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- Title
Promotion of photodynamic therapy-induced apoptosis by stress kinases.
- Authors
Xue, Liang-yan; He, Jin; Oleinick, Nancy L
- Abstract
Photodynamic therapy (PDT), a cancer treatment that employs a photosensitizer and visible light, induces apoptosis in murine LY-R leukemic lymphoblasts and in Clio cells, but the rate and extent of apoptosis are much greater in LY-R cells. Three MAPK family members, ERK1/ERK2, SAPK/JNK, and p38/HOG, are important intermediates in signal transduction pathways. To ascertain whether activation of one or more MAPKs could mediate PDT-induced apoptosis, Western blot analysis has been performed on the proteins of LY-R and Clio cells at various times following lethal (90-99% cell kill) doses of PDT photosensitized by the phthalocyanine Pc 4. The blots were probed with antibodies to each of the proteins as well as antibodies specific for the activated (phosphorylated)forms of each kinase. Of the three MAPK types, only the p46 and p54 SAPK/JNKs were found to be activated by PDT in LY-R cells, with a maximum ∼threefold increase in the content of the phosphorylated forms reached in 30-60 min. An even larger relative activation was observed in Clio cells. PDT did not affect ERK and p38/HOG activation in LY-R cells. In the case of Clio cells, however, ERK2 was slightly activated at 5 min postPDT, then declined, and p38/HOG was strongly activated from 5 to 60 min post-PDT. A specific inhibitor (PD98059) of MEK1, the kinase that activates ERK, had little or no effect on PDTinduced apoptosis in either LY-R or Clio cells. In contrast, a specific inhibitor of p38/HOG (SB202190) blocked PDTinduced apoptosis in LY-R cells with a lesser effect in Clio cells. The results suggest that both the SAPK and p38/HOG cascades can be stimulated by PDT and that the latter participates in both rapid and slow PDT-induced apoptosis. Furthermore, the high level of constitutively active p38/HOG in LY-R cells may poise those cells for rapid activation of apoptosis following PDT.
- Subjects
APOPTOSIS; PHOTOCHEMOTHERAPY; PROTEIN kinases
- Publication
Cell Death & Differentiation, 1999, Vol 6, Issue 9, p855
- ISSN
1350-9047
- Publication type
Article
- DOI
10.1038/sj.cdd.4400558