Caffeine induces apoptosis of osteosarcoma cells by inhibiting AKT/mTOR/S6K, NF-κB and MAPK pathways
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Updated: May 18, 2026

Development of a Human Preclinical Model of Osteoclastogenesis from Peripheral Blood Monocytes Co-cultured with Breast Cancer Cell Lines
Published on: September 13, 2017
Shinji Miwa1, Naotoshi Sugimoto, Norio Yamamoto
1Department of Orthopedic Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
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.
Insights
Caffeine demonstrates potential in treating osteosarcoma by inhibiting cancer cell proliferation. This study investigated caffeine
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Caffeine has shown promise in enhancing chemotherapy for malignant bone and soft tissue tumors.
- Previous research indicates caffeine influences key cellular pathways involved in tumor progression, including PTEN, AKT, BAX, caspase-3, and p53.
Purpose of the Study:
- To investigate the effects of caffeine on HOS osteosarcoma cell proliferation.
- To analyze caffeine's impact 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) signaling pathways in osteosarcoma cells.
Main Methods:
- Cell proliferation was assessed using the WST-8 assay.
- Western blot analyses were employed to evaluate the activity of NF-κB, mTOR, and MAPK pathways.
Main Results:
- Caffeine significantly inhibited the proliferation of HOS osteosarcoma cells.
- Caffeine suppressed the activity of NF-κB, AKT, mTOR/S6K, and ERK signaling pathways.
Conclusions:
- The findings support the therapeutic potential of caffeine in osteosarcoma treatment.
- Caffeine's anti-proliferative effects on osteosarcoma cells are mediated through the modulation of critical signaling pathways.
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