Vitamin E d-alpha-tocopheryl polyethylene glycol succinate (TPGS) provokes cell death in human neuroblastoma SK-N-SH cells via a pro-oxidant signaling mechanism

Abstract

Neuroblastoma (NB) is the most common neoplasm during infancy. Unfortunately, NB is still a lethal cancer.

Therefore, innovative curative therapies are immediately required.

In this study, we showed the pro-death activity of TPGS in human NB SK-N-SH cancer cells. NB cells were exposed to TPGS (10-80 μM).

We report for the first time that TPGS induces cell death by apoptosis in NB cells via a pro-oxidant-mediated signaling pathway.

Certainly, H2O2 directly oxidizes DJ-1 cysteine106-thiolate into DJ-1 cysteine106-sulfonate; indirectly activates the transcription factors NF-kappaB, P53 and c-JUN; induces up-regulation of mitochondria regulator proteins BAX/PUMA; provokes loss of mitochondrial membrane potential (ΔΨm) and activation of CASPASE-3/AIF, leading to nuclear disintegration, demonstrated by cellular and biochemical techniques such as fluorescence microscopy, flow cytometry and Western blot analysis.

Since TPGS is a U.S. Food and Drug Administration (FDA) -approved pharmaceutical excipient, this molecule might be used in clinical trials for NB treatment.

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See also:

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

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

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

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

- Neuroblastoma: Complete objective response to biological treatment;

- 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 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;

- 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;

- Oesophageal squamocellular carcinoma: a complete and objective response.