1,25-dihydroxyvitamin D3 synthetic analogs inhibit spontaneous metastases in a 1,2-dimethylhydrazine-induced colon carcinogenesis model

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Published on Tuesday, 02 January 2018

Abstract

In order to substantiate the role of vitamin D applicability for the prevention of colon cancer and its spontaneous metastases, the effect of 1,25-dihydroxyvitamin D3 and its synthetic analogs, 1, 25-dihydroxy-16,23Z-diene-26,27-hexafluoro-D3 (Ro 25-5317) and 1, 25-dihydroxy-16,23E-diene-26,27-hexafluoro-19-nor-D3 (Ro 25-9022), have been evaluated in a 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis model in Sprague-Dawley rats.

In animals maintained on 2.75 nmol/kg 1,25-dihydroxyvitamin D3 diet no statistical difference was seen in tumor incidence when compared with control while in animals on 3.0 nmol/kg 1,25-dihydroxyvitamin D3 diet, the incidence of tumors was significantly lower.

In animals maintained on 3.0 nmol/kg Ro 25-5317 diet also no statistical difference was seen in tumor incidence compared with control while in animals on 3. 5 nmol/kg Ro 25-5317 diet the incidence of tumors was significantly lower.

The incidence of tumors in the group of animals maintained on 3.0 nmol/kg and 3.5 nmol/kg Ro 25-9022 was significantly lower, at 32.1% and 27.6% respectively, compared to control.

In the two groups of animals maintained on the 1,25-dihydroxyvitamin D3 diet no significant difference in the incidence of metastasis was seen. In the group of animals maintained on 3.0 nmol/kg Ro 25-5317 diet only regional metastases were seen. However, no metastases developed in the rats on 3.5 nmol/kg Ro 25-5317 diet.

After administration of 3.0 nmol/kg Ro 25-9022 diet, metastases developed in a significantly less number of animals while no metastases occurred in the rats maintained on the 3.5 nmol/kg Ro 25-9022 diet.

The above studies will provide a scientific basis for the progression into further clinical trials in the treatment, and/or chemoprevention of human colorectal cancer.

 

 

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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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- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in chemotherapy-pretreated patients with advanced lung adenocarcinoma and low performance status;

- Observations on the Report of a case of pulmonary adenocarcinoma with lymph node, hepatic and osseus metastasis;

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

- The Di Bella Method DBM improved survival objective response and performance status in a retrospective observational clinical study on 23 tumours of the head and neck;

- 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;

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