Abstract
Hepatocellular carcinoma (HCC) is the primary liver cancer that occurs with a high incidence in Asia. Owing to the poor prognosis of the disease, the mortality rate remains high, making HCC the third most common cause of cancer-related mortality worldwide. Studies on current therapies have generated little empirical evidence in improving the survival rate of patients with advanced HCC. Certain agents have exhibited promising results in molecular targeted therapy, but they remain in clinical trials. Aconitine, a main bioactive constituent of a traditional Chinese herb, Wutou, and belonging to the Aconitum genus, has been demonstrated to inhibit the growth of certain tumors, including HCC, but the underlying molecular mechanism by which aconitine inhibits tumor growth is largely unknown. In the present study, aconitine was applied to two types of hepatic carcinoma cells and normal hepatic cells at various concentrations, and it was found to specifically inhibit the proliferation of cancer cells in a dose-dependent manner. Further study found that aconitine activated the production of reactive oxygen species, leading to an increased release of cytochrome c from mitochondria and the activation of apoptosis. This is demonstrated by the increased cleavage of caspases 3 and 7, as well as an increased B-cell lymphoma 2 (Bcl-2)-associated X protein level and a decreased Bcl-2 level in cancer cells. An in vivo study also found that aconitine was able to inhibit the growth of tumors in mice. The results of the present study suggest that aconitine has the potential to be developed into an effective anti-HCC agent.