Berberine Benefits for Breast Cancer

There are at present just under 6300 studies on berberine benefits. Researchers have been examining berberine for a number of years, with the bulk of studies being done in the last ten years. Berberine has a multitude of pharmacological actions and some very real benefits for breast cancer and, in this article, I’m going to tell you what they are!

What is Berberine?

Berberine is a botanical extract – a phytochemical – derived from a number of different plants, specifically the European Barberry (Berberis vulgaris), Oregon Grape (Berberis aquifolium), Tree Turmeric (Berberis aristata), Goldenseal (Hydrastis canadensis), Chinese goldthread (Coptis chinensis), Mexican Prickly Poppy (Argemone mexicana), Baikal skullcap root (Scutellaria baicalensis), and Greater Celandine (Chelidonium majus). Two other botanicals containing berberine will be familiar to Chinese medicine practitioners: Chinese cork tree (Phellodendron chinensis), and Amur cork tree (Phellodendron amurense) aka huáng bò.

Berberine has a rich, yellow hue and has been used for centuries as a natural fabric dye. It is an alkaloid, which is a class of nitrogenous organic compounds.

Berberine has been used for centuries in traditional Chinese medicine (TCM), Ayurvedic medicine, and in Western herbalism to treat digestive complaints, infections, as an anti-inflammatory and for high cholesterol and blood sugar disorders. Herbalists especially value plants containing berberine because it works so well against certain pathogens – even better than some antibiotics. It has been found to inhibit candida albicans and it also prevents yeast overgrowth (a common side effect of antibiotics). [1] [2]

We now know, through an amazing and ever-growing collection of scientific studies that berberine is also a potent anticancer phytochemical.

Berberine and AMPK

One of the most interesting things about berberine is that it alters the way cells utilize fuel. It works on an enzyme inside of all cells known as AMPK (adenosine monophosphate-activated protein kinase). To understand how berberine works, we first need to understand AMPK. This enzyme acts like an energy regulatory control switch. It regulates how energy is produced and utilized in the body. AMPK starts a cascade of events within the cell that is all about maintaining energy homeostasis, so it’s very important. AMPK senses when cellular energy is low, and switches cellular metabolism from ATP-consuming pathways to ATP-producing pathways. I hope that makes sense. But suffice to say that the AMPK system is involved in MANY biological activities and pathways that normalize glucose, lipid, and energy imbalances.

In cancer cells particularly, it is noted that there is a deficiency of AMPK. Berberine works to improve the activity of AMPK – indeed, it activates AMPK – which in turn promotes the normal aerobic activity of the cell’s mitochondria. Berberine is one of the few phytochemicals that can do this. [3] [4]

As a result of its interaction with AMPK, berberine reduces blood sugar levels, and this action has nothing to do with insulin, but rather its stimulation of the AMPK enzyme pathway. Berberine has been shown to work as well as metformin, the leading type-2 diabetes drug. [5] More on that below.

Berberine and NF-kappa B

Berberine also inhibits a protein known as NF-kappa B which acts as a strong promoter of inflammation in cells. Cancer cells frequently have a permanently activated NF-kappa B, according to integrative oncologist Dr Brian Lawenda. This keeps the cells in rapid growth mode, prevents them from dying and promotes inflammation, which we know leads to cancer growth. [6] [7]

The Research on Berberine and Cancer

We have a number of studies that indicate berberine has all of these benefits for breast cancer, and there are 14 of them!

1. Berberine inhibits cell proliferation (rapid growth) by inducing cell cycle arrest and promoting apoptosis (planned cell death) in both estrogen receptor positive (ER+) and negative (ER-) breast cancer cells [8] thru [21]

2. Berberine reduces tumor volume and weight [22]

3. Berberine reduces inflammation [23] thru [26]

4. Berberine inhibits the ability of tumor cells to migrate and invade other areas of the body [27] thru [33]

5. Berberine inhibits angiogenesis – the ability of a developing tumor to create new blood vessels to supply itself [34] [35]

6. Berberine down-regulates (inhibits) the expression of genes associated with breast cancer promotion like MAPK, PI3K, Akt, mTOR, STAT3, Nrf2, COX-2, Bcl-2, AMPK, EGFR, NF-kB [36] thru [45]

