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Activation of stress-activated kinases and inhibition of PI 3-K/PKB and p70S6K mitogenic signaling pathway by photodynamic therapy in murine keratinocytes Tao, Jing-song

Abstract

Photodynamic therapy (PDT) is a new anti-cancer modality. It involves the use of photosensitizer molecules and a specific wavelength of visible light. The process of PDT generates singlet oxygen and other reactive oxygen intermediates (ROI). Cellular responses to PDT include induction of the early-response gene, release of cytokine, and apoptosis. Many of these cellular events are also known to be regulated by signaling pathways including members of the MAPK family and the PI 3-K/PKB/p70[sup S6K] mitogenic signaling pathway. We investigated the activation status of mitogen-activated protein kinases (MAPKs) and the phosphatidylinositol-3-kinase (PI3-K)/protein kinase B (PKB)/ p70[sup S6K] pathway following PDT treatment. We demonstrate here that PDT caused a marked, dose- and time-dependent activation of both stress-activated protein kinase (SAPK) and p38 HOG1 without affecting the activity of ERK1 or ERK2. However, under similar experimental conditions, PDT concomitantly inhibits the activity and phosphorylation of p70[sup S6K] in cells maintained in a serum-containing medium. In serum-starved Pam 212 cells, PDT inhibited the activation of PI3-K, PKB , and p70[sup S6K] induced by insulin treatment. At present, we do not understand the mechanisms for PDT-induced signaling events nor do we know the potential implications of our findings. However, some of the possible mechanisms and potential implications are discussed.

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