The art of traditional eastern medicine dates back thousands of years. It uses many unproven remedies, and many consider it a pseudo-science. However, modern research proves that there is indeed truth behind the tradition.
Celastrol is a compound found in the root of the thunder god vine. Traditional eastern medicine uses the root to treat cancer, kidney disease, and several other disorders. Studies have shown celastrol has anti-inflammatory, anti-obesity, and anti-cancer characteristics. The anti-cancer activities piqued the interest of a group from Beijing University, and they decided to investigate.
The group first began the investigation of celastrol after it came up in a screen for inhibitors of hepatocellular carcinoma metastasis. They found that celastrol could suppress cell migration, a key activity in metastatic cancers. A recent study predicted that celastrol could inhibit ROCK2 kinase based on structural models, so the team started from there.
The ROCK2 kinase connection revealed a possible mechanism by which celastrol could suppress metastasis of hepatocellular carcinomas. The team had previously studied a protein called ezrin. Ezrin acts as a cross-linker of the actin skeleton of a cell and the plasma membrane, and its active site is associated with the metastasis of hepatocellular carcinomas. ROCK2 is the kinase responsible for activating ezrin, and its inhibition by celastrol may prevent ezrin’s hyper-activation and the resulting pro-metastasis effects.
The team examined their hypothesis by in vitro experimentation. They used hepatocellular carcinoma cell lines to follow the formation of activated ezrin after the addition of celastrol. At the one-hour mark, they saw a fifty percent decrease in activated ezrin. The team observed a similar decline when they conducted the same experiment on ROCK2. Celastrol seemed to prevent the activation of ROCK2, which then prevented the activation of ezrin. One more test confirmed this connection, as celastrol elicited the same inhibition on cell migration as an ezrin mutant that prevented its activation by ROCK2.
Celastrol is a natural compound with a promising future in medicine. Several studies have already identified a link between celastrol and the prevention of cancer. This study reveals a possible mechanism by which celastrol prevents the activation of a ROCK2-ezrin signaling pathway, thereby suppressing metastatic activities in hepatocellular carcinomas. The team notes that celastrol is toxic to cells at high doses, preventing further experimentation.
The team concludes that celastrol has the potential for the clinical intervention of liver cancer metastasis and warrants further research. It also begs the question of what other new therapeutics will traditional medicine reveal. New studies are published every week, so we will soon find out.