Caffeine induces apoptosis of osteosarcoma cells by inhibiting AKT/mTOR/S6K, NF-κB and MAPK pathways

Anticancer Res. 2012 Sep;32(9):3643-9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / enzymology
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology
  • Caffeine / pharmacology*
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Humans
  • MAP Kinase Signaling System / drug effects*
  • NF-kappa B / metabolism
  • Osteosarcoma / drug therapy*
  • Osteosarcoma / enzymology
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism
  • Sirolimus / pharmacology
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TOR Serine-Threonine Kinases / metabolism


  • NF-kappa B
  • Caffeine
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Sirolimus