Modulation of proteomic profile in H295R adrenocortical cell line induced by mitotane.
Mitotane, 1,1-dichloro-2-(o-chlorophenyl)-2-(p-chloro-phenyl) ethane (o,p'-DDD), is a compound that represents the effective agent in the treatment of the adrenocortical carcinoma (ACC), able to block cortisol synthesis. In this type of cancer, the biological mechanism induced by this treatment remains still unknown. In this study, we have already shown a greater impairment in the first steps of the steroidogenesis and recognized a little effect on cell cycle. We also evaluated the variation of proteomic profile of the H295R ACC cell line, either in total cell extract or in mitochondria-enriched fraction after treatment with mitotane. In total cell extracts, triose phosphate isomerase, alpha-enolase, D-3-phosphoglycerate dehydrogenase, peroxiredoxin II and VI, heat shock protein 27, prohibitin, histidine triad nucleotide-binding protein, and profilin-1 showed a different expression. In the mitochondrial fraction, the following proteins appeared to be down regulated: aldolase A, peroxiredoxin I, heterogenous nuclear ribonucleoprotein A2/B1, tubulin-beta isoform II, heat shock cognate 71 kDa protein, and nucleotide diphosphate kinase, whereas adrenodoxin reductase, cathepsin D, and heat shock 70 kDa protein 1A were positively up-regulated. This study represents the first proteomic study on the mitotane effects on ACC. It permits to identify some protein classes affected by the drug involved in energetic metabolism, stress response, cytoskeleton structure, and tumorigenesis.
Stigliano
A
A
Endocrinology, II Faculty of Medicine, S Andrea Hospital, Sapienza University of Rome, Rome, Italy. antonio.stigliano@uniroma1.it
Cerquetti
L
L
Borro
M
M
Gentile
G
G
Bucci
B
B
Misiti
S
S
Piergrossi
P
P
Brunetti
E
E
Simmaco
M
M
Toscano
V
V
D000306:Adrenal Cortex Neoplasms / Q000378:metabolism*; D018268:Adrenocortical Carcinoma / Q000378:metabolism*; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008939:Mitotane / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013739:Testosterone / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D013739:Testosterone; D011374:Progesterone; D008939:Mitotane; D006854:Hydrocortisone