Neuroblastoma natural treatment research
October 1 2018 by
Ray Sahelian, M.D.

Neuroblastoma is the most common extracranial childhood cancer and the most common tumor occurring during infancy. Neuroblastoma is an embryonal malignancy of the sympathetic nervous system arising from neuroblasts. In the developing embryo, these cells invaginate, migrate along the neuraxis, and populate the sympathetic ganglia, adrenal gland medulla, and other sites. The pattern of distribution of these cells correlates with the sites of primary disease presentation.
   Neuroblastoma is the most common tumor in infants younger than 1 year of age; it accounts for 7-10% of childhood cancers.

Nutrients that have been looked at in relation to neuroblastoma treatment
As of 2018, I am not aware of human clinical studies regarding the use of natural supplements in the prevention or treatment of neuroblastoma. We hav no idea if the following herbs or nutrients would be clinically helpful. Discuss with your doctor before making any changes to your treatment regimen.

Β-carotene inhibits neuroblastoma tumorigenesis by regulating cell differentiation and cancer cell stemness. Biochem Biophys Res Commun. 2014.

Effect of Citrus bergamia juice on human neuroblastoma cells in vitro and in metastatic xenograft models. Neuroblastoma is the most common extracranial pediatric solid tumor with poor prognosis in children with disseminated stage of disease. A number of studies show that molecules largely distributed in commonly consumed fruits and vegetables may have anti-tumor activity. In this study we evaluate the effect of Citrus bergamia (bergamot) juice (BJ) in vitro and in a spontaneous metastatic neuroblastoma SCID mouse model. Qualitative and quantitative characterizations of BJ flavonoid fractions were performed by RP-HPLC/PDA/MS. We show that BJ significantly affects SK-N-SH and LAN-1 cell proliferation in vitro, but fails to reduce primary tumor weight in vivo. Moreover, BJ reduced cell adhesiveness and invasion of LAN-1 and SK-N-SH cells in vitro and the number of pulmonary metastases under consideration of the number of tumor cells in the blood in mice inoculated with LAN-1 cells in vivo. These effects without any apparent sign of systemic toxicity confirm the potential clinical interest of BJ and lay the basis for further investigation in cancer. Fitoterapia. 2014.

Zeaxanthin is a carotenoid that causes cell death or apoptosis in neuroblastoma cells. Whether this occurs if zeaxanthin is ingested as a supplement is difficult to predict.
The photoreceptor protector zeaxanthin induces cell death in neuroblastoma cells.
Anticancer Res. 2005.
The dietary carotenoid zeaxanthin protects against age-related eye disease by preventing apoptosis in photoreceptor cells. This study examined the effect of zeaxanthin on neuroblastoma cells in which apoptosis can be induced with lipid peroxidation products. Since zeaxanthin can inhibit lipid peroxidation and beta-carotene inhibits lipoxygenase (LOX) activity, it was of concern that zeaxanthin might inhibit apoptosis in these cancer cells. Apoptosis-resistant CHP100 neuroblastoma cells were treated with zeaxanthin. Apoptosis was assessed via an immunoassay for histone-associated DNA fragments and cytofluorimetric analysis of apoptotic body formation. The effect of zeaxanthin on the activity of two model LOXs and LOX-mediated lipid peroxidation in liposomes was assessed. Zeaxanthin strongly induced apoptosis in neuroblastoma cells. Consistent with this finding, zeaxanthin did not inhibit LOX activity.

Resveratrol has shown positive findings in rodents.

Curcumin has been studied in labs but I am not aware of human studies with curcumin as a treatment for neuroblastoma or in combination with traditional medical treatment.
In Vitro Cell Dev Biol Anim. 2018. Combined effects of curcumin and doxorubicin on cell death and cell migration of SH-SY5Y human neuroblastoma cells. The combination of curcumin augmented the anticancer activity of doxorubicin and significantly induced apoptosis. Curcumin suppresses growth and migration of SH-SY5Y cells and enhances the anticancer activity of doxorubicin. The addition of curcumin to therapeutic regimens may be promising for the treatment of neuroblastomas if a number of problems related to its in vivo bioavailability can be resolved. Graphical abstract ᅟ.

