Five natural, bioactive compounds - psoralen, curcumin, olive oil, anthocyanins and beta glucans - have been shown to improve HER2 treatments while also being active against HER2 positive breast cancer in their own right.
1. Psoralen has anti-HER2 activity
Psoralen is a natural bioactive compound found in foods such as figs, parsley and celery. Psoralea corylifolia is an important plant in both Ayurvedic and Chinese medicine. Its seeds contain high levels of psoralen.
Now, scientists from Duke Medical Centre in Carolina have found (1) that it can block the signaling pathway of the HER2 receptor, which is overproduced in 15-25 per cent of breast cancers and in other cancers involving tumours such as ovarian and colorectal.
If HER2 is overproduced, the result is an aggressive cancer and uncontrolled cell growth. Human Epidermal Growth factor 2 is a very important oncoprotein.
Herceptin can act against this growth but tends to run out of steam after 2 years. That does not seem to be the case for Psoralen.
Psoralen has long been proven to disrupt DNA replication and cause apoptosis (cancer cell death) when activated by UV light. It is widely used in the treatment of psoriasis, eczema and surface T-Cell lymphoma. This new action was unexpected but confirmed by the scientists led by Dr. Neil L. Spector Associate Professor of Medicine at Duke.
For a longer list of research showing many more ways of tackling HER2 cancer go HERE
Psoralen is also known as psoralene and is a leading compound in the group of natural compounds called furocoumarins. It is related to coumarin.
2. Curcumin inhibits HER2 positive breast cancer
Curcumin has been shown (2, 3, 4) to have two major benefits in Her-2 cancers. Firstly, curcumin enhanced the efficacy of chemotherapy by tailoring p65NF-κB-p300 cross-talk in favor of p53-p300 for breast cancer.
Secondly, it decreases HER2 oncoprotein, and phosphorylation of AKT. It also reduces expression of a number of oncogenes.
In a 2012 study from scientists in Taiwan, there was direct comparison between curcumin and Herceptin and Taxol, both in vitro and in vivo in mice. Curcumin can significantly increase the efficacy of low doses of Herceptin. They actually have a synergistic effect. This was especially marked in ER+, HER2+ breast cancers.
However, where high doses of Herceptin were used, curcumin made little difference.
What was of great significance was where curcumin was used when Herceptin had stopped working or the breast cancer was resistant to Herceptin. Curcumin carried on working.
Finally, in terms of tumour size, Herceptin was shown to reduce tumour size by 86.7% while curcumin alone reduced Her2 positive breast cancer tumours by 76.7%.
Curcumin should be taken with fats and oils (for example, with Extra Virgin Olive oil, or in cooking) and piperine, the active ingredient of black pepper.
3. Polyphenols in Olive Oil inhibit HER-2 Breast cancer
According to a 2009 research report from Dr. Javier A Mendez of the Catalan Institute of Oncology, Girona, Spain, extra virgin olive oil can inhibit the growth of HER-2 Breast cancer. The researchers found that the polyphenols reduced levels of HER-2 protein and induced cell death.
This finding was then backed up by another in 2011. Again it was Dr. Javier A Mendez though by now he was at Northwestern School of Medicine in Chicago. He confirmed that oleic acid in Olive oil, an Omega-9 fatty acid) inhibited HER-2 protein production.
"To our knowledge this is the first report that a dietary monounsaturated fatty acid previously suggested to be protective against breast cancer significantly down-regulates the expression of Her-2/neu, cutting it by up to 46%."
However he went on to say that olive oil made the drug Herceptin work better:
“Moreover, in our tests, oleic acid’s inhibition of HER-2/neu synergistically interacted with Herceptin-based immunotherapy by promoting the death of breast cancer cells exhibiting high levels of the oncogene.”
4. Black rice anthocyanins inhibit HER2 positive breast cancer
In a massive screening exercise in 2013 by Chinese scientists through the New Jersey Medical School studying natural compounds against HER2 positive breast cancer, several emerged with potential. In particular, two from black rice. ‘Peonidin-3-glucoside and cyaniding-3-glucoside inhibit the phospho-HER2 and phospho-AKT and were confirmed to induce HER2-psotