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: Shinji Miwa, Naotoshi Sugimoto, Norio Yamamoto, Toshiharu Shirai, Hideji Nishida, Katsuhiro Hayashi, Hiroaki Kimura, Akihiko Takeuchi, Kentaro Igarashi, Akihiro Yachie, Hiroyuki Tsuchiya
• Journal: Anticancer research (Anticancer Res) Vol. 32 Issue 9 Pg. 3643-9 (Sep 2012) ISSN: 1791-7530 [Electronic] Greece
• PMID: 22993301 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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