title: 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.
  
  
  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.
  
  
  CONCLUSIONS
  The study reveals that survivin down-regulation by α-santalol in breast cancer cells is not mediated through the PI3K-AKT pathway.
authors.affiliation: Department of Pharmaceutical Sciences, Nesbitt School of Pharmacy, Wilkes University, Wilkes-Barre, PA, U.S.A. ajay.bommareddy@wilkes.edu.
authors.forename: Ajay
authors.initials: A
authors.lastname: Bommareddy
authors.affiliation: Department of Pharmaceutical Sciences, Nesbitt School of Pharmacy, Wilkes University, Wilkes-Barre, PA, U.S.A.
authors.forename: Karryn
authors.initials: K
authors.lastname: Crisamore
authors.affiliation: Department of Pharmaceutical Sciences, Nesbitt School of Pharmacy, Wilkes University, Wilkes-Barre, PA, U.S.A.
authors.forename: Sarah
authors.initials: S
authors.lastname: Fillman
authors.affiliation: Department of Pharmaceutical Sciences, Nesbitt School of Pharmacy, Wilkes University, Wilkes-Barre, PA, U.S.A.
authors.forename: Sarah
authors.initials: S
authors.lastname: Brozena
authors.affiliation: Department of Pharmaceutical Sciences, Nesbitt School of Pharmacy, Wilkes University, Wilkes-Barre, PA, U.S.A.
authors.forename: James
authors.initials: J
authors.lastname: Steigerwalt
authors.affiliation: Department of Pharmaceutical Sciences, Nesbitt School of Pharmacy, Wilkes University, Wilkes-Barre, PA, U.S.A.
authors.forename: Terra
authors.initials: T
authors.lastname: Landis
authors.affiliation: Department of Pharmaceutical Sciences, Nesbitt School of Pharmacy, Wilkes University, Wilkes-Barre, PA, U.S.A.
authors.forename: Adam L
authors.initials: AL
authors.lastname: Vanwert
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, SD, U.S.A.
authors.forename: Chandradhar
authors.initials: C
authors.lastname: Dwivedi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D061986:MCF-7 Cells; D009025:Morpholines / Q000494:pharmacology; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes / Q000494:pharmacology*; D000077022:Survivin
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D002867:Chromones; D051034:Inhibitor of Apoptosis Proteins; D009025:Morpholines; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes; D000077022:Survivin; C043206:santalol; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
keywords: PI3K-AKT pathway; caspase-3; survivin; α-santalol