Targeted inhibition of p38α MAPK suppresses tumor-associated endothelial cell migration in response to hypericin-based photodynamic therapy

Hypericin-mediated photodynamic therapy induces apoptosis of myoloma SP2/0 cells depended on caspase activity in vitro

“…Hypericin-mediated PDT has obtained increasing interests as a potential treatment for various cancers [17][18][19]. Currently, multiple pathways have been found to involved in the tumor cell death program induced by hypericin-mediated PDT, such as mitochondrial pathway [20,21], lysosomal damage [22], alternation of intracellular pH level [23,24], Bcl-2 phosphorylation by CDK-1 [25] as well as the increase of intracellular Ca2+ stimulated apoptosis [26][27][28]. However, the mechanism underlying hypericin-mediated PDT for MM suppression has been not clarified clearly.…”

Photodynamic therapy with an endocytically located photosensitizer cause a rapid activation of the mitogen-activated protein kinases extracellular signal-regulated kinase, p38, and c-Jun NH2 terminal kinase with opposing effects on cell survival

“…On the other hand, p38 phosphorylation has been shown to protect cells from p38 Induces Death but JNK Rescues Cells from TPPS 2a -PDT Hypericin-PDT (19), in contrast to Photofrin-PDT where p38 activation seems to have no influence on the treatment outcome (29). Activation of p38 by PDT has also been associated with induction of VEGF following both hypericin-mediated and benzoporphyrin derivative monoacid ring A -mediated PDT (30,31). The present report indicates that activation of p38 is an immediate death signal after TPPS 2a -PDT.…”

Photochemically stimulated drug delivery increases the cytotoxicity and specificity of EGF–saporin

“…If p38 inhibition does not influence on photochemicallyinduced rupture of endosomes and lysosomes, inhibition of photochemical induced death signals, as the p38 activation, in PCI of genes is likely to increase the fraction of surviving transducable cells and may in this way increase the spesificity of the treatment. PDT induced p38 activation has by others also been associated with induction of VEGF using both BPD and Hypericin as photosensitizers (Hendrickx et al 2005, Solban et al 2006) and activation of p38 after hypericin PDT is in addition shown to upregulate cyclooxygenase-2 (Hendrickx et al 2003) and heme-oxygenase 1 (Kocanova et al 2007). Induction of both VEGF (Ferrara & Gerber 2001, Kowanetz & Ferrara 2006, COX-2 (Bakhle 2001) and heme-oxygenase (Jozkowicz et al 2007 Protein NuTu-19 WiDr A-431 p-EGFR decrease no effect no effect EGFR no effect no effect no effect p-ERK increase increase decrease ERK no effect no effect no effect p-JNK increase not detected not detected JNK no effect no effect no effect p-p38 increase increase increase P38 no effect no effect no effect Protein NuTu-19 A-431 p-EGFR decrease decrease EGFR decrease no effect p-ERK increase -ERK no effect -p-JNK --JNK no effect -p-p38 increase -P38 no effect - …”