7. Berberine up-regulates (promotes) tumor suppressor genes like P27, P53 [46] thru [50]

8. Berberine works synergistically with chemotherapy drugs like doxorubicin and tamoxifen by sensitizing cancer cells. Furthermore it has chemoprotective properties, which means it protects the heart, liver, lungs, and kidneys from damage caused by these therapies [51] thru [55]

9. Berberine amplifies the effects of radiotherapy [56] [57]

10. Berberine inhibits tendency of cancer cells to become drug resistant over time [58] [59]

11. Berberine targets cancer stem cells [60]

12. Berberine suppresses HER2-overexpressing cancer cells [61] [62], and reverses resistance of HER2+ cells to the targeted drug Tykerb / Lapatinib [63]

13. Berberine has immunomodulatory effects, meaning it has the ability to modulate the function of the immune system. If immunity is low, berberine acts to boost it. If immunity is already over-reacting, berberine has the ability to dampen it. [64]

14. Last, but certainly not least, in animal studies, berberine improves glucose tolerance and reduces the incidence of metabolic syndrome, which we know is a risk factor for breast cancer. [65] [66] For more information see my article Healthy Strategies to Avoid Insulin Resistance, Metabolic Syndrome – https://marnieclark.com/healthy-strategies-to-avoid-insulin-resistance-metabolic-syndrome/

Combining Berberine with Curcumin

A 2016 study [67] found that curcumin combined with berberine reduced the growth of both ER+ and ER- breast cancer cells, and worked better together than either one of them on its own.

Berberine and Metformin

Some integrative oncologists and forward-thinking conventional oncologists have been using the anti-diabetes drug metformin with their breast cancer patients because it reduces blood sugar, has an effect on the AMPK pathway, and has a positive effect on tumors. However, one 2018 paper [68] (and there are others) revealed that berberine does eveything that metformin does. Without the side effects.

Additional Bonus – Reduces High Cholesterol

A number of studies have shown that berberine also reduces blood lipids by a significant degree, which is good news for breast cancer survivors with high cholesterol readings. [69] [70]

Berberine Dosage

One 2020 study [71] indicated that low doses of berberine may be ineffective or even carcinogenic. So knowing how to properly take berberine is important.

According to Jacob Schor, ND in his paper “Clinical Applications for Berberine” [72], “…berberine actually appears to be well absorbed. The confusion lies in the fact that it is quickly metabolized. Blood clearance is so fast and biotransformation in the liver so rapid that berberine disappears from the blood faster than it can be measured. Berberine metabolites may be responsible for berberine’s biological action. Most berberine is metabolized in the liver through phase I demethylation and phase II glucuronidation, after which the metabolites are excreted with the bile. Considerable interest has been directed toward creating nanoparticle delivery systems for berberine, the assumption being that therapeutic effects will increase with increased absorption. These delivery systems fall into 3 general types: solid lipid nanoparticles, nanoemulsions, and liposomes.”

Berberine has a good track record of being safe, but be sure to see the warning below. The recommended dosage of berberine is between 1,000-1,500 mg per day taken in divided doses over the day (ie one 500 mg capsule with each meal) because of the quick blood clearance factor.

Warning – Possible Herb-Drug Interactions

Because berberine does inhibit a group of liver enzymes known as cytochrome P450 (specifically CYP2D6, CYP2C9 and CYP3A4), it is not recommended to take a drug or supplement together that also inhibits these enzymes – doing so can increase the blood levels of both compounds, thus increasing the risk of toxicity. Always discuss your use of berberine with your chosen health professional first before starting on this.

Research:

