Abstract

Curcumin, a natural polyphenolic compound derived from the South Asian turmeric plant (Curcuma longa), has well-characterized antioxidant, anti-inflammatory, anti-protein-aggregate, and anticancer properties. Neuroblastoma (NB) is a cancer of the nervous system that arises primarily in pediatric patients. In order to reduce the multiple disadvantages and side effects of conventional oncologic modalities and to potentially overcome cancer drug resistance, natural substances such as curcumin are examined as complementary and supportive therapies against NB. In NB cell lines, curcumin by itself promotes apoptosis and cell cycle arrest through the suppression of serine–threonine kinase Akt and nuclear factor kappa of activated B-cells (NF-κB) signaling, induction of mitochondrial dysfunction, and upregulation of p53 and caspase signaling. While curcumin demonstrates anti-NB efficacy in vitro, cross-validation between NB cell types is currently lacking for many of its specific mechanistic activities. Furthermore, curcumin’s low bioavailability by oral administration, poor absorption, and relative insolubility in water pose challenges to its clinical introduction. Numerous curcumin formulations, including nanoparticles, nanocarriers, and microemulsions, have been developed, with these having some success in the treatment of NB. In the future, standardization and further basic and preclinical trials will be required to ensure the safety of curcumin formulations. While the administration of curcumin is clinically safe even at high doses, clinical trials are necessary to substantiate the practical efficacy of curcumin in the prevention and treatment of NB.

Highlights

  • Neuroblastoma (NB) is a solid pediatric tumor of the nervous system that arises from neural progenitor cells

  • Mitochondrial dysfunction leads to the release of cytochrome c, as observed in SK-N-SH cells treated with doxorubicin and B50 cells treated with cisplatin [94,96]

  • Epigenetic modifications that occur during tumor progression are potentially reversible, with consequent diminishment of the Warburg effect [118,119]. These results suggest that the Warburg effect, in which decreased vascularization, nutrient deprivation, and hypoxia lead to a tumor microenvironment with low pH, is a reversible process that may be targeted by curcumin

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Summary

Natural Substances in the Prevention and Treatment of Neuroblastoma

Neuroblastoma (NB) is a solid pediatric tumor of the nervous system that arises from neural progenitor cells. A treatment regimen for high-risk NB could include the following: (1) induction chemotherapy with cisplatin, carboplatin, etoposide, vincristine, and cyclophosphamide; (2) surgical removal of the primary tumor, with or without additional topotecan, vincristine, and doxorubicin therapy; (3) consolidation chemotherapy utilizing busulfan and melphalan, or carboplatin, etoposide, and melphalan; (4) stem cell rescue; (5) radiation therapy; and (6) maintenance chemotherapy, with or without immunotherapy [11]. These often complex and multifaceted conventional treatment regimens are clinically trialed and effective. P53-dependent cell death in various tumor cells can be and effectively activated by treatment with the naturally occurring polyphenol curcumin [41]

Structure and Biological Properties of Curcumin
Rationale and Aims of the Study
Study Methodology
Curcumin as an Anticancer Agent in NB
Apoptosis and Cell Cycle Arrest
Effects on NB Cell Migration and Glucose Metabolism
Curcumin Applied Simultaneously with Other Natural Substances
Curcumin Applied Simultaneously with Conventional Chemotherapeutics
Curcumin in Conjunction with Radiation Therapy
Challenges in the Use of Curcumin in the Prevention and Treatment of NB
Novel Curcumin Encapsulation and Delivery Modalities
Curcumin–Protein Complexes
Curcumin Microemulsions
Curcumin Nanosuspensions
Curcumin Nanoparticles
Cell Uptake and Anti-NB Efficacy of Curcumin Formulations
Patterns in NB Cell Line Usage in Curcumin Studies
Apoptotic Mechanisms
Synergistic Effects
Curcumin Formulations
Repetition of Mechanistic Trials and Synergistic Studies Across NB Cell Lines
Further Testing and Standardization of Curcumin Formulations
Investigation of the Effects of Curcumin on NB Cell Metabolism
Investigation of the Effects of Curcumin on NB Drug Resistance
Clinical Trials of Curcumin in NB
Findings
10. Conclusions and Outlook
Full Text
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