Anti-melanoma action of small molecular peptides derived from Brucea javanica (L.) Merr. globulin in vitro

Abstract

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. 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. The small molecular peptide from B. javanica significantly inhibited malignant melanoma cell proliferation with the IC 50 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. The small molecular biopeptides from B. javanica may be a promising bioactive agent candidate for melanoma treatment.