Caspase-1 activity as a possible predictor of apoptosis induced by cisplatin in gastric cancer cells.
Recent studies have shown that caspases, which are cystein proteases, elevate endonuclease activity and induce apoptosis. Caspase-1, an interleukin-1beta converting enzyme, has been reported to be related with anti-cancer drug induced apoptosis as well as with caspase-3. To elucidate the caspase-1 activity, which might be a predictor for the effect of chemotherapy, we examined the changes of caspase-1 activity induced after exposure to cisplatin (CDDP) in six gastric cancer cell lines. A high correlation between the 50% inhibitory concentration (IC50) and caspase-1 activity ratio was shown (r=0.83, p=0.041) (caspase-1 activity ratio: the caspase-1 activity of cells at 4 h after CDDP treatment/the caspase-1 activity of untreated cells). Further, we examined the correlation between caspase-1 activity and apoptosis induced by CDDP in two cell lines that have very different CDDP sensitivities; OCUM-2M and OCUM-2M/DDP (IC50; 0. 85+/-0.4 microg/ml and 9.0+/-1.2 microg/ml, respectively). The apoptotic index of OCUM-2M was significantly higher than that of OCUM-2M/DDP (19.8+/-3.8% vs. 4.5+/-1.2%, respectively; p=0.0005). In both cell lines, caspase-1 activity began to increase immediately after exposure to CDDP and peaked at approximately 4 h after cessation of exposure to CDDP, and gradually decreased thereafter. The caspase-1 activity of OCUM-2M was approximately 1.8-times higher than that of OCUM-2M/DDP at 4 h after exposure to CDDP. Taken together, our results indicate that evaluating the changes of caspase-1 activity after exposure to CDDP may be useful to predict apoptosis following CDDP treatment in gastric cancer cells.
Muguruma
K
K
First Department of Surgery, Institute of Geriatrics and Medical Science, Osaka City University Medical School, Abeno-ku, Osaka 545-8585, Japan.
Nakata
B
B
Yanagawa
K
K
Nitta
A
A
Yashiro
M
M
Onoda
N
N
Hirakawa
K
K
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D020170:Caspase 1 / Q000378:metabolism*; D002945:Cisplatin / Q000494:pharmacology*; D004247:DNA / Q000032:analysis; D020287:In Situ Nick-End Labeling; D020128:Inhibitory Concentration 50; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein
D000970:Antineoplastic Agents; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D004247:DNA; D020170:Caspase 1; D002945:Cisplatin