Suppression of squamous cell carcinoma growth and differentiation by retinoids

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Published on Wednesday, 09 May 2018

Abstract

The epithelium of the oral cavity is mostly nonkeratinizing. However, it undergoes an abnormal squamous differentiation with keratinization during vitamin A deficiency or oral carcinogenesis.

Vitamin A analogues (retinoids) were found to be effective in preventing oral premalignant lesions and second primary cancers in the upper aerodigestive tract.

Further development of retinoids for prevention and therapy of squamous cell carcinoma (SCC) requires a better understanding of their mechanism action on the growth and differentiation of SCC cells. We used cultured head and neck SCC (HNSCC) cell lines as a model system.

Treatment of HNSCC cells with beta-all-trans-retinoic acid resulted in inhibition of growth (proliferation and colony formation) and suppression of squamous differentiation to varying degrees in the different cell lines.

Because some of the malignant HNSCC cells recapitulate the main characteristics of keratinocyte squamous differentiation and responsiveness to retinoids, they can serve as a model for investigating the mechanism underlying the effects of retinoids on cell growth and differentiation.

It is thought that nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs) mediate the above effects of retinoids by acting as DNA-binding transcription-modulating factors.

We found that HNSCC cell lines express several nuclear RAR and that their level could be modulated by retinoids in some cell lines. An inverse relationship was found between RAR-beta expression and squamous differentiation.

An analysis of RAR mRNA expression in head and neck cancer specimens revealed a decrease in RAR-beta in premalignant and malignant tissues relative to normal mucosa. The expression of this receptor increased in vivo after treatment with 13-cis-retinoic acid.

These results implicate the loss of RAR-beta expression in the development of head and neck cancer and suggest that RAR-beta could serve as an intermediate marker in prevention trials.

 

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See also:

- All-Trans-Retinoic Acid (ATRA - analogues and/or derivatives);

- The Di Bella Method (A Fixed Part - All-Trans Retinoic Acid, Analogues and/or Derivatives);

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

- The Di Bella Method (A Fixed Part - Alpha tocopheryl acetate/Vitamin E);

- 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;

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

- Neuroblastoma: Complete objective response to biological treatment;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in advanced non-small-cell lung cancer patients with low performance status;

- 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;

- 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.