Prevention of Hepatocellular carcinoma progression by the Chinese herb derived peptide Lingzhi-8

Hepatocellular carcinoma (HCC) ranks sixth in incidence and third in mortality among all cancers worldwide. Metastatic spreads are responsible for poor prognosis of most HCC. The receptor tyrosine kinase of hepatocyte growth factor (HGF), c-Met, is now regarded as one of the promising therapeutic targets for prevention of HCC progression.   However, c-Met is positive in only 20% to 48% of human HCC cases. On the other hand, the side effects caused by conventional c-Met inhibitors were frequently observed. It is urgent to search more efficient antagonists with safety warrant for prevention of HCC progression.  One promising anti-HCC agent is the medicinal peptide LZ8 (also known as Lingzhi-8), which is purified from the Chinese herbal drug Ganoderma lucidium. Previously LZ8 has been found to acquire both immunomodulatory and anticancer capability. Recently, LZ8 was found to be an effective antagonist for prevention the progression of a lot of patient derived HCC cell lines both in vitro and in vivo. LZ8 may block c-Met-dependent or c-Met-independent signaling to achieve its anti-HCC effects. Deregulated endosomal signaling of c-Met is recently highlighted to be responsible for c-Met dependent tumor progression. Being a peptide with Lectin like activity, LZ8 may disturb c-Met endosomal processing by promoting the lysosomal degradation of c-Met, resulting in decreased c-Met signaling. In the future, LZ-8 may be proved as a more efficient and safe anti-HCC agent than the conventional drugs. Journal of Nature and Science, 1(3):e50, 2015.