Identification of novel transcriptional networks in response to treatment with the anticarcinogen 3H-1,2-dithiole-3-thione

Abstract

3H-1,2-dithiole-3-thione (D3T), an inducer of antioxidant and phase 2 genes, is known to enhance the detoxification of environmental carcinogens, prevent neoplasia, and elicit other protective effects. However, a comprehensive view of the regulatory pathways induced by this compound has not yet been elaborated. Fischer F344 rats were gavaged daily for 5 days with vehicle or D3T (0.3 mmol/kg). The global changes of gene expression in liver were measured with Affymetrix RG-U34A chips. With the use of functional class scoring, a semi-supervised method exploring both the expression pattern and the functional annotation of the genes, the Gene Ontology classes were ranked according to the significance of the impact of D3T treatment. Two unexpected functional classes were identified for the D3T treatment, cytosolic ribosome constituents with 90% of those genes increased, and cholesterol biosynthesis with 91% of the genes repressed. In another novel approach, the differentially expressed genes were evaluated by the Ingenuity computational pathway analysis tool to identify specific regulatory networks and canonical pathways responsive to D3T treatment. In addition to the known glutathione metabolism pathway (P = 0.0011), several other significant pathways were also revealed, including antigen presentation (P = 0.000476), androgen/estrogen biosynthesis (P = 0.000551), fatty acid (P = 0.000216), and tryptophan metabolism (P = 0.000331) pathways. These findings showed a profound impact of D3T on lipid metabolism and anti-inflammatory/immune-suppressive response, indicating a broader cytoprotective effect of this compound than previously expected.

Role of Gα12 and Gα13 as Novel Switches for the Activity of Nrf2, a Key Antioxidative Transcription Factor

“…In the PCR assays, UGT1A1, 1A6, GCLM, and NQO1 gene transcripts were included because the genes comprised the functional AREs (our customer-made microarrays did not cover all of the genes containing functional AREs). The observation showing strong induction in the genes participating in glutathione metabolism (i.e., Gsta1, Gsta3, Gsta4, Gstp1, Gclc, Gclm, G6pd, and Gsr) (14) supports the significant role of G␣ 12 in Nrf2 activity. Canonical pathway analysis successfully confirmed glutathione and cysteine metabolism as the major pathways influenced by G␣ 12 deficiency in combination with t-BHQ treatment.…”

Moderate strength (0.23–0.28 T) static magnetic fields (SMF) modulate signaling and differentiation in human embryonic cells

“…A simple inspection of transcriptional changes (for example, the top 5 up- and down-regulated genes under each exposure condition listed in Tables 2, 3, and 4) did not lead to any obvious insights into the over-riding effects of SMF however. Therefore, to flesh out this hypothesis, the Ingenuity Pathway Analysis software tool [21,26] was used to analyze the microarray data resulting in the identification of nine networks that responded to SMF exposure in hEDB LVED cells (Table 5; data analysis is shown for cells subject to five days of continuous SMF exposure and the annotated networks are provided in Additional file 1). Several of these pathways reflected known biological responses to magnetic exposure.…”

Gene Expression Changes in Spleens and Livers of Tumour-Bearing Mice Suggest Delayed Inflammation and Attenuated Cachexia in Response to Oil Palm Phenolics

“…Curcumin also inhibited immunostimulatory functions of dendritic cells [43]. In addition, the cancer chemopreventive agent dithiolethione was found to mediate its anti-cancer effects via downregulation of antigen presentation genes [44]. Hence, OPP may help delay inflammation in the prevention or treatment of cancer.…”