Retinoids induce growth inhibition and apoptosis in mast cell tumor cell lines

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Published on Tuesday, 18 May 2021

Abstract

Retinoids are well recognized as promising antitumor agents in humans. However, there have only been a few reports about the effect of retinoids in canine cancers. To investigate the antitumor effect of retinoids on mast cell tumors (MCT), inhibitory effect on cell growth and induction of apoptosis were examined in vitro.

Although sensitivity of these cells differed among the cells, the growth of three MCT cell lines (CoMS, CM-MC and VI-MC) were inhibited dose dependently when they were treated with retinoids.

FACS analysis of PI-stained nuclei revealed an apoptotic fraction in CM-MC cells about 30% when treated with retinoids, while those of control cells were less than 5%. Caspase-3 activation was observed after retinoid treatment in CM-MC cells. This was confirmed by inhibiting the retinoid-induced apoptosis using the pan-caspase inhibitor, ZVAD-FMK. Both retinoid receptors, RARs and RXRs, were detected by immunoprecipitation followed by western blot analysis in all the three MCT cells.

These data suggests that retinoids inhibit the growth of MCTs partly through apoptosis, and this growth inhibition by retinoids may be mediated by RARs and RXRs.

We conclude that retinoid may be a potential adjunctive chemotherapeutic agent for the treatment of canine MCT.

 



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See also:

- Official Web Site: The Di Bella Method;


 


- The Di Bella Method (A Fixed Part - All-Trans Retinoic Acid, Analogues and/or Derivatives - Approximately 60mg per day orally: 40mg per day Beta-Carotene/β-Carotene, 10mg per day ATRA and 10mg per day Axerophthol palmitate);

- All-Trans-Retinoic Acid (ATRA - analogues and/or derivatives) - In vitro, review and in vivo publications;

- Solution of retinoids in vitamin E in the Di Bella Method biological multitherapy;

- The Di Bella Method (A Fixed Part - Cyclophosphamide 50mg tablets and/or Hydroxyurea 500mg tablets, one or two per day);


 


- The Synergism of Somatostatin, Melatonin, Vitamins Prolactin and Estrogen Inhibitors Increased Survival, Objective Response and Performance Status In 297 Cases of Breast Cancer;

- 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;

- Recurrent Glioblastoma Multiforme (grade IV – WHO 2007): a case of complete objective response achieved by means of the concomitant administration of Somatostatin and Octreotide – Retinoids – Vitamin E – Vitamin D3 – Vitamin C – Melatonin – D2 R agonists (Di Bella Method – DBM) associated with Temozolomide;

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- 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;

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

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

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- 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.