Brazilein inhibits survivin protein and mRNA expression and induces apoptosis in hepatocellular carcinoma HepG2 cells

Abstract

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.

Brazilein Increased Cytotoxic Activity of Doxorubicin on MCF-7/DOX Cells

“…It has already been reported that the cytotoxic effect of brazilein on Hep G2 cells occured via apoptosis induction and survivin protein expression suppression (Zhong, et al, 2009). …”

“…1) have cytotoxic effect on lung cancer cells, nasopharyngeal cancer cells, and prostate cancer cells with IC 50 value of 5-18 µM (Yen, et al, 2010). Brazilein inhibits survivin protein and induces apoptosis in HepG2 hepatocellular carcinoma cells (Zhong, et al, 2009). This study was conducted to evaluate the cytotoxic effect of brazilein, both alone and in combination with doxorubicin on MCF-7/DOX cells by using MTT assay.…”

Synergistic anticancer effects of curcumin and resveratrol in Hepa1-6 hepatocellular carcinoma cells

“…It has been reported that the inhibitors of apoptosis proteins, such as XIAP and survivin, are abnormally expressed in hepatocarcinoma cells and they have been confirmed as therapeutic targets for natural products (30)(31)(32). We further evaluated the effects of the combination treatment of curcumin and resveratrol on XIAP and survivin expression in Hepa1-6 cells.…”

Cytotoxic and Apoptotic-inducing Effect of Fraction Containing Brazilein from Caesalpinia sappan L. and Cisplatin on T47D Cell Lines

“…In addition, brazilin also increased the population of glioblastoma cells in cell cycle sub-G1 area (Lee, et al, 2013). While the other major compound of secang's heartwood, like brazilein, also known could increase the activation of caspase-9 and caspase-3, induce PARP cleavage and cause down-regulation of survivin protein on HepG2 liver cancer cells (Zhong, et al, 2009). On MCF-7 breast cancer cells, brazilein also could induce apoptosis through inhibition of survivin expression (Tao, et al, 2011).…”