Modulation of all-trans retinoic acid-induced MiRNA expression in neoplastic cell lines: a systematic review

Abstract

BACKGROUND: Cancer is a genetic and epigenetic disease that involves inactivation of tumor suppressor genes and activation of proto-oncogenes. All-trans retinoic acid (ATRA) is an isomer of retinoic acid involved in the onset of differentiation and apoptosis of a number of normal and cancer cells, functioning as an anti-cancer agent in several neoplasms. Ectopic changes in the expression of certain microRNAs (miRNAs) occur in response to ATRA, leading to phenotypic alterations in neoplastic cell lines. Moreover, the modulation of miRNA patterns upon ATRA-treatment may represent an effective chemopreventive and anti-cancer therapy strategy. The present systematic review was performed to provide an overview of the modulation of ATRA-induced miRNA expression in different types of neoplastic cells and identify the efficacy of intervention factors (i.e., concentration and duration of treatment) and how they influence expression profiles of oncogenesis-targeting miRNAs.

METHODS: A systematic search was conducted according to the PRISMA statement via the US National Library of Medicine MEDLINE/PubMed bibliographic search engine.

RESULTS: The search identified 31 experimental studies involving human cell lines from nine different cancer types (neuroblastoma, acute myeloid leukemia, breast cancer, lung cancer, pancreatic cancer, glioma, glioblastoma, embryonal carcinoma, and colorectal cancer) treated with ATRA at concentrations ranging from 10- 3 μmol/L to 102 μmol mol/L for 24 h to 21 days.

CONCLUSION: The concentrations used and the duration of treatment of cancer cells with ATRA varied widely. The presence of ATRA in the culture medium of cancer cells was able to modulate the expression of more than 300 miRNAs, and inhibit invasive behavior and deregulated growth of cancer cells, resulting in total tumor remission in some cases. ATRA may thus be broadly effective for neoplasm treatment and prevention, although these studies may not accurately represent in vivo conditions. Additional studies are required to elucidate ATRA-induced miRNA modulation during neoplasm treatment.

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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 - Alpha tocopheryl acetate/Vitamin E, approximately 20 grams per day orally);

- Cancer and Vitamin E (analogues and/or derivatives) and cancer - In vitro, review and in vivo publications;

- The Di Bella Method (A Variable Part - Omega 3 Essential/Unsaturated Fatty Acids. From 1.5 grams up to 3.0 grams per day orally);

- The Di Bella Method (A Fixed Part - Somatostatin, Octreotide, Sandostatin LAR, analogues and/or derivatives);

- Somatostatin in oncology, the overlooked evidences - In vitro, review and in vivo publications;

- Publication: Over-Expression of GH/GHR in Breast Cancer and Oncosuppressor Role of Somatostatin as a Physiological Inhibitor (from Di Bella's Foundation);

- Publication: The over-expression of GH/GHR in tumour tissues with respect to healthy ones confirms its oncogenic role and the consequent oncosuppressor role of its physiological inhibitor, somatostatin: a review of the literature (from Di Bella's Foundation);

- Publication: The Entrapment of Somatostatin in a Lipid Formulation: Retarded Release and Free Radical Reactivity (from Di Bella's Foundation);

- The Di Bella Method (A Fixed Part - Melatonin tablets. From 30-40mg/day up to 200mg/day orally in patients with advanced stage of cancer disease and/or patients without respond to traditional treatments);

- Melatonin with adenosine solubilized in water and stabilized with glycine for oncological treatment - technical preparation, effectivity and clinical findings;

- About Melatonin - In vitro, review and in vivo publications;

- 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;

- 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;

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

- 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;

- Neuroblastoma: Complete objective response to biological treatment;

- 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;

- Oesophageal squamocellular carcinoma: a complete and objective response;

- 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.