Berberine as a cancer treatment

Berberine as a cancer treatment

Berberine has been shown in research to have a number of quite separate pathways against cancer (writes former Oxford University Biochemist, Chris Woollams).

The many benefits of Berberine

Berberine is an isoquinoline alkaloid component of many medicinal herbs, such as Goldenseal (Hydrastis Canadensis), Chinese Isatis (Isatis tinctoria), Oregan grape root (Berberis aquifolium) and berberry bark.  

It has anti-inflammatory benefits through its ability to inhibit Cox-2 expression. Several studies show this attribute in vitro and in vivo (for example 1, 2). This is one of the major reasons behind its inhibitory benefits against cancer.

It also has anti-infectious benefits. For example, against the recurrence of Clostridium difficile(3), and it has also been shown to attack the membrane of Candida albicans(4) - common yeast.

Berberine can act on its own, but can also improve effectiveness of chemotherapy by enhancing chemrsensitivity(5) and it improves radiotherapy by enhancing radio sensitisation of cancer cells(6). It overcomes cancer cell resistance.

It truly has multiple actions. Only a small part of its benefit seems to be its effect in lowering blood glucose - it reduces glucose production in the liver and performs as well as metformin, the type-2 diabetes drug (see here). In fact, Berberine is as powerful as both the pharmaceutical drugs, metformin and glibenclamide. It has also been used in weight loss programmes.

Expert Herbalist, Alan Hopking, once described Berberine in our 2005 article thus: 

"Berberine has an action against some pathogens that is actually stronger that that of antibiotics commonly used. It has been found to inhibit candida albicans and prevents the overgrowth of yeasts, a common side effect of antibiotic use.

This fascinating alkaloid increases blood supply to the spleen and thus increases immune response

It has also been shown to activate macrophages in a number of ways. Coupled with its ability to inhibit tumour formation, it seems Berberine possesses some anti-neoplasic activity."

Since that time, research studies have gathered apace. Berberine is known to reduce blood sugar levels. This action appears to be completely independent of insulin. Its hypoglycaemic effect is caused by its inhibition of mitochondrial activity and the stimulation of the AMPK pathway(7). These actions make it useful in diabetes and cancer treatments.

Berberine and cancer

Berberine has a number of important actions against cancer. Not least its ability to reduce blood sugar levels. For example, it possesses strong anti-inflammatory actions against Cox-2. And, it has a number of strong digestive benefits. Combined these give it a strong influence in colorectal cancer where it can limit invasion and metastases(8).

Crucially, it changes the way cells metabolise their fuel - it works on the ’metabolic master switch’, an enzyme inside all cells called AMP-activated protein kinase, or AMPK, which is involved in a great many biochemical pathways. In cancer cells there is a marked decline in this enzyme. Berberine seems to preserve the integrity of the enzyme and even turn it back on, encouraging the re-start of normal aerobic mitochondrial activity.

There are over 500 quality research studies conducted on Berberine and cancer and research is gathering momentum. For example:

 * A 2016 study on breast cancer cells showed that berberine and curcumin worked in combination to cause apoptosis (cancer cell death) and autophagic cell death(9).

 *  A 2017 study showed that Berberine could inhibit the metastases and invasion of colorectal cancer cells both in vivo and in vitro in three ways - by restricting Cox-2, by reducing phosphorylation and by restricting MMP expression(10).

 * A 2015 study showed that it aided the action of temozolomide against glioma (brain cancer).  Indeed part of the study suggested it was also effective in its own right.

Go To: Berberine has a strong effect against brain cancer

 * This is not the first time it has shown effect with brain tumours. One study showed it might be a useful adjunct in PDT - in vitro experiments showed using berberine alone, or in combination with laser treatments, on glioma cells were both effective (Chen KT et al, 1994).

 * In 2004 it was shown to be a sensitizer of glioma cells where it increased the success of radiotherapy in brain tumours (Wallace J et al, 2004).

 * Berberine sensitizes lung tumor cells to radiation (Peng PL et al 2008, Liu Y et al, 2008).

 * Berberine prevents cell growth and induces apoptosis in breast cancer cells (Kim JB et al 2010; Patil JB et al, 2010); In 2016, a study by Lanzhou University Medical School in China showed that because Berberine could turn the AMPK enzyme back on, Berberine could correct breast cancer cells.

 * 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).

 * Berberine triggers cellular suicide in tongue cancer (Ho YT et al 2009).

 * Berberine enhanced the activity of carmustine, a chemo drug often used on brain tumours. Berberine in culture or in rats given cancer tumours, on its own produced a 91% kill rate in cell cultures, compared to 43% for carmustine. When the two were combined the kill rate rose to 97% (Zhang, RX et al, 1990).

In 2011, a review of the anti-cancer effects of berberine concluded that it was a promising, safe anti-tumour agent with a number of potential therapeutic uses(11).

Other ways Berberine works against cancer?

Berberine seems to work in other ways too:

1. It inhibits gene expression and enzyme activity necessary for glioblastoma and astrocytoma growth (Wang DY et al, 2002).

2. It also inhibits an enzyme called arylamine N-acetyltransferase (NAT) that is thought to initiate cancer (Hung CF et al, 2000).

3. In 2007 there were conclusions 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).

4. A 2008 study explained that berberine triggers apoptosis in glioblastoma cells through the mitochondrial caspases pathway (Eom KS et al 2008).

5. In 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).

6. In 2010 showed that Berberine could inhibit NF-KappaB and other compounds that help cancer cells survive by slowing apoptosis (Pazhang Y et al 2010).

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Metformin and Berberine against cancer

Berberine seems to have so many benefits against cancer, well beyond its sugar control. But Metformin also has sugar controlling benefits and acts on AMPK - it is the ’diabetes drug’. For this reason, many users take an either/or approach. That seems to be quite wrong. Actually Berberine and Metformin seem to enhance each other’s activity. For example, there is a study with Non-Small Cell Lung Cancer (NSCLC) showing exactly that (12). They work together in vitro and in vivo against a particularly nasty cancer.

Warnings

Berberine is as powerful as pharmaceutical drugs. There are concerns about long-term usage causing metabolic changes. More work is however needed on this but warnings over long-term use persist.

References

1. http://iv.iiarjournals.org/content/19/1/247.abstract

2. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0069240

3. https://aac.asm.org/content/59/7/3726

4. https://bmccomplementalternmed.biomedcentral.com/articles/10.1186/s12906-017-1773-5

5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535724/

6. https://www.spandidos-publications.com/ijmm/30/5/1166/download

7. https://www.sciencedirect.com/science/article/pii/S2211383512000871

8. https://www.ncbi.nlm.nih.gov/pubmed/25954974

9. Kai Wang et al: 7 Jan 2016; Nature, Scientific reports 26064

10. Xuan Liu, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4425560/

11. A promising anti-tumour agent

12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5742731/

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