Antineoplastic effects of decitabine, an inhibitor of DNA promoter methylation, in adrenocortical carcinoma cells.

Abstract

HYPOTHESES:

Decitabine recovers expression of silenced genes on chromosome 11q13 and has antineoplastic effects in adrenocortical carcinoma (ACC) cells.

DESIGN:

NCI-H295R cells were treated with decitabine (0.1-1.0 microM) over 5 days. Cells were evaluated at 24-hour intervals for the effects of decitabine on ACC cell proliferation, cortisol secretion, and cell invasion. Expression was quantified for 6 genes on 11q13 (DDB1, MRPL48, NDUFS8, PRDX5, SERPING1, and TM7SF2) that were previously shown to be underexpressed in ACC.

SETTING:

Academic research. Study Specimen Human ACC cell line.

MAIN OUTCOME MEASURES:

Adrenocortical carcinoma cell proliferation, cortisol secretion, and cell invasion were measured using immunometric assays. Quantitative reverse transcription-polymerase chain reaction was used to measure gene expression relative to GAPDH.

RESULTS:

Decitabine inhibited ACC cell proliferation by 39% to 47% at 5 days after treatment compared with control specimens (P < .001). The inhibitory effect was cytostatic, time dependent, and dose dependent. Decitabine decreased cortisol secretion by 56% to 58% at 5 days after treatment (P = .02) and inhibited cell invasion by 64% at 24 hours after treatment (P = .03). Of 6 downregulated genes on 11q13, decitabine recovered expression of NDUFS8 (OMIM 602141) (P < .001) and PRDX5 (OMIM 606583) (P = .006).

CONCLUSIONS:

Decitabine exhibits antitumoral properties in ACC cells at clinically achievable doses and may be an effective adjuvant therapy in patients with advanced disease. Decitabine recovers expression of silenced genes on 11q13, which suggests a possible role of epigenetic gene silencing in adrenocortical carcinogenesis.

• Authors: Insoo Suh, Julie Weng, Gustavo Fernandez-Ranvier, Wen T Shen, Quan-Yang Duh, Orlo H Clark, Electron Kebebew
• Journal: Archives of surgery (Chicago, Ill. : 1960) (Arch Surg) Vol. 145 Issue 3 Pg. 226-32 (Mar 2010) ISSN: 1538-3644 [Electronic] United States
• PMID: 20231622 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• Decitabine
• Azacitidine

Topics

• Adrenocortical Carcinoma (drug therapy, pathology)
• Antimetabolites, Antineoplastic (pharmacology, therapeutic use)
• Azacitidine (analogs & derivatives, pharmacology, therapeutic use)
• DNA Methylation (drug effects)
• Decitabine
• Drug Screening Assays, Antitumor
• Humans
• Tumor Cells, Cultured