Visit our Expo - Redox and Inflammation signaling 2012

Session X : Cell death in cancer Poster X, 50
Role of MAPK kinase signalling pathways in photoinduced apoptosis in
cancer cells
Jarmila Kralova1, Michal Dvorak1, and Vladimir Kral2
1 Institute of Molecular Genetics, Academy of Sciences of the Czech Republic,
Flemingovo nám 2, 166 37 Prague 6, E-mail: kralova@img.cas.cz, mdvorak@img.cas.cz;
2 Department of Analytical Chemistry, Institute of Chemical Technology, Technická 5,
166 28 Prague 6, Czech Republic. E-mail: Vladimir.Kral@vscht.cz
Oxidative stress, such as photodynamic therapy (PDT), can act as an apoptosis inducer. In the
present study we investigated apoptotic pathways activated by novel photosensitizer
tetrakis(p-oligoethylenglycol) pentafluorophenyl porphyrin-mediated PDT in human
promyelocytic leukemia HL-60 and mouse mammary carcinoma 4T1. We show that p38 and
JNK MAP kinases are markedly activated during this process. Blocking the p38 MAPK
activation by specific inhibitor SB203580 or PD169316 resulted in the suppression of
apoptosis contrary to JNK blocking by specific inhibitor SP600125 that rather led to its
enhancement. The onset of apoptotic events + cytochrome c release, caspase activation and
dramatic changes in the expression of some Bcl-2 family members (down-regulation of Bcl-2
and Bak, cleavage of Bad and Mcl-1, activation of pro-apoptotic Bid protein) appeared
concurrently within 30 min following PDT treatment in a time-response manner. Apoptosis
could also be partly inhibited by overexpression of Bcl-2. Pre-incubation of cells with caspase
family inhibitor, fluoromethylketone (Z-VAD-FMK), significantly reduced apoptosis, while
individual caspase-specific inhibitors had only a partial effect. These observations indicate
that multiple signalling pathways, which play diverse roles in the apoptotic process, are
activated during PDT in a cell type-specific manner. The p38 MAPK signalling pathway
seems to be directly involved in the activation, while the Akt – JNK1 pathway in the cellular
resistance against PDT-induced apoptosis. Multi-functional signalling network enables
additional augmentation of the apoptotic process e.g. through activation of pro-apoptotic Bcl-
2 family protein Bid and caspase 8.
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