Selenium Decreases Thyroid Cancer Cell Growth by Increasing Expression of GADD153 and GADD34

• Published in: Nutrition and cancer Vol. 62; no. 1; pp. 66 - 73
• Main Authors: Kato, Meredith A, Finley, David J, Lubitz, Carrie C, Zhu, Baixin, Moo, Tracy-Ann, Loeven, Michael R, Ricci, Joseph A, Zarnegar, Rasa, Katdare, Meena, Fahey, Thomas J. III
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA Taylor & Francis Group 01.01.2010; Taylor& Francis; Taylor & Francis Ltd
• Subjects: anticarcinogenic activity; Antigens, Differentiation - genetics; apoptosis; Apoptosis - drug effects; Biological and medical sciences; Blotting, Western; Cancer; cell culture; Cell cycle; Cell Cycle - drug effects; Cell Cycle Proteins - genetics; Cell Division - drug effects; Cell growth; Cell Line, Tumor; cell proliferation; dietary mineral supplements; dietary minerals; Dietary supplements; DNA damage; DNA Damage - genetics; Endocrinopathies; Feeding. Feeding behavior; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Gene Expression - drug effects; gene overexpression; human cell lines; Humans; In Situ Nick-End Labeling; Malignant tumors; Medical sciences; Microarray Analysis; microarray technology; Mortality; neoplasms; Non tumoral diseases. Target tissue resistance. Benign neoplasms; nutrition-genotype interaction; Protein Phosphatase 1; Receptor, Epidermal Growth Factor - analysis; Receptor, Epidermal Growth Factor - genetics; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Selenium; Selenium - pharmacology; Selenomethionine - pharmacology; thyroid diseases; Thyroid gland; Thyroid Neoplasms - chemistry; Thyroid Neoplasms - pathology; Thyroid. Thyroid axis (diseases); Transcription Factor CHOP - analysis; Transcription Factor CHOP - genetics; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Endocrinopathy; Cell proliferation; Thyroid cancer; Cancerology; Thyroid diseases; Malignant tumor; Selenium; Gene expression; Tumor cell; Cancer
• ISSN: 0163-5581; 1532-7914
• DOI: 10.1080/01635580903191569

Selenium (Se) supplementation is reported to decrease the incidence and total mortality of cancer. Whereas in vitro and in vivo studies have shown a decrease in prostate, lung, and liver cancers, this has not been shown in thyroid cancer. ARO (anaplastic), NPA (BRAF positive papillary), WRO (BRAF negative papillary), and FRO (follicular) cells treated with 150 μM seleno-l-methionine (SM) were assessed for viability at 24, 48, and 72 h. Treated FRO cells were examined for cell cycle using flow cytometry, for apoptosis using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, and for gene expression using microarray. Genes identified as upregulated were confirmed by real-time PCR (RT-PCR) and proteins by Western blot analysis. SM treatment significantly decreased the proliferation of all cell lines. TUNEL assay showed no evidence of apoptosis, and flow cytometry showed a significant cell-cycle arrest in S (271% increase, P= 0.006) and G2/M (61% increase, P= 0.002) compared to control. Microarray revealed 21 differentially expressed genes with greater than twofold change. A relative overexpression of growth arrest and DNA damage inducible (GADD)34 and GADD153 in treated cells was confirmed with RT-PCR and Western blot. SM inhibits thyroid cancer cell proliferation through a time dependent upregulation of the GADD family of genes and arrest in S and G2/M phases of the cell cycle. This is the first report of selenium induced inhibition of thyroid cancer cell growth.