Natural Compounds can fight HER2 positive breast cancer: Review

Natural Compounds can fight HER2 positive breast cancer: Review

Research advances have shown a great many natural compounds such as berberine, melatonin, turkey tail mushrooms, honokiol, vitamin D, melatonin and apigenin-containing compounds, to be capable of helping fight HER2 breast cancer; here we present a Review of the research.

In a separate article from 2017, we originally covered 5 natural compounds - psoralen (figs), curcumin, olive oil, beta glucans and anthocyanins, which each in early research, seem to have strong actions against HER2 positive breast cancer. Here is an important update.

Her-2/neu (ErbB2) is a transmembrane tyrosine kinase and acts as a co-receptor for the other EGFR family members. It is well known that high expression of Her-2/neu is associated with a poor prognosis in breast cancer. It is also present in other cancer.

1. Apigenin causes a decrease in HER2 expression

While high doses of natural apigenin did not display estrogen-like activity and even suppressed  ER receptors, cultivation of HER2-positive breast cancer cells in the presence of apigenin resulted in a decrease in HER2/neu expression, accompanied by significant PARP activity (1). Apigenin seems a powerful breast cancer natural compound. It is found in cleavage of an apoptosis substrate PARP.  Apigenin-rich foods include spinach, oregano, parsley, onions, coriander, basil, and ... red wine.

2. Vitamin D suppresses HER2 expression

We know that vitamin D 'arms' the immune system. It is not a vitamin, it's a hormone and T-cells, B-cells, antibodies and other members of the immune system exhibit receptor sites for the vitamin. It also corrects cancer cells and has epigenetic activity. In 2017 research (2) it was shown to influence Er+ve activity and sprress HER2 expression. Vitamin D is essential in the fight against cancer. Levels should be above 80 nmol/L to avoid deficiency.

3. Honokiol suppresses HER2

HER2 expression is not only found in certain breast cancers but also in colorectal cancer and gastric cancer; to give HER2 its full name, it is Human Epidermal Growth Factor Receptor 2.  A 2020 study (3) showed that the Traditional Chines Medicine Honokiol, from the Magnolia bush, could suppress HER2 expression in gastric cancer. Honokiol has many actions against many cancers.

4. Berberine suppresses overexpression of HER2 in breast cancer

The herb Berberine is a natural alkaloid with significant antitumor activities against many types of cancer cells, At CANCERactive we strongly support its use over Metformin in almost all types of cancer. It has so many more benefits. Here the research (4) showed that, not only did berberine  suppress HER2 expression, it nduced G1-phase cell cycle arrest by interfering with the expression of cyclins D1 and E and induced cellular apoptosis. The research showed Berberine was particularly enhancing of Paclitaxel against HER2 expression. Berberine was particularly impressive in the modification of the HER2/PI3K/Akt signaling pathway.

5. Melatonin represses HER2 expression

Melatonin, often called the sleeping hormone when 60-100 times more is produced by your body during the day by the action of infra-red sunlight on your mitochondria, is the biggest antioxidant we make and a huge antiinflammatory. It has a number of significant actions against cancer cells. Melatonin, in fact, also represses metastasis in HER2-Postive human breast cancer cells by suppressing RSK2 Expression (5).

6. Medicinal Mushrooms reduce HER2 expression

Medicinal Mushrooms contain high levels of polysaccharides and glycoproteins with beta glucan polysaccharides having significant health benefits. We talked about the research on the benefits od beta glucans with HER2 cancer in out 2017 article.

Research, including four Nobel Prizes, shows that glycoproteins can improve cellular communications. They also help hormones do their job better, they help receptor sites receive the messages that they are supposed to receive, and they help your immune system see the rogue cells and differentiate them from the healthy cells. 

PSK in particular from Turkey Tail mushrooms, activates human NK cells and enhances the anti-tumor effect of HER2-targeted monoclonal antibody treatment Herceptin (6). "Oral administration of PSK significantly potentiated the effect of anti-HER2/neu therapy." Turkey tail is available as an organic powder and the usual dose is 2 gm. 

7. Quercetin reduces HER2 expression 

Quercetin is a flavonoid present in many vegetables and fruits. It has many studies showing effects against cancer. One of those  showed that quercetin decreased the level of Her-2/neu protein in a time- and dose-dependent manner and also inhibited the downstream PI3K-Akt signaling pathway that promotes the cancer cell survival in Her-2/neu overexpressing breast cancer cells (7).

 8. Quercetin and Turmeric jointly suppress HER2 protein levels 

In our 2017 article on 5 natural compounds effective against HER2 positive cancer, we presented at least three studies on the benefits of turmeric (or curcumin). In a 2020 study, researchers showed that low concentrations of curcumin ican nhibit Her2-Akt pathway components  and that other dietary botanicals such as Quercetin could potentiate this. They also found this synergy between Quervetin and Curcumin blocked the cancer cells ability to block Lapatinib, an anti-HER2 breast cancer drug (8).

Don't forget the anti-HER2 benefits of Olive Oil, Psoralen (figs), anthocyanins (aubergine, dark cherries, dark plums, black rice, dark chocolate) and beta glucan (medicinal mushrooms, mother's milk).

Go to: Five Natural Compounds attack HER2 expression in cancer



1. Apigenin Inhibits Growth of Breast Cancer Cells: The Role of ER and HER2/neu; A M Scherbakov; Acta Naturae. 2015 Jul-Sep;7(3):133-9

2. Influence of vitamin D signaling on hormone receptor status and HER2 expression in breast cancer; Xi Zhang et al; ncer Res Clin Oncol

3. Honokiol Suppression of Human Epidermal Growth Factor Receptor 2 (HER2); Yidan Yan et al; Med Sci Monit. 2020 Aug 30:26:e923962.

4. Growth Suppression of HER2-Overexpressing Breast Cancer Cells by Berberine via Modulation of the HER2/PI3K/Akt Signaling Pathway;  Han-Pen Kuo et al; Agriculture and Food chemistry

5. Melatonin Represses Metastasis in Her2-Postive Human Breast Cancer Cells by Suppressing RSK2 Expression; Lulu Mao et al; Mol Cancer Res; 2016 Nov;14(11):1159-1169.

6. TLR2 agonist PSK activates human NK cells and enhances the anti-tumor effect of HER2-targeted monoclonal antibody therapy;   Hailing Lu et al;  Clin Cancer Res. 2011 Nov 1; 17(21): 6742–6753.

7. Quercetin-induced ubiquitination and down-regulation of Her-2/neu; Jae-Hoon Jeong et al; J Cell Biochem; 2008 Oct 1;105(2):585-95

8. Lower concentrations of curcumin inhibit Her2-Akt pathway components in human breast cancer cells, and other dietary botanicals potentiate this



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