title: Rosemary extract reduces Akt/mTOR/p70S6K activation and inhibits proliferation and survival of A549 human lung cancer cells.
abstract: Compounds of plant origin and food components have attracted scientific attention for use as agents for cancer prevention and treatment. Rosemary extract contains polyphenols that were shown to have anti-cancer and other health benefits. The survival pathways of Akt, mammalian target of rapamycin (mTOR) and p70S6K, and the apoptotic protein poly ADP ribose polymerase (PARP) are key modulators of cancer cell growth and survival. In this study, we examined the effects of rosemary extract on proliferation, survival and apoptosis of human non-small cell lung cancer (NSCLC) cells and its influence on signaling events. Human NSCLC adenocarcinoma A549 cells were used. Cell proliferation and clonogenic survival were assessed using specific assays. Immunoblotting was used to examine total and phosphorylated levels of Akt, mTOR and p70S6K, and cleavage of PARP. Rosemary extract dose-dependently inhibited cell proliferation and reduced clonogenic survival of A549 cells, while PARP cleavage, an indicator of apoptosis, was enhanced. Rosemary extract significantly reduced total and phosphorylated/activated Akt, mTOR and p70S6K levels. In conclusion, rosemary extract inhibited proliferation, blocked clonogenic survival, and enhanced apoptosis of A549 lung cancer cells. These effects were associated with inhibition of Akt and downstream mTOR and p70S6K activity. Our data suggest that rosemary extract may have considerable anti-tumor and chemoprevention properties in lung cancer and deserves further systematic investigation in animal models of lung cancer.
authors.affiliation: Department of Health Sciences, Brock University, St. Catharines, Ontario, L2S 3A1, Canada.
authors.forename: Jessy
authors.initials: J
authors.lastname: Moore
authors.affiliation: Department of Health Sciences, Brock University, St. Catharines, Ontario, L2S 3A1, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Megaly
authors.affiliation: Department of Health Sciences, Brock University, St. Catharines, Ontario, L2S 3A1, Canada.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: MacNeil
authors.affiliation: Department of Kinesiology, Brock University, St. Catharines, Ontario, L2S 3A1, Canada; Centre for Bone and Muscle Health, Brock University, St. Catharines, ON, L2S 3A1, Canada.
authors.forename: Panagiota
authors.initials: P
authors.lastname: Klentrou
authors.affiliation: Department of Health Sciences, Brock University, St. Catharines, Ontario, L2S 3A1, Canada; Centre for Bone and Muscle Health, Brock University, St. Catharines, ON, L2S 3A1, Canada. Electronic address: ltsiani@brocku.ca.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Tsiani
mesh_terms: D000072283:A549 Cells; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002999:Clone Cells; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology*; D008954:Models, Biological; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D027542:Rosmarinus / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D010936:Plant Extracts; D011065:Poly(ADP-ribose) Polymerases; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases
keywords: Akt; Lung cancer; Proliferation; Rosemary extract; Survival; mTOR; p70S6K