Alpha-1-Antitrypsin Antagonizes Cisplatin-Induced Cytotoxicity in Prostate Cancer (PC3) and Melanoma Cancer (A375) Cell Lines.
Increased circulating alpha-1-antitrypsin (AAT) correlates with cancer stage/aggressiveness, but its role in cancer biology is unclear. We revealed antagonistic effect of AAT to cisplatin-induced cytotoxicity in prostate (PC3) and melanoma (A375) cancer cell lines. Moreover, AAT abrogated cytotoxicity of MEK inhibitor U0126 in PC3 cell line. Weaker antagonistic effect of AAT on cytotoxicity of PI3/Akt and NF-kB inhibitors was also observed. In addition, cisplatin increased AAT gene expression in transfected PC3 cells. However, AAT derived from transfected PC3 cells did not antagonize cisplatin-induced cytotoxicity. In conclusion, these results suggest possible association between high circulating AAT and cisplatin resistance.
Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, Belgrade, 11221, Serbia.
Mila
M
Ljujic
Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar despota Stefana 142, Belgrade, 11060, Serbia.
Sanja
S
Mijatovic
Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar despota Stefana 142, Belgrade, 11060, Serbia.
Mirna Z
MZ
Bulatovic
Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar despota Stefana 142, Belgrade, 11060, Serbia.
Marija
M
Mojic
Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar despota Stefana 142, Belgrade, 11060, Serbia.
Danijela
D
Maksimovic-Ivanic
Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, Belgrade, 11221, Serbia.
Dragica
D
Radojkovic
Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, Belgrade, 11221, Serbia. aleksandra.topic1@gmail.com.
Aleksandra
A
Topic
D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000515:alpha 1-Antitrypsin / Q000378:metabolism*
D016328:NF-kappa B; D000515:alpha 1-Antitrypsin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D002945:Cisplatin
Alpha-1-antitrypsin; Cisplatin; Melanoma cancer; Prostate cancer