Necrosis predominates in the cell death of human colon adenocarcinoma HT-29 cells treated under variable conditions of photodynamic therapy with hypericin.
Photodynamic therapy (PDT) represents a new rapidly-developing anticancer approach based on administration of a non- or weakly-toxic photosensitizer and its activation with light of appropriate wavelength. Hypericin, one of the promising photosensitizers, is known to induce apoptosis with high efficiency in various cell line models. However, here we report the prevalence of necrosis accompanied by suppression of caspase-3 activation in colon adenocarcinoma HT-29 cells exposed to an extensive range of PDT doses evoked by variations in two variables -- hypericin concentration and light dose. Necrosis was the principal mode of cell death despite different PDT doses and the absence of anti-apoptotic Bcl-2 expression, even if the same condition induced caspase-3 activity at similar toxicity in HeLa cells. Introduction of Bcl-2 into HT-29 cells invoked caspase-3 activation, changed the Bcl-X(L) expression pattern, increased the apoptosis ratio with no effect on overall toxicity, and supported arrest in the G(2)/M-phase of cell cycle. Since it is known that Bcl-2 suppression in HT-29 is reversible and linked to the over-expression of mutated p53 and also considering our data, we suggest that the mutation in p53 and events linked to this feature may play a role in cell death signalling in HT-29 colon cancer cells.
Mikes
Jaromír
J
Institute of Biology and Ecology, Faculty of Science, P J Safárik University, Moyzesova 11, 040 01, Kosice, Slovak Republic.
Kleban
Ján
J
Sacková
Veronika
V
Horváth
Viktor
V
Jamborová
Erika
E
Vaculová
Alena
A
Kozubík
Alois
A
Hofmanová
Jirina
J
Fedorocko
Peter
P
D000230:Adenocarcinoma / Q000628:therapy*; D000873:Anthracenes; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000628:therapy*; D004307:Dose-Response Relationship, Radiation; D015870:Gene Expression; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D008027:Light; D009336:Necrosis; D010569:Perylene / Q000031:analogs & derivatives* / Q000494:pharmacology; D010778:Photochemotherapy / Q000379:methods*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D000873:Anthracenes; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D010569:Perylene; C004965:hypericin; D053148:Caspase 3