Caffeine activates tumor suppressor PTEN in sarcoma cells

Miwa,Shinji; Sugimoto,Naotoshi; Shirai,Toshiharu; Hayashi,Katsuhiro; Nishida,Hideji; Ohnari,Issei; Takeuchi,Akihiko; Yachie,Akihiro; Tsuchiya,Hiroyuki

doi:10.3892/ijo.2011.1051

Caffeine activates tumor suppressor PTEN in sarcoma cells

Authors:
- Shinji Miwa
- Naotoshi Sugimoto
- Toshiharu Shirai
- Katsuhiro Hayashi
- Hideji Nishida
- Issei Ohnari
- Akihiko Takeuchi
- Akihiro Yachie
- Hiroyuki Tsuchiya
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Affiliations: Department of Orthopedic Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan, Department of Orthopedic Surgery, Graduate School of Medical Science, Kanazawa University, 13-1 Takaramachi, Kanazawa 920-8641, Japan
Published online on: May 23, 2011 https://doi.org/10.3892/ijo.2011.1051
Pages: 465-472

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Abstract

The tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a negative regulator of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Akt activation exerts a strong anti-apoptotic effect and inhibits key pro-apoptotic proteins. We investigated the effect of caffeine in the prevention of tumor cell proliferation and induction of cell death. We found that caffeine induced increased intracellular cAMP levels, PTEN activation and Akt inactivation, which together prevented proliferation of human osteosarcoma cells (MG63) and fibrosarcoma cells (HT1080). PTEN knockdown by siRNA reduced the effects of caffeine on Akt inactivation in osteosarcoma cells. These results indicate that the tumor suppressor PTEN signaling pathway contributes to the growth-inhibitory effect of caffeine on sarcoma cells. Our data suggest that caffeine and other drugs that act on this pathway could have promising therapeutic effects in the treatment of sarcoma patients.