buforin IIb induced apoptosis in cells (Fig. 4A). In addition, the anti-cancer eﬀect of buforin IIb was repressed by the p53 knockdown, which inhibited PARP cleavage (Fig. 4B). Taken together, buforin IIb induces apoptosis through the modulation of caspase pathway and p53-Bcl-2 family proteins. In conclusion, our results showed buforin IIb exerted an in-hibitory eﬀect on PC-3 and Du-145 cells, induced AIPC cell apoptosis through increasing the mRNA level of p53 gene and its target genes and modulating the protein level of p53–Bcl-2 family protein. Our study suggested that buforin IIb could be a promising candidate for ther-apeutic treatment for prostate cancer therapy.
This work was supported by the China Postdoctoral Science Foundation (grant numbers 2018M643676) and Shaanxi Province Postdoctoral Science Foundation.
Conflicts of interest
The authors declared that there is no conflict of interest.
JS Z and YY H conceived and designed the experiments. YY H and M L Performed the experiments. JS Z, YY H and M L Analyzed the data and Wrote the manuscript. All authors read and approved the final manu-script.
Appendix A. Supplementary data
2008. Mechanism of anticancer activity of buforin IIb, a histone H2A-derived peptide.
Contents lists available at ScienceDirect
journal homepage: www.elsevier.com/locate/lifescie
Bufothionine exerts anti-cancer activities in gastric cancer through Pim3 T
Guojun Wang , Guanghui Liu, Yanwei Ye, Yang Fu, Xiefu Zhang
The Department of Gastrointestinal surgery, The First Aﬃliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China
Aim: Gastric cancer (GC) is the fourth most common cancer globally. Bufothionine is a major active constituent of Cinobufacini (Huachansu), which is extracted from the skin and parotid venom gland of the toad Bufo bufo gargarizans Cantor. It exhibits anti-cancer activities in vitro. However, whether bufothionine exerts anti-cancer activities against GC is unknown. This study was designed to evaluate the eﬃcacy of bufothionine in vitro and in vivo.
Material and methods: MKN28 and AGS cells were chosen as cell models to study the anti-cancer eﬀect of bu-fothionine. Cell viability was determined by CCK-8 assay, while the eﬀect of bufothionine on cell membrane integrity was examined by LDH assay. Cell apoptosis was detected by Hoechst/PI staining and Annexin V-FITC/ PI staining followed by flow cytometry analysis. The expression levels of proteins involved were examined using western blotting. I-Traq analysis was conducted to identify the diﬀerentially expressed genes in AGS cells fol-lowing bufothionine treatment. The anti-growth eﬀect of bufothionine was validated in vivo using a GC xenograft model.
Key findings: The results revealed that bufothionine prevented the growth, destroyed cell membrane and pro-moted apoptotic cell death of GC cells. iTRAQ analysis revealed thatPIM3 might be a molecular target re-sponsible for the anti-cancer eﬀects of bufothionine. It was also found that PIM3 knockdown significantly augmented the anti-growth and pro-apoptotic eﬀects of bufothionine in GC cells. In contrast, ectopic PIM3 expression markedly dampened the anti-neoplastic activities of bufothionine. The expression of PIM3 was also suppressed by bufothionine treatment in xenograft tumor tissue.
Significance: Bufothionine exhibited anti-cancer activities in vitro and in vivo in GC via downregulating PIM3.
Gastric cancer (GC) is the fourth most common cancer globally and the third leading cause of cancer-related deaths . In China, the in-cidence of GC is high . Currently, surgery is the mainstream ther-apeutic regimen for GC. Recently, a variety of chemotherapeutic agents have been introduced for the treatment of GC. However, the prognosis of GC patients remains far from being satisfactory going by the poor 5-year survival rate, which is attributed to late diagnosis and chemo-re-sistance . Hence, it is imperative to investigate novel treatment agents for GC.
PIM3 is a member of the Provirus integrating site Moloney murine leukemia virus (Pim) family, which belongs to the Ca2+/calmodulin-dependent protein kinase (CaMK) group and exhibits serine/threonine kinase activity [4,5]. It has been evidenced that Pim3 is involved in various human malignances . PIM-3 displays aberrant high expres-sion in a variety of endoderm-derived tumors such as adenocarcinoma, hepatocellular carcinoma, and pancreatic cancer. However, the