Resveratrol and neuroblastoma
Resveratrol -induced cellular apoptosis and cell cycle arrest in neuroblastoma cells and antitumor effects on neuroblastoma in mice.
Surgery. 2004. Department of Surgery, Far Eastern Memorial Hospital,, National Taiwan University College of Medicine, Taipei, Taiwan.
Resveratrol, a natural polyphenol, possesses chemopreventive and antitumor effects. We investigated the effects of resveratrol on the proliferation, apoptosis, and cell cycle alteration of neuroblastoma cells and determined its effects on neuroblastoma tumors in mice. Resveratrol caused significant cytotoxicity and increased apoptosis and S-phase accumulation of neuroblastoma cells. S-phase accumulation was related to the down-regulation of p21 and up-regulation of cyclin E. In addition, resveratrol exerted antitumor effects on neuroblastomas in mice. Thus, resveratrol shows promise for the treatment of neuroblastoma.

Curcumin, resveratrol and neuroblastoma
Curcumin and resveratrol induce apoptosis and nuclear translocation and activation of p53 in human neuroblastoma.
Anticancer Res. 2004. Department of Paediatric Laboratory Medicine, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.
Neuroblastoma is an aggressive childhood cancer of the peripheral nervous system arising from neural crest sympathoadrenal progenitor cells. Despite current rigorous treatment protocols, prognosis for high stage NB patients is poor and so there remains a need for more effective, less cytotoxic treatments. Curcumin and resveratrol possess anti-tumor properties in adult cancer models and negligible toxicity in normal cells, but little is known about the effect of these agents on pediatric cancers. Observations suggest that the cytotoxicity, cell cycle arrest and apoptosis induced by curcumin and resveratrol in neuroblastoma cells may be mediated via functionally activated p53 and merit further study.

Thymoquinone is a phytochemical compound found in the plant Nigella sativa.
Asian Pac J Cancer Prev. 2015. In Vitro Anti-Neuroblastoma Activity of Thymoquinone Against Neuro-2a Cells via Cell-cycle Arrest. We have recently shown that thymoquinone (TQ) has a potent cytotoxic effect and induces apoptosis via caspase-3 activation with down-regulation of XIAP in mouse neuroblastoma (Neuro-2a) cells. Interestingly, our results showed that TQ was significantly more cytotoxic towards Neuro-2a cells when compared with primary normal neuronal cells. In this study, the effects of TQ on cell-cycle regulation and the mechanisms that contribute to this effect were investigated using Neuro-2a cells. Cell-cycle analysis performed by flow cytometry revealed cell-cycle arrest at G2/M phase and a significant increase in the accumulation of TQ-treated cells at sub-G1 phase, indicating induction of apoptosis by the compound. Moreover, TQ increased the expression of p53, p21 mRNA and protein levels, whereas it decreased the protein expression of PCNA, cyclin B1 and Cdc2 in a dose- dependent manner. Our finding suggests that TQ could suppress cell growth and cell survival via arresting the cell-cycle in the G2/M phase and inducing apoptosis of neuroblastoma cells.

Neuroblastoma Survival
Children who survive cancer face a four-fold increased risk of developing cancers as adults, and these malignancies appear at an earlier-than-normal age, but careful screening -- as well as awareness of potential early symptoms -- can help ensure that disease is caught early, when it's much easier to treat. While childhood cancer survivors do face increased cancer risk, the vast majority of survivors do very well and will never have one of these outcomes. Patients with neuroblastoma are many times more likely to develop a second cancer, and have a more than 300-fold increased risk of kidney cancer. Hodgkin's lymphoma survivors were at more than four-fold increased risk of gastrointestinal cancer. Survivors of soft tissue sarcoma, neuroblastoma or leukemia are all at about a 20-fold increased risk of head and neck cancer. Two-thirds of patients who develop a second cancer have previously received radiation therapy to that part of the body, a known cancer risk. Intensified screening among childhood cancer survivors, such as colonoscopies to watch for gastrointestinal cancer and urine tests for kidney malignancy, can help identify disease at an early stage, when it is most curable. Patients can also be made aware of potential symptoms, such as swelling of lymph nodes or difficulty swallowing for head and neck cancer. Journal of Clinical Oncology, January 20, 2006.

Survival in children with neuroblastoma has improved over the last three decades, but the survivors remain at significant risk for a second malignancy. Journal of Clinical Oncology 2010.

Cyclooxygenases (COX) catalyse the conversion of arachidonic acid to prostaglandins. COX-2 is upregulated in several adult epithelial cancers. In neuroblastoma it has been shown that the majority of primary tumours and cell lines express high levels of COX-2, whereas normal adrenal medullas from children do not express COX-2. Treatment of neuroblastoma cells with nonsteroidal anti-inflammatory drugs (NSAIDs), inhibitors of COX, induces caspase-dependent apoptosis via the intrinsic mitochondrial pathway. Established neuroblastoma xenografts in nude rats treated with the dual COX-1/COX-2 inhibitor, diclofenac, or the COX-2 specific inhibitor, celecoxib significantly inhibits neuroblastoma growth in vivo. In vitro, arachidonic acid and diclofenac synergistically induces neuroblastoma cell death. This effect is further pronounced when lipoxygenases is inhibited simultaneously. Proton MR-spectroscopy (1H MRS) of neuroblastoma cells treated with COX-inhibitors demonstrates accumulation of polyunsaturated fatty acids and depletion of choline compounds. Thus, 1H MRS, which can be performed with clinical MR-scanners, is likely to provide pharmacodynamic markers of neuroblastoma response to COX-inhibition. Taken together, these data suggest the use of NSAIDs as a novel adjuvant therapy for children with neuroblastoma.

Loss of Caspase-8 makes neuroblastoma more aggressive
The caspase-8 gene plays a critical role in suppressing metastasis (spread) of neuroblastoma, and the expression of this gene is frequently absent in cancer cells that are aggressively metastasizing. In the absence of caspase-8 protein, the cell is significantly more capable of escaping from the primary tumor and spreading to other sites in the body. In laboratory studies that restoring the expression of the caspase-8 gene suppresses neuroblastoma metastases.

Neuroblastoma symptom
The most common symptoms of neuroblastoma are due to pressure from the tumor or bone pain from cancer that has spread to the bone and bone marrow. Protruding eyes and dark circles around the eyes are common neuroblastoma symptoms caused by the malignancy spread to the area behind the eye. This disease also may compress the spinal cord, leading to paralysis. Other neuroblastoma symptoms include anemian, fever, and hypertension.

Neuroblastoma in child
Neuroblastoma is the most common tumor in infants younger than 1 year of age; it accounts for 7-10% of childhood cancers. The most common sign of a neuroblastoma is an unusual lump or mass. These are usually found in the child's abdomen. The child may complain of abdominal fullness, discomfort, or pain, the direct result of a tumor being present. But the lump itself is usually not tender or sore to the touch. Masses can occur in other places such as the neck. Or the neuroblastoma can spread to the back of the eye, causing it to protrude.

Q. My son is a year old and he has neuroblastoma. Currently he is normal and acts like any kid at his age. He has not had any treatment yet with the hope that it is 4S stage and could go away by itself. Would you please help me provide any information regarding herbs, supplements, or natural therapy related to neuroblastoma in a child his age.
   A. We truly wish optimal healing for your child We can understand how difficult it must be for you as a parent. You may wish to ask his doctor to read this page regarding research with natural supplements and neuroblastoma. We don't have clinical experience treating neuroblastoma with herbs or supplements so we can't say how effective any of these supplements would be.

Q. I am writing to you for a friend whose 1 1/2 year-old child was diagnosed with neuroblastoma. Do you or know of anyone who works with neuroblastoma patients? I welcome any referrals and/or advice. I realize that you normally do not give out referrals (as stated on your site); however, I ask you to please provide a site or place to start some research.
   A. Sorry, I do not know of any doctor who works with neuroblastoma patients.

Neuroblastoma treatment
Treatment of neuroblastoma is determined by the stage of the disease at diagnosis and the child's age, site of the primary tumor and metastases, and tumor histology. Neuroblastoma has a more favorable prognosis if it is localized or the child is under one year old at diagnosis. Common treatment options include surgery, radiation therapy, chemotherapy and bone marrow transplantation.

Expert Opin Emerg Drugs. 2013. Emerging drugs for neuroblastoma. This accounts for 8 - 10% of pediatric cancers and is responsible for 15% of childhood cancer deaths. Despite multimodality treatment, the overall survival (OS) and event-free survival (EFS) in high-risk patients remain suboptimal. More than half of children diagnosed with high-risk neuroblastoma either do not respond to conventional therapies or relapse after treatment. New drugs and therapeutic strategies that are under development in clinical trials, which are currently recruiting patients.EXPERT OPINION:There is a need to improve the response rate of induction chemotherapy, which is not effective in a third of patients and also the other components of the current treatment, little efficacious in avoiding the relapses. Few drugs have been introduced as upfront therapy in the last years. Topotecan, irinotecan and temozolomide are expected to improve the response in high-risk neuroblastoma, but their impact on OS and EFS is unknown. Anti-GD2 antibodies combined with other immunomodulators (IL-2, GM-CSF) are an important advance in the treatment of these children. Nevertheless, the hope is put in the new drugs directed to molecular targets. Anti-angiogenic drugs, ALK antagonist and PI3K/Akt/mTOR inhibitors are among the most promising.