Melatonin interferes in the desmoplastic reaction in breast cancer by regulating cytokine production

Abstract

Melatonin exerts oncostatic effects on breast cancer by interfering with the estrogen signaling pathways.

Melatonin inhibits aromatase enzyme in breast cancer cells and fibroblasts.

In addition, melatonin stimulates the adipogenic differentiation of fibroblasts.

Our objective was to study whether melatonin interferes in the desmoplastic reaction by regulating some factors secreted by malignant cells, tumor necrosis factor (TNF)-α, interleukin (IL)-11, and interleukin (IL)-6.

To accomplish this, we co-cultured 3T3-L1 cells with MCF-7 cells. The addition of breast cancer cells to the co-cultures inhibited the differentiation of 3T3-L1 preadipocytes to mature adipocytes, by reducing the intracytoplasmic triglyceride accumulation, an indicator of adipogenic differentiation, and also stimulated their aromatase activity.

Melatonin counteracted the inhibitory effect on adipocyte differentiation and aromatase activity induced by MCF-7 cells in 3T3-L1 cells.

The levels of cytokines in the co-culture media were 10 times those found in culture of 3T3-L1 cells alone. Melatonin decreased the concentrations of cytokines in the media and counteracted the stimulatory effect induced by MCF-7 cells on the cytokine levels.

One millimolar melatonin induced a reduction in TNF-α, IL-6, and IL-11 mRNA expression in MCF-7 and 3T3-L1 cells.

The findings suggest that melatonin may play a role in the desmoplastic reaction in breast cancer through a downregulatory action on the expression of antiadipogenic cytokines, which decrease the levels of these cytokines.

Lower levels of cytokines stimulate the differentiation of fibroblasts and decrease both aromatase activity and expression, thereby reducing the number of estrogen-producing cells proximal to malignant cells.

 

 

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See also:

- About Melatonin;

- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonisn, 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;

- Neuroblastoma: Complete objective response to biological treatment;

- 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;

- The Di Bella Method (DBM) in the treatment of prostate cancer: a preliminary retrospective study of 16 patients and a review of the literature;

- Congenital fibrosarcoma in complete remission with Somatostatin, Retinoids, Vitamin D3, Vitamin E, Vitamin C, Melatonin, Calcium, Chondroitin sulfate associated with low doses of Cyclophosphamide in a 14-year Follow Up.