Parathyroid hormone-related protein ameliorates death receptor-mediated apoptosis in lung cancer cells.
Parathyroid hormone-related protein (PTHrP) is expressed in more advanced, aggressive tumors and may play an active role in cancer progression. This study investigated the effects of PTHrP on apoptosis after UV irradiation, Fas ligation, or staurosporine treatment in BEN human squamous lung carcinoma cells. Cells at 70% confluency were treated for 24 h with 100 nM PTHrP-(1-34), PTHrP-(38-64), PTHrP-(67-86), PTHrP-(107-139), or PTHrP-(140-173) in media with serum, exposed for 30 min to UV-B radiation (0.9 mJ/cm2), and maintained for another 24 h. Caspase-3, caspase-8, and caspase-9 activities increased fivefold. Pretreatment with PTHrP-(1-34) and PTHrP-(140-173) ameliorated apoptosis after UV irradiation, as indicated by reduced caspase activities, increased cell protein, decreased nuclear condensation, and increased clonal survival. Other peptides had no effect on measures of apoptosis. PTHrP-(140-173) also reduced caspase activities after Fas ligation by activating antibody, but neither peptide had effects on caspase-3 or caspase-9 activity after 1 microM staurosporine. These data indicate that PTHrP-(1-34) and PTHrP-(140-173) protect against death receptor-induced apoptosis in BEN lung cancer cells but are ineffective against mitochondrial pathways. PTHrP contributes to lung cancer cell survival in culture and could promote cancer progression in vivo. The mechanism for the protective effect against apoptosis remains to be determined.
Hastings
Randolph H
RH
VA Medical Center (125 3350 La Jolla Village Dr., San Diego, CA 92161-5085, USA. rhhastings@ucsd.edu
Araiza
Flavio
F
Burton
Douglas W
DW
Zhang
Lu
L
Bedley
Maxwell
M
Deftos
Leonard J
LJ
D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D020169:Caspases / Q000187:drug effects* / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D005455:Fluorescent Antibody Technique; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D044162:Parathyroid Hormone-Related Protein / Q000494:pharmacology*; D014466:Ultraviolet Rays / Q000009:adverse effects
D044162:Parathyroid Hormone-Related Protein; D020169:Caspases