Photodynamic therapy resistant human colon carcinoma HT29 cells show cross-resistance to UVA but not UVC light.
The isolation of photodynamic therapy (PDT)-resistant HT29 human colon adenocarcinoma cells has been reported previously. These PDT-resistant variants show increased expression of the Hsp27 and BNip3 proteins and a decreased expression of mutant p53 protein compared with parental HT29 cells. Because mutant p53 and increased expression of Hsp27 have been associated with resistance to various chemotherapeutic agents, whereas BNip3 is a potent inducer of apoptosis, we were interested in determining whether these PDT-resistant cells were cross-resistant to other cytotoxic agents. In the present report, we examined the colony survival of the PDT-resistant HT29 variants and several other clonal variants of HT29 cells to ultraviolet light (UV) treatment. The HT29 PDT-resistant variants showed cross-resistance to long-wavelength UVA (320-400 nm) but not to short-wavelength UVC (200-280 nm) light. Cell sensitivity to UVA or UVC was then correlated with Hsp27, BNip3 and mutant p53 protein levels in the PDT-resistant variants as well as in several clonal variants of HT29 cells that express different levels of Hsp27, BNip3 and mutant p53. We show that increased expression of Hsp27 and BNip3 and decreased expression of mutant p53 correlated with increased resistance to UVA. In contrast, increased expression of Hsp27 and BNip3 correlated with increased sensitivity to UVC, whereas increased expression of mutant p53 showed no significant correlation with sensitivity to UVC. These results suggest that the PDT-resistant HT29 cell variants are differentially sensitized to UVA compared with UVC due, in part at least, through the altered expression levels of BNip3, Hsp27 and mutant p53.
Zacal
Natalie
N
Department of Biology, McMaster University, Hamilton, ON, Canada.
Rainbow
Andrew J
AJ
D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D055551:HSP27 Heat-Shock Proteins; D019073:HT29 Cells; D006360:Heat-Shock Proteins / Q000032:analysis / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics*; D018832:Molecular Chaperones; D009154:Mutation; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics*; D010778:Photochemotherapy; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics*; D014466:Ultraviolet Rays
C090121:BNIP3 protein, human; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53