Objective:The morbidity of malignant melanoma keeps increasing annually.It has high risks of metastasis,drug resistance,and poor prognosis in clinics.Moreover,the available medicines used commonly,such as dacarbazine,temozolomide,the v-Raf murine sarcoma viral oncogene homolog B1(BRAF) inhibitor vemurafenib,and the programmed cell death protein 1 inhibitor pembrolizumab,have some limitations at some extent.Therefore,a more effective therapeutic strategy is still urgently necessary.Methods:In this study,Brucea javanica(L.)Merr.globulins were hydrolyzed with pepsin,then ultra-filtrated to collect small molecular peptides (≤3 kDa).The peptides were then analyzed by anti-proliferative assay,cell-cycle distribution,apoptosis assay,and in vitro wound-scratch assay.Finally,western blotting was conducted to elucidate the underlying anti-melanoma mechanism.Results:The small molecular peptide from B.javanica significantly inhibited malignant melanoma cell proliferation with the IC50 of 2.72 μg/mL for 72 h.Further analysis indicated that B.javanica peptides arrested cell cycle at the S and G2/M phases and induced apoptosis by upregulating p21,p53,Bax,caspase-3,and cleaved PARP while downregulating Bcl-2 expression.The inhibitory migration effects were also confirmed by wound-healing assay.Conclusion:The small molecular biopeptides from B.javanica may be a promising bioactive agent candidate for melanoma treatment.

Yi Zhao;Huiyun Wang;Yanyan Yin;Haoyu Shi;Dong Wang;Fengjue Shu;Rongchun Wang;Lingzhi Wang

School of Life Sciences,Beijing University of Chinese Medicine,Beijing,102488,China;School of Traditional Chinese Medicine,Beijing University of Chinese Medicine,Beijing,102488,China;Karna Limited Liability Company,Atlanta,30345,USA;Biology Institute,Qilu University of Technology (Shandong Academy of Sciences),Jinan,250103,China

中医科学杂志（英文）

[1]Yi Zhao;Huiyun Wang;Yanyan Yin;Haoyu Shi;Dong Wang;Fengjue Shu;Rongchun Wang;Lingzhi Wang-.Anti-melanoma action of small molecular peptides derived from Brucea javanica (L.) Merr.globulin in vitro)[J].中医科学杂志（英文）,2022(01):85-91

dacarbazine,globulins,filtrated,biopeptides

Anti,melanoma,action,small,molecular,derived,from,Brucea,javanica,Merr,vitro,Objective,morbidity,malignant,keeps,increasing,annually,It,high,risks,metastasis,drug,resistance,poor,prognosis,clinics,Moreover,available,medicines,used,commonly,such,temozolomide,Raf,murine,sarcoma,viral,oncogene,homolog,B1,BRAF,vemurafenib,programmed,cell,death,protein,pembrolizumab,have,some,limitations,extent,Therefore,more,effective,therapeutic,strategy,still,urgently,necessary,Methods,In,this,study,were,hydrolyzed,pepsin,then,ultra,collect,kDa,analyzed,by,anti,proliferative,assay,cycle,distribution,apoptosis,wound,scratch,Finally,western,blotting,was,conducted,elucidate,underlying,mechanism,Results,significantly,inhibited,proliferation,IC50,Further,analysis,indicated,that,arrested,G2,phases,induced,upregulating,p21,p53,Bax,caspase,cleaved,PARP,while,downregulating,Bcl,expression,inhibitory,migration,effects,also,confirmed,healing,Conclusion,may,be,promising,bioactive,agent,candidate,treatment

0.643908