title: Caffeine induces apoptosis of osteosarcoma cells by inhibiting AKT/mTOR/S6K, NF-κB and MAPK pathways.
abstract: We previously reported that caffeine-assisted chemotherapy improved the treatment of malignant bone and soft tissue tumours such as osteosarcoma. Caffeine affects tumour cells through various pathways, including phosphatase and tensin homolog deleted on chromosome 10 (PTEN), AKT, Bcl-2-associated X protein (BAX), caspase-3 and p53, and has therefore been indicated as being useful for the treatment of malignant tumours. Here, the effects of caffeine on the proliferation of HOS osteosarcoma cells were assessed by WST-8 assay, and the effects on the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase (MAPK) pathways were assessed by western blot analyses. Caffeine inhibited proliferation of HOS cells and suppressed NF-κB, AKT, mTOR/S6K and ERK activities. Our results support those from previous studies relating to the use of caffeine in the treatment of osteosarcoma.
authors.affiliation: Department of Orthopedic Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Miwa
authors.forename: Naotoshi
authors.initials: N
authors.lastname: Sugimoto
authors.forename: Norio
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Shirai
authors.forename: Hideji
authors.initials: H
authors.lastname: Nishida
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Hayashi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kimura
authors.forename: Akihiko
authors.initials: A
authors.lastname: Takeuchi
authors.forename: Kentaro
authors.initials: K
authors.lastname: Igarashi
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yachie
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsuchiya
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D002110:Caffeine / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism; D012516:Osteosarcoma / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D002110:Caffeine; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus