Botanical or Herbal Extracts
Berberine: Berberine is an alkaloid found in various different medicinal herbs. Probably the most popular herb containing berberine is Goldenseal (Hydrastis Canadensis), followed by Oregon grape (Berberis aquifolium) and Chinese Isatis (Isatis tinctoria).
A 1990 study tested the tumor-killing effect of berberine compared to the chemotherapy drug BCNU (carmustine) in both glioma cell cultures and in rodents implanted with tumors. Berberine alone produced a 91% kill rate in cell cultures, compared to 43% for BCNU. Combining berberine with BCNU yielded a kill rate of 97% (Zhang, RX et al 1990).
A 1994 paper described in vitro experiments using berberine alone, or in combination with laser treatments, on glioma cells. The combination was especially effective, suggesting “the possibility of berberine as a photosensitive agent” (Chen KT et al 1994).
A 2004 paper tells us that berberine increases the benefit of radiation treatment by making glioblastoma cells more sensitive to radiation damage, without affecting healthy brain cells (Wallace J et al 2004). A similar effect is seen in lung cancer wherein berberine sensitizes lung tumor cells to radiation (Peng PL et al 2008, Liu Y et al 2008).
Berberine slows the spread of nasopharyngeal carcinoma, decreasing motility of the tumor cells (Liu SJ et al 2008). Berberine inhibits gene expression and enzyme activity necessary for glioblastoma and astrocytoma growth (Wang DY et al 2002). It also inhibits an enzyme called arylamine N-acetyltransferase (NAT). NAT may initiate cancer and has been correlated with the carcinogenic effect of heterocyclic aromatic amines, the kind of chemicals formed when red meat is cooked (Hung CF et al 2000).
The scientific understanding of how berberine actually works continues to advance. A 2007 description suggested that berberine acts “through several ways, such as regulating apoptotic gene expression, suppressing the formation of tumor angiogenesis [and] blocking signal transduction pathway” (Yang J et al 2007). A 2008 study explained that berberine triggers apoptosis in glioblastoma cells through the mitochondrial caspases pathway (Eom KS et al 2008). As of 2009, research reported that berberine kills glioma cells through several mechanisms: “Cytotoxicity is attributable to apoptosis mainly through induced G2/M-arrested cells, in an ER-dependent manner, via a mitochondria-dependent caspase pathway regulated by Bax and Bcl-2” (Chen TC et al 2009). In 2010 explanations for action expanded to include the inhibition of NF-KappaB and the reduction of a series of chemicals that help cancer cells to survive, including one called survivin (Pazhang Y et al 2010). Survivin slows down apoptosis, allowing tumor cells to survive. Healthy cells do not produce survivin but cancer cells typically do (Pandey MK et al 2008).
Several hundred published papers suggest that berberine is effective against not only brain tumors but a range of cancers. In the last few months alone, several interesting papers have been published. Among their conclusions are: berberine prevents cell growth and induces apoptosis in breast cancer cells (Kim JB et al 2010; Patil JB et al 2010); berberine is cytotoxic to cervical cancer cells (Lu B et al 2010); berberine inhibits cell growth in pancreatic cancer cells by inducing DNA damage (Pinto-Garcia L et al 2010); and berberine triggers cellular suicide in tongue cancer (Ho YT et al 2009).
Although berberine has been studied in human clinical trials and shown to have several metabolic benefits, concerns about long-term use of berberine have been raised on the basis of certain preclinical studies (Kysenius 2014; Mikes 1985; Mikes 1983). Some evidence suggests that long-term berberine use, especially at high doses, may impair particular aspects of cellular metabolism in specific types of cells. The implications of this preclinical research are yet to be determined by long-term human clinical trials, therefore Life Extension currently recommends short-term use of berberine.
Boswellia: The resin from Boswellia serrata also has an important role in treating brain cancer. Boswellia is commonly used for treating inflammation because it acts as an NF-KappaB inhibitor. It is neuroprotective, anti-inflammatory, and reduces anxiety (Moussaieff A et al 2009).
One important use of boswellia is in the treatment of traumatic brain injuries. Boswellia decreases the brain swelling from glioblastoma, allowing a decrease in the use of prednisone and thus reducing its side effects (Janssen G et al 2000).
Boswellia inhibits hippocampal neurodegeneration and exerts a beneficial effect on functional outcome after closed head injury, as evidenced by reduced neurological severity scores and improved cognitive ability in an object recognition test (Moussaieff A et al 2008).
A 2006 paper reports that Boswellia serrata was gaining importance in the treatment of edema surrounding tumors and other chronic inflammatory diseases. This study suggested that boswellia might be considered as an alternative to corticosteroids in reducing cerebral peritumoral edema (Weber CC et al 2006).
Finding ways to reduce or replace steroid use in the treatment of brain tumors is important, since steroid drugs may protect brain tumor cells. According to a 2000 article in Neuroscience, “glucocorticoids are often used in the treatment of gliomas to relieve cerebral oedema, the inhibition of apoptosis by these compounds could potentially interfere with the efficacy of chemotherapeutic drugs.” (Gorman AM et al 2000)
A 2006 study reported that steroids interfere with glioma cell apoptosis (Ní Chonghaile T et al 2006). Steroids block the cancer-killing action of camptothecin, a chemotherapy drug used in treating glioma (Qian YH et al 2009).
Boswelliamay be doubly useful for primary brain tumors. Studies published in 2000 (Winking M et al 2000) and 2002 (Park YS et al 2002) tell us that in addition to helping reduce cerebral swelling around the tumor, boswellia also kills glioblastoma cells in a dose-dependent manner.
Boswellia is also useful for treating secondary brain tumors. In 2007 researchers reported using boswellia to treat a patient with breast cancer metastasis to the brain. Familiar with the German research on using boswellia in the treatment of primary brain tumors, the team tried it with these secondary brain tumors and reported benefit. After ten weeks of boswellia treatment in combination with radiation treatment, all signs of brain metastases on the patient’s CT scans had disappeared (Flavin DF 2007).
Curcumin: Curcumin is extracted from turmeric rhizomes (Curcuma longa), a plant that has been eaten for thousands of years. As of this writing, the National Institute of Health’s website, PubMed, lists 1,335 published papers on curcumin and cancer in the peer-reviewed scientific literature.
A growing number of these studies focus specifically on using curcumin in connection with brain cancer. A 2006 paper tells us curcumin suppresses growth of glioblastoma by triggering the apoptotic pathways that destroy glioblastoma cells (Karmakar S et al 2006). Curcumin turns off the signals in the cells that protect glioblastoma cells from apoptosis, allowing the suicide process to destroy the cancer cells (Karmakar S et al 2007, Luthra PM et al 2009).
Curcumin has a similar action against other brain tumor types, including meduloblastoma cells and pituitary cancers (Bangaru ML et al 2010, Elamin MH et al 2010). Curcumin inhibits pituitary cancer from forming (Schaaf C et al 2010). It also slows growth of pituitary tumors and inhibits production of excess pituitary hormones by tumors (Schaaf C et al 2009, Miller M et al 2008).
Curcumin’s mechanisms of action are complex. It acts through multiple pathways, interfering with cancer growth and stimulating cancer destruction (Choi BH et al 2008). Curcumin decreases Glial cell line-derived neurotrophic factor (GDNF), a chemical that promotes tumor migration and invasion (Lu DY et al 2010, Song H et al 2006). It also acts as an angiogenesis inhibitor (Perry MC et al 2010).
An article in Brain Research confirms that curcumin crosses the blood brain barrier; thus reaching the brain and any tumor cells there (Purkayastha S et al 2009).
A study published in the Journal of Neurochemistry reported that curcumin sensitized glioma cells to several of the chemotherapy drugs often utilized to treat brain cancers (cisplatin, etoposide, camptothecin, and doxorubicin) as well as to radiation. “These findings support a role for curcumin as an adjunct to traditional chemotherapy and radiation in the treatment of brain cancer” (Dhandapani KM et al 2007).
Curcumin has long been known for poor bioavilability, requiring high doses to achieve desired blood levels. A novel curcumin formulation, BCM-95®, has been developed. It delivers up to seven times more bioactive curcumin to the blood than earlier curcumin formulations. Human evidence for the increased bioavailability of BCM-95® was published in a 2008 study in the Indian Journal of Pharmaceutical Science (Antony B et al 2008). An earlier animal trial was published in Spice India in 2006 (Merina B et al 2006).
Other Natural Ingredients
Quercetin: Quercetin enhances glioma cell death (Siegelin MD et al 2009). While killing cancer cells, quercetin protects healthy brain cells (Braganhol E et al 2006).
An especially interesting study tested a combination of quercetin and the chemotherapy drug temozolomide (Temodar®) on astrocytoma tumor cells. Temozolomide is commonly used for the treatment of glioma in conjunction with radiation therapy. This drug typically kills brain tumor cells by triggering a process called autophagy, while quercetin promotes necrosis in a dose dependent manner. This study reported for the first time that quercetin combined with temozolomide was much more effective in inducing apoptosis, programmed cell death, in glioma cells than was either substance alone. To quote the authors, “Our results indicate that quercetin acts in synergy with temozolomide and when used in combination rather than in separate pharmacological application, both drugs are more effective in programmed cell death induction. Temozolomide administered with quercetin seems to be a potent and promising combination which might be useful in glioma therapy” (Jakubowicz-Gil J, et al 2010).
Resveratrol: Resveratrol also strongly inhibits brain tumor cells (Leone S et al 2008, Shao J et al 2009, Gagliano N et al 2010). Quercetin and resveratrol, when taken together “presented a strong synergism in inducing senescence-like growth arrest. These results suggest that combining these polyphenols can potentiate their antitumoral activity, thereby reducing the therapeutic concentration needed for glioma treatment” (Zamin LL et al 2009).
Green Tea and Coffee: People who drink five cups per day of tea or coffee are 40% less likely to get glioma (Holick CN et al 2010).
A 2006 study informed us that the EGCG in green tea reduces the radio-resistance of glioblastoma cells potentially increasing the benefit of the standard radiation and chemotherapy treatment of this cancer (Karmakar S et al 2006).
Caffeine, found in significant quantities in coffee and green tea, inhibits migration of glioblastoma cells and increases survival (Kang SS et al 2010). It also makes glioma cells more sensitive to ionizing radiation and chemotherapy (Sinn B et al 2010). Caffeine enhances the effect of temozolomide in radiation treatments (Chalmers AJ et al 2009).
At least part of the explanation for these benefits is that coffee is a peroxisome proliferator-activated receptor (PPAR) gamma agonist (Choi SY et al 2007). PPAR gamma agonists inhibit brain tumor growth and possibly even brain cancer stem cells (Grommes C et al 2010, Chearwae W 2008).
Sulforaphane: Sulforaphane is one of the active compounds in cruciferous vegetables, especially broccoli, responsible for their anti-cancer action. It has been shown to confer neuroprotection and preserve blood-brain-barrier integrity in animal models (Dash PK et al 2009).
Sulforaphane activates “multiple molecular mechanisms for apoptosis in glioblastoma cells following treatment” (Karmakar S et al 2006).
Resveratrol and sulforaphane act synergistically against brain tumor cells. A 2010 article states, “Combination treatment with resveratrol and sulforaphane inhibits cell proliferation and migration, and reduces cell viability. Resveratrol and sulforaphane, may be a viable approach for the treatment of glioma.” (Jiang H et al 2010)