<p>Fucoidan Induces Apoptosis and Inhibits Proliferation of Hepatocellular Carcinoma via the p38 MAPK/ERK and PI3K/Akt Signal Pathways</p>

Abstract

Purpose: Fucoidan is a natural bioactive product with broad therapeutic applications. Hepatocellular carcinoma (HCC) is a common malignancy of the liver associated with a relatively high mortality rate; thus, effective treatments are urgently needed. Here, the effects of fucoidan on HCC and the underlying mechanism were explored. Methods: The proliferation and apoptosis of two HCC cell lines (BEL-7402 and LM3) treated with different concentrations of fucoidan or saline were assessed. The levels of proliferating cell nuclear antigen (PCNA) and CCK8 assay were used to determine proliferative capabilities of BEL-7402 and LM3 cells. Apoptosis of LM3 cells was assessed by Hoechst 33342 staining, Western blotting and flow cytometry. The capability of fucoidan to inhibit the growth of LM3 cells was investigated by monitoring of the p38 MAPK/ERK pathways and the upstream kinases, PI3K/Akt. LM3 xenograft tumors were used for in vivo verification. Results: Cell proliferation and apoptosis assays consistently showed that fucoidan has an inhibitory effect on cell growth. Fucoidan significantly promoted apoptosis of LM3 cells through a mechanism involving activation of caspases 8, 9, and 3 accompanied by changes in B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax), as well as changes in the phosphorylation of p38 MAPK and ERK. Fucoidan also altered the phosphorylation of its upstream kinase, Akt. Fucoidan treatment markedly reduced the growth of LM3 xenograft tumors, consistent with the in vitro results. Conclusion: Fucoidan conveys antitumor effects and, thus, should be further explored as a potential treatment option for HCC.

The Therapeutic Potential of the Anticancer Activity of Fucoidan: Current Advances and Hurdles

“…Duan et al showed that fucoidan plays a significant role in inhibiting cell proliferation in BEL-7402 and LM3 cell lines through the p38MAPK/ERK pathway [ 82 ]. Fucoidan administration results in the upregulation of NDRG-1/CAP43, mediated by the inhibition of hepatocarcinoma cells.…”

Fucoidan from Laminaria japonica Inhibits Expression of GLUT9 and URAT1 via PI3K/Akt, JNK and NF-κB Pathways in Uric Acid-Exposed HK-2 Cells

“…It is revealed that FPS may reduce UA damage to HK-2 cells via the JNK signaling pathway. Many studies have shown that FPS plays an anti-cancer role through the MAPK pathway [ 26 , 27 ].…”

Critical signaling pathways governing hepatocellular carcinoma behavior; small molecule-based approaches

“…In HCC late stages, autophagy promotes survival, metastasis, and EMT via activation of the TGFβ pathway, P53 degradation, and chemotherapy resistance of HCC [ 167 ]. Inhibitors of main signaling pathways such as PI3K/Akt, MAPK/ERK, and JAK/Stat3 can induce autophagy and cell death in HCC [ 168 , 169 ]. Small molecules like rapamycin, Mitoxantrone (PI3K/mTOR inhibitors), and Erlotinib/Cetuximab (EGFR inhibitors) are thought to activate cellular autophagy and apoptosis in various HCC cell lines [ 167 , 170 ].…”