Hepatocellular carcinomas represent the third leading cause of
cancer-related deaths worldwide.
Survivin, a structurally unique member of the
inhibitor of apoptosis protein (IAP) family, is overexpressed in a wide range of
malignancies, including
hepatocellular carcinoma. Due to its involvement in
cancer progression and treatment resistance,
survivin is currently undergoing extensive investigation as a novel intervention target to induce apoptosis in
cancer cells by
phytochemicals or synthetic agents.
Brazilein, a compound obtained in a large amount from the dried heartwood of Caesalpinia sappan Linn., which has long been used in
traditional medicine in China, has some pharmacological activities. Human
hepatocellular carcinoma HepG2 cells were treated with
brazilein and analyzed for
survivin protein and
mRNA levels by Western blotting and real-time RT-PCR, respectively.
Brazilein treatment of cells for 48 h at 5 and 10 microg/ml doses resulted in significantly decrease in
survivin protein expression. We also observed that
brazilein caused a strong decrease in
survivin mRNA expression. In other studies, down-regulation of
survivin by
brazilein was associated with a strong and prominent caspases-9 and -3 activation as well as PARP cleavage. It was also shown that
brazilein induced a strong apoptotic cell death, as shown by
DNA ladder assay, and growth inhibition of HepG2 cells. Further studies are needed to investigate in vivo effect of
brazilein on
survivin expression and associated
biological effects in
hepatocellular carcinoma that could provide useful information for
brazilein efficacy in the prevention/intervention of human
hepatocellular carcinoma.