Survivin Down-regulation by α-Santalol Is Not Mediated Through PI3K-AKT Pathway in Human Breast Cancer Cells

Background: alpha-Santalol, a terpenoid found in sandalwood oil, has been shown to inhibit cancer cell growth in vitro by inducing apoptosis. This study was performed to investigate the anticancer properties of alpha-santalol associated with the induction of apoptosis in cultured MCF-7 [estrogen receptor (ER)-positive, and wild-type p53)] and MDA-MB231 (ER-negative and mutant p53) breast cancer cells. Materials and Methods: Expression of major proteins examined in the study were determined using a standard western blot protocol and analyzed by LICOR-Odyssey infrared scanner. Total protein levels of survivin were confirmed by survivin enzyme-linked immunosorbent assay (ELISA) kit. Cell viability was assessed by the trypan blue dye exclusion assay, and caspase-3 activity was determined by caspase-3 (active) ELISA kit. Results: Treatment of breast cancer cells for 6 and 9 h with alpha-santalol (20, and 40 mu M) resulted in statistically significant concentration-dependent down-regulation of survivin. Phosphorylated protein kinase B (pAKT) levels were found to be slightly up-regulated despite the down-regulation of survivin. Pharmacological inhibition of the phosphoinositide 3-kinase - protein kinase B (PI3K-AKT) pathway did not result in a synergistic/additive increase in cell death or caspase-3 activity caused by alpha-santalol. Conclusion: The study reveals that survivin down-regulation by alpha-santalol in breast cancer cells is not mediated through the PI3K-AKT pathway.