Antineoplastic effects of α-santalol on estrogen receptor-positive and estrogen receptor-negative breast cancer cells through cell cycle arrest at G2/M phase and induction of apoptosis.

Abstract

Anticancer efficacy and the mechanism of action of α-santalol, a terpenoid isolated from sandalwood oil, were investigated in human breast cancer cells by using p53 wild-type MCF-7 cells as a model for estrogen receptor (ER)-positive and p53 mutated MDA-MB-231 cells as a model for ER-negative breast cancer. α-Santalol inhibited cell viability and proliferation in a concentration and time-dependent manner in both cells regardless of their ER and/or p53 status. However, α-santalol produced relatively less toxic effect on normal breast epithelial cell line, MCF-10A. It induced G2/M cell cycle arrest and apoptosis in both MCF-7 and MDA-MB-231 cells. Cell cycle arrest induced by α-santalol was associated with changes in the protein levels of BRCA1, Chk1, G2/M regulatory cyclins, Cyclin dependent kinases (CDKs), Cell division cycle 25B (Cdc25B), Cdc25C and Ser-216 phosphorylation of Cdc25C. An up-regulated expression of CDK inhibitor p21 along with suppressed expression of mutated p53 was observed in MDA-MB-231 cells treated with α-santalol. On the contrary, α-santalol did not increase the expression of wild-type p53 and p21 in MCF-7 cells. In addition, α-santalol induced extrinsic and intrinsic pathways of apoptosis in both cells with activation of caspase-8 and caspase-9. It led to the activation of the executioner caspase-6 and caspase-7 in α-santalol-treated MCF-7 cells and caspase-3 and caspase-6 in MDA-MB-231 cells along with strong cleavage of poly(ADP-ribose) polymerase (PARP) in both cells. Taken together, this study for the first time identified strong anti-neoplastic effects of α-santalol against both ER-positive and ER-negative breast cancer cells.

• Authors: Sreevidya Santha, Ajay Bommareddy, Brittny Rule, Ruth Guillermo, Radhey S Kaushik, Alan Young, Chandradhar Dwivedi
• Journal: PloS one (PLoS One) Vol. 8 Issue 2 Pg. e56982 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23451128 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Polycyclic Sesquiterpenes
• Receptors, Estrogen
• Sesquiterpenes
• santalol

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Breast Neoplasms (metabolism, pathology)
• Cell Division (drug effects)
• Cell Line, Tumor
• Cell Proliferation
• Female
• Flow Cytometry
• G2 Phase (drug effects)
• Humans
• In Situ Nick-End Labeling
• Polycyclic Sesquiterpenes
• Receptors, Estrogen (metabolism)
• Sesquiterpenes (pharmacology)