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

Abstract

BACKGROUND:

α-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 α-santalol associated with the induction of apoptosis in cultured MCF-7 [estrogen receptor (ER)-positive, and wild-type p53)] and MDA-MB-231 (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 infra-red 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 α-santalol (20, and 40 μM) 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 α-santalol.

CONCLUSION:

The study reveals that survivin down-regulation by α-santalol in breast cancer cells is not mediated through the PI3K-AKT pathway.

• Authors: Ajay Bommareddy, Karryn Crisamore, Sarah Fillman, Sarah Brozena, James Steigerwalt, Terra Landis, Adam L Vanwert, Chandradhar Dwivedi
• Journal: Anticancer research (Anticancer Res) Vol. 35 Issue 10 Pg. 5353-7 (Oct 2015) ISSN: 1791-7530 [Electronic] Greece
• PMID: 26408696 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Chemical References

• Antineoplastic Agents
• BIRC5 protein, human
• Chromones
• Inhibitor of Apoptosis Proteins
• Morpholines
• Polycyclic Sesquiterpenes
• Sesquiterpenes
• Survivin
• santalol
• 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis
• Breast Neoplasms (drug therapy, metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Chromones (pharmacology)
• Down-Regulation
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Inhibitor of Apoptosis Proteins (metabolism)
• MAP Kinase Signaling System (drug effects)
• MCF-7 Cells
• Morpholines (pharmacology)
• Polycyclic Sesquiterpenes
• Sesquiterpenes (pharmacology)
• Survivin