Expression of TXNIP in Cancer Cells and Regulation by 1,25(OH)₂D₃: Is It Really the Vitamin D₃ Upregulated Protein?

Abstract

Thioredoxin-interacting protein (TXNIP) was originally identified in HL-60 cells as the vitamin D₃ upregulated protein 1, and is now known to be involved in diverse cellular processes, such as maintenance of glucose homeostasis, redox balance, and apoptosis.

Besides the initial characterization, little is known about if and how 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃] induces TXNIP expression.

We therefore screened multiple cancerous cell lines of different tissue origins, and observed induction, repression, or no change in TXNIP expression in response to 1,25(OH)₂D₃.

In-depth analyses on HL-60 cells revealed a rapid and transient increase in TXNIP mRNA levels by 1,25(OH)₂D₃ (3-24 h), followed by a clear reduction at later time points.

Furthermore, a strong induction in protein levels was observed only after 96 h of 1,25(OH)₂D₃ treatment. Induction of TXNIP expression by 1,25(OH)₂D₃ was found to be dependent on the availability of glucose in the culture medium, as well as the presence of a functional glucose transport system, indicating an inter-dependence of 1,25(OH)₂D₃ actions and glucose-sensing mechanisms.

Moreover, the inhibition of de novo protein synthesis by cycloheximide reduced TXNIP half-life in 24 h, but not in 96 h-1,25(OH)₂D₃-treated HL-60 cells, demonstrating a possible influence of 1,25(OH)₂D₃ on TXNIP stability in long-term treatment.

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See also:

- Vitamin D (analogues and/or derivatives) and cancer;

- The Di Bella Method (A Fixed Part - Dihydrotachysterol/synthetic Vitamin D3);

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- Pancreatic Adenocarcinoma: clinical records on 17 patients treated with Di Bella's Method;

- The Di Bella Method Increases by the 30% the survival rate for Pancreas tumors and for this reason should be proposed as first line therapy for this type of cancer;

- Cyclophosphamide plus Somatostatin, Bromocriptin, Retinoids, Melatonin and ACTH in the Treatment of Low-grade Non-Hodgkin’s Lymphomas at Advanced Stage: Results of a Phase II Trial;

- Relapse of High-Grade Non-Hodgkin’s Lymphoma After Autologous Stem Cell Transplantation: A Case Successfully Treated With Cyclophosphamide Plus Somatostatin, Bromocriptine, Melatonin, Retinoids, and ACTH;

- Low-grade Non-Hodgkin Lymphoma at Advanced Stage: A Case Successfully Treated With Cyclophosphamide Plus Somatostatin, Bromocriptine, Retinoids, and Melatonin;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 55 cases of Lymphomas;

- Large B-cells Non-Hodgkin's Lymphoma, Stage IV-AE: a Case Report;

- Non-Hodgkin's Lymphoma, Stage III-B-E: a Case Report;

- Chronic Lymphocytic Leukemia: Long-Lasting Remission with Combination of Cyclophosphamide, Somatostatin, Bromocriptine, Retinoids, Melatonin, and ACTH;

- Complete objective response, stable for 5 years, with the Di Bella Method, of multiple-metastatic carcinoma of the breast;

- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma.

Expression of TXNIP in Cancer Cells and Regulation by 1,25(OH)₂D₃: Is It Really the Vitamin D₃ Upregulated Protein? - Supplementary File