[1] Berberine Antifungal Activity in Fluconazole-Resistant Pathogenic Yeasts: Action Mechanism Evaluated by Flow Cytometry and Biofilm Growth Inhibition in Candida spp. – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879420/
[2] Membrane of Candida albicans as a target of berberine – https://bmccomplementalternmed.biomedcentral.com/articles/10.1186/s12906-017-1773-5
[3] Effects and mechanisms of berberine in diabetes treatment –
https://www.sciencedirect.com/science/article/pii/S2211383512000871
[4] Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states – https://pubmed.ncbi.nlm.nih.gov/16873688/
[5] Berberine in the Treatment of Type 2 Diabetes Mellitus: A Systemic Review and Meta-Analysis – https://www.hindawi.com/journals/ecam/2012/591654/
[6] Berberine alleviates oxidized low-density lipoprotein-induced macrophage activation by downregulating galectin-3 via the NF-kB and AMPK signaling pathways – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587449/
[7] Berberine inhibits human gastric cancer cell growth via deactivation of p38/JNK pathway, induction of mitochondrial-mediated apoptosis, caspase activation and NF-?B inhibition – https://pubmed.ncbi.nlm.nih.gov/32277648/
[8] Berberine Inhibits Growth of the Breast Cancer Cell Lines MCF-7 and MDA-MB-231 – https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-2007-993779
[9] A systematic review of the anticancer properties of berberine, a natural product from Chinese herbs – http://www.medicinacomplementar.com.br/biblioteca/pdfs/Cancer/ca-2013.pdf
[10] Berberine induces apoptosis in breast cancer cells (MCF-7) through mitochondrial-dependent pathway – https://pubmed.ncbi.nlm.nih.gov/20691179/
[11] Antitumor effect of novel berberine derivatives in breast cancer cells – https://pubmed.ncbi.nlm.nih.gov/24000115/
[12] Berberine-Induced Apoptosis in Human Breast Cancer Cells is Mediated by Reactive Oxygen Species Generation and Mitochondrial-Related Apoptotic Pathway – https://scholarcommons.sc.edu/biol_facpub/242/
[13] Berberine enhances the anti-tumor activity of tamoxifen in drug-sensitive MCF-7 and drug-resistant MCF-7/TAM cells – https://www.spandidos-publications.com/10.3892/mmr.2016.5490?text=abstract
[14] Berberine Enhances Chemosensitivity and Induces Apoptosis Through Dose-orchestrated AMPK Signaling in Breast Cancer – https://www.jcancer.org/v08p1679
[15] Berberine and Evodiamine Act Synergistically Against Human Breast Cancer MCF-7 Cells by Inducing Cell Cycle Arrest and Apoptosis – https://ar.iiarjournals.org/content/37/11/6141.full
[16] Berberine Inhibits Proliferative Ability of Breast Cancer Cells by Reducing Metadherin – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900918/
[17] Anticancer effect of berberine based on experimental animal models of various cancers: a systematic review and meta-analysis – https://bmccancer.biomedcentral.com/articles/10.1186/s12885-019-5791-1
[18] The Anti-Cancer Mechanisms of Berberine: A Review – https://www.dovepress.com/the-anti-cancer-mechanisms-of-berberine-a-review-peer-reviewed-fulltext-article-CMAR
[19] Effects of Berberine and Its Derivatives on Cancer: A Systems Pharmacology Review – https://www.frontiersin.org/articles/10.3389/fphar.2019.01461/full
[20] Berberine Inhibits the Expression of SCT through miR-214-3p Stimulation in Breast Cancer Cells – https://www.hindawi.com/journals/ecam/2020/2817147/
[21] Berberine and Emodin abrogates breast cancer growth and facilitates apoptosis through inactivation of SIK3-induced mTOR and Akt signaling pathway – https://www.sciencedirect.com/science/article/abs/pii/S0925443920302453
[22] Anticancer effect of berberine based on experimental animal models of various cancers: a systematic review and meta-analysis – https://bmccancer.biomedcentral.com/articles/10.1186/s12885-019-5791-1
[23] Berberine suppresses proinflammatory responses through AMPK activation in macrophages – https://pubmed.ncbi.nlm.nih.gov/19208854/
[24] Anticancer effect of berberine based on experimental animal models of various cancers: a systematic review and meta-analysis – https://bmccancer.biomedcentral.com/articles/10.1186/s12885-019-5791-1
