Curcumin’s Beneficial Effects on Neuroblastoma: Mechanisms, Challenges, and Potential Solutions

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.

Elucidating Role of Reactive Oxygen Species (ROS) in Cisplatin Chemotherapy: A Focus on Molecular Pathways and Possible Therapeutic Strategies

“…In the section, we provide a mechanistic discussion around using these compounds and their signaling targets. Plant derived-natural compounds have opened a new gate in cancer therapy due to their multitargeting capacity [193][194][195][196]. Melatonin is a hormone of pineal gland that is synthesized in other organs with higher concentrations [197].…”

Natural Compounds in Glioblastoma Therapy: Preclinical Insights, Mechanistic Pathways, and Outlook

“…Chemically, curcuminoids are diarylheptanoids, which have a seven carbon chain connecting two substituted aromatic rings. These polyphenols decrease proliferation and induce apoptosis, cell cycle arrest, and mitochondrial dysfunction in cancers of the nervous system [ 21 ]. They also notably modulate tumor angiogenesis and inflammation [ 22 ].…”

“…BBR, for instance, has low oral bioavailability due to its poor absorption and rapid first-pass metabolism [ 77 ]. Osthole and curcumin are similarly constrained [ 21 , 78 , 79 ]. Furthermore, the flavonoids quercetin, naringin, and EGCG exhibit low oral bioavailability due to metabolic alterations and their high molecular weights [ 80 ].…”

“…As such, numerous formulations were developed to enhance these properties of natural substances. For instance, protein complexes, microemulsions, nanosuspensions, and nanoparticles increase the bioavailability, absorption, and brain uptake of curcumin [ 21 ]. In particular, dodecamer peptide-functionalized polydopamine-coated curcumin-loaded zein nanoparticles effectively cross the BBB and deliver curcumin to GBM cells, with high penetration into 3D tumor spheroids.…”

Curcumin–Coumarin Hybrid Analogues as Multitarget Agents in Neurodegenerative Disorders

“…Approximately 40 µM concentration and 24 h exposure are the critical parameters at which the cell viability significantly decreases [ 30 ]. Other authors describe even lower concentrations (10 µM) to decreases SH-SY5Y proliferation and 20 µM to cause apoptosis [ 31 ]. Considering the controversies found in the literature, we studied the neuroprotective effects of low concentrations (≤10 µM) of curcumin and curcumin–coumarin hybrid analogues on two different neuronal models, primary culture of rat motor cortex neurons and SH-SY5Y cell line.…”