Comparison of caspase genes for the induction of apoptosis following gene delivery.
The polycation poly(ethylenimine) (PEI) was used to deliver the plasmids coding for various combinations of caspases to Cox-2 overexpressing cancer cell lines. It was found that the expression of the delivered genes, controlled by the Cox-2 promoter, correlated with the expression of the endogenous Cox-2 gene in each cell line in a relatively linear manner. Among the various caspase combination regimens, the combination of caspase 3 plus caspase 9 proved to be the most effective because of an apparent synergy between the two gene products, and produced phosphatidylserine flipping in addition to fragmentation of genomic DNA. Caspase 1 appeared to work independently of either caspases 3 or 9, as no synergistic effect was observed. Transfections with genes coding for granzyme B and caspase 8 yielded a lesser amount of cell death. The delivery of a combination of caspase genes could be readily moved to in vivo research of bladder and colon cancer treatments, and holds great applicability to a wide array of additional tumor types.
Zhang
Xiujuan
X
Laboratory for Gene Therapy and Cellular Engineering, Department of Chemical and Biomolecular Engineering, Tulane University, 6823 St. Charles Avenue, 300 Lindy Boggs Center, New Orleans, LA 70118, USA.
Turner
Curlicia
C
Godbey
W T
WT
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis; D002295:Carcinoma, Transitional Cell / Q000201:enzymology; D020169:Caspases / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D003001:Cloning, Molecular; D003110:Colonic Neoplasms / Q000201:enzymology; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000201:enzymology; D016650:Fluorescein-5-isothiocyanate; D053804:Granzymes / Q000235:genetics / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D051379:Mice; D011094:Polyethyleneimine / Q000009:adverse effects; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection; D001749:Urinary Bladder Neoplasms / Q000201:enzymology
D012333:RNA, Messenger; D011094:Polyethyleneimine; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D053804:Granzymes; C509214:Gzmb protein, mouse; D020169:Caspases; D016650:Fluorescein-5-isothiocyanate