[25] The Anti-Cancer Mechanisms of Berberine: A Review – https://www.dovepress.com/the-anti-cancer-mechanisms-of-berberine-a-review-peer-reviewed-fulltext-article-CMAR
[26] Effects of Berberine and Its Derivatives on Cancer: A Systems Pharmacology Review – https://www.frontiersin.org/articles/10.3389/fphar.2019.01461/full
[27] A systematic review of the anticancer properties of berberine, a natural product from Chinese herbs – http://www.medicinacomplementar.com.br/biblioteca/pdfs/Cancer/ca-2013.pdf
[28] Berberine suppresses migration of MCF-7 breast cancer cells through down-regulation of chemokine receptors – https://www.scienceopen.com/document?vid=d05f13ac-a1f0-4ea9-834e-e8633169f4ce
[29] Berberine Suppresses Cell Motility Through Downregulation of TGF-ß1 in Triple Negative Breast Cancer Cells – https://www.karger.com/Article/Fulltext/487171
[30] Anticancer effect of berberine based on experimental animal models of various cancers: a systematic review and meta-analysis – https://bmccancer.biomedcentral.com/articles/10.1186/s12885-019-5791-1
[31] The Anti-Cancer Mechanisms of Berberine: A Review – https://www.dovepress.com/the-anti-cancer-mechanisms-of-berberine-a-review-peer-reviewed-fulltext-article-CMAR
[32] Effects of Berberine and Its Derivatives on Cancer: A Systems Pharmacology Review – https://www.frontiersin.org/articles/10.3389/fphar.2019.01461/full
[33] Berberine Inhibits the Expression of SCT through miR-214-3p Stimulation in Breast Cancer Cells – https://www.hindawi.com/journals/ecam/2020/2817147/
[34] Anticancer effect of berberine based on experimental animal models of various cancers: a systematic review and meta-analysis – https://bmccancer.biomedcentral.com/articles/10.1186/s12885-019-5791-1
[35] Effects of Berberine and Its Derivatives on Cancer: A Systems Pharmacology Review – https://www.frontiersin.org/articles/10.3389/fphar.2019.01461/full
[36] A systematic review of the anticancer properties of berberine, a natural product from Chinese herbs – http://www.medicinacomplementar.com.br/biblioteca/pdfs/Cancer/ca-2013.pdf
[37] Berberine-Induced Apoptosis in Human Breast Cancer Cells is Mediated by Reactive Oxygen Species Generation and Mitochondrial-Related Apoptotic Pathway – https://scholarcommons.sc.edu/biol_facpub/242/
[38] Berberine enhances the anti-tumor activity of tamoxifen in drug-sensitive MCF-7 and drug-resistant MCF-7/TAM cells – https://www.spandidos-publications.com/10.3892/mmr.2016.5490?text=abstract
[39] Berberine Enhances Chemosensitivity and Induces Apoptosis Through Dose-orchestrated AMPK Signaling in Breast Cancer – https://www.jcancer.org/v08p1679
[40] Berberine Reverses Hypoxia-induced Chemoresistance in Breast Cancer through the Inhibition of AMPK- HIF-1a – https://www.ijbs.com/v13p0794.htm
[41] Berberine Suppresses Cell Motility Through Downregulation of TGF-ß1 in Triple Negative Breast Cancer Cells – https://www.karger.com/Article/Fulltext/487171
[42] Antitumor effects of berberine against EGFR, ERK1/2, P38 and AKT in MDA-MB231 and MCF-7 breast cancer cells using molecular modelling and in vitro study – https://link.springer.com/article/10.1016/j.pharep.2018.07.005
[43] The Anti-Cancer Mechanisms of Berberine: A Review – https://www.dovepress.com/the-anti-cancer-mechanisms-of-berberine-a-review-peer-reviewed-fulltext-article-CMAR
[44] Effects of Berberine and Its Derivatives on Cancer: A Systems Pharmacology Review – https://www.frontiersin.org/articles/10.3389/fphar.2019.01461/full
[45] Berberine and Emodin abrogates breast cancer growth and facilitates apoptosis through inactivation of SIK3-induced mTOR and Akt signaling pathway – https://www.sciencedirect.com/science/article/abs/pii/S0925443920302453
[46] Berberine induces apoptosis in breast cancer cells (MCF-7) through mitochondrial-dependent pathway – https://pubmed.ncbi.nlm.nih.gov/20691179/
[47] Antitumor effect of novel berberine derivatives in breast cancer cells – https://pubmed.ncbi.nlm.nih.gov/24000115/
[48] Berberine enhances the anti-tumor activity of tamoxifen in drug-sensitive MCF-7 and drug-resistant MCF-7/TAM cells – https://www.spandidos-publications.com/10.3892/mmr.2016.5490?text=abstract
[49] Effects of Berberine and Its Derivatives on Cancer: A Systems Pharmacology Review – https://www.frontiersin.org/articles/10.3389/fphar.2019.01461/full
[50] Berberine Inhibits the Expression of SCT through miR-214-3p Stimulation in Breast Cancer Cells – https://www.hindawi.com/journals/ecam/2020/2817147/
[51] Berberine-A potent chemosensitizer and chemoprotector to conventional cancer therapies – https://pubmed.ncbi.nlm.nih.gov/33559280/
[52] Effects of berberine on proliferation, cell cycle distribution and apoptosis of human breast cancer T47D and MCF7 cell lines – https://ijbms.mums.ac.ir/article_4281.html
[53] Berberine enhances the anti-tumor activity of tamoxifen in drug-sensitive MCF-7 and drug-resistant MCF-7/TAM cells – https://www.spandidos-publications.com/10.3892/mmr.2016.5490?text=abstract
[54] Berberine Enhances Chemosensitivity and Induces Apoptosis Through Dose-orchestrated AMPK Signaling in Breast Cancer – https://www.jcancer.org/v08p1679
[55] Berberine Reverses Hypoxia-induced Chemoresistance in Breast Cancer through the Inhibition of AMPK- HIF-1a – https://www.ijbs.com/v13p0794.htm
[56] Berberine-A potent chemosensitizer and chemoprotector to conventional cancer therapies – https://pubmed.ncbi.nlm.nih.gov/33559280/
[57] Berberine can amplify cytotoxic effect of radiotherapy by targeting cancer stem cells – https://www.futuremedicine.com/doi/10.2217/bmt-2020-0007
[58] Berberine Improves Chemo-Sensitivity to Cisplatin by Enhancing Cell Apoptosis and Repressing PI3K/AKT/mTOR Signaling Pathway in Gastric Cancer – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756080/
[59] A systematic review of the anticancer properties of berberine, a natural product from Chinese herbs – http://www.medicinacomplementar.com.br/biblioteca/pdfs/Cancer/ca-2013.pdf
[60] Berberine can amplify cytotoxic effect of radiotherapy by targeting cancer stem cells – https://www.futuremedicine.com/doi/10.2217/bmt-2020-0007
[61] Growth Suppression of HER2-Overexpressing Breast Cancer Cells by Berberine via Modulation of the HER2/PI3K/Akt Signaling Pathway – https://pubs.acs.org/doi/10.1021/jf2012584
[62] Antitumor effect of novel berberine derivatives in breast cancer cells – https://pubmed.ncbi.nlm.nih.gov/24000115/
[63] Berberine reverses lapatinib resistance of HER2-positive breast cancer cells by increasing the level of ROS – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5036410/
[64] The Anti-Cancer Mechanisms of Berberine: A Review – https://www.dovepress.com/the-anti-cancer-mechanisms-of-berberine-a-review-peer-reviewed-fulltext-article-CMAR
[65] Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states – https://pubmed.ncbi.nlm.nih.gov/16873688/
[66] Berberine is a potential therapeutic agent for metabolic syndrome via brown adipose tissue activation and metabolism regulation – https://pubmed.ncbi.nlm.nih.gov/30662589/
[67] Synergistic chemopreventive effects of curcumin and berberine on human breast cancer cells through induction of apoptosis and autophagic cell death – https://www.nature.com/articles/srep26064
[68] Metformin and berberine, two versatile drugs in treatment of common metabolic diseases – https://www.oncotarget.com/article/20807/text/
[69] Effects of berberine on lipid profile in subjects with low cardiovascular risk – https://www.tandfonline.com/doi/abs/10.1517/14712598.2013.776037
[70] The Effects of Berberine on Blood Lipids: A Systemic Review and Meta-Analysis of
Randomized Controlled Trials – https://bit.ly/3vZOU26
[71] Low-Dose Berberine Attenuates the Anti-Breast Cancer Activity of Chemotherapeutic Agents via Induction of Autophagy and Antioxidation – https://journals.sagepub.com/doi/full/10.1177/1559325820939751
[72] Article: Clinical Applications for Berberine – Potential therapeutic applications in metabolic syndrome, type 2 diabetes, and dyslipidemia
https://www.naturalmedicinejournal.com/journal/2012-12/clinical-applications-berberine