Seaweed Laminaria japonica peptides possess strong anti-liver cancer effects

Background: Seaweed Laminaria japonica is widely consumed worldwide. This seaweed has also been used in traditional Chinese medicine for hundreds of years. Recent studies have shown that Laminaria japonica has multiple beneficial effects for human health, however, little is known about its anti-tumour effects. In the current study, we extracted Laminaria japonica peptides (LJPs) using an activity tracking method and explored the anti-tumour (liver cancer) activity of the peptides both in vivo and in vitro. Methods: The LJP’s were isolated with fresh Laminaria japonica and purified by Reversed Phase-High Performance Liquid Chromatography and HPLC-ESI-MS. Liver cancer cell lines HuH7, HepG2 cells and the human liver cell line HL-7702 cells were used throughout the experiment. The HepG2 cells were treated with LJP-1 (0, 0.36 mM and 1.80 mM) for 24 h, and cell apoptosis and cell cycle were evaluated. MTT assay was used to examine the cytotoxicity activity of the LJPs. Pro-apoptotic factors (including. Bax, Bid) and anti-apoptotic factors (including, Bcl-2, Bcl-xL) were investigated in cells treated with LJP. Caspase activation was examined by detecting the protein expressions of Caspase 3, Caspase 9, Cleaved caspase 3, Cleaved caspase 9 and Cleaved PARP using western blot. The phosphatidylinositol-3-kinase (PI3K)/AKT pathway and the phosphorylation states of the MAPKs (p38 and JNK) were also examined. The in vivo anti-liver cancer effect of LJP was investigated using a mouse model. Results: Results showed that LJP-1 [EGFHL] performed the most anti-proliferative activity in H22 cells in vitro. LJP-1 blocked the H22 cells in G0/G1 phase accompanied by inhibition of cyclins expression. Further experiments revealed that LJP-1 induced H22 cell apoptosis via Caspase activation and ASK1/MAPKs pathway regulation. At the same time, LJP-1 significantly inhibited the tumour growth and induced tumour cell apoptosis and necrosis in vivo. Conclusions: Our results support that the peptides (LJP’s) from Laminaria japonica possess strong inhibitory effects on the growth of liver cancer both in vivo and in vitro. LJP-1 induces HCC cell apoptosis through the Caspase-dependent pathway and via G0/G1 phase arrest by regulating cell cycle checkpoint proteins. Additionally, LJP-1 induces Caspase dependent apoptosis, in part by inhibiting the PI3K/AKT and MAPK signaling pathways. Potentially LJP-1 could be a novel candidate for human liver cancer therapeutics