title: 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: Department of Pharmaceutical Sciences, South Dakota State University, Brookings, South Dakota, United States of America.
authors: Sreevidya
authors: S
authors: Santha
authors: Ajay
authors: A
authors: Bommareddy
authors: Brittny
authors: B
authors: Rule
authors: Ruth
authors: R
authors: Guillermo
authors: Radhey S
authors: RS
authors: Kaushik
authors: Alan
authors: A
authors: Young
authors: Chandradhar
authors: C
authors: Dwivedi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects*; D006801:Humans; D020287:In Situ Nick-End Labeling; D000081223:Polycyclic Sesquiterpenes; D011960:Receptors, Estrogen / Q000378:metabolism*; D012717:Sesquiterpenes / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D000081223:Polycyclic Sesquiterpenes; D011960:Receptors, Estrogen; D012717:Sesquiterpenes; C043206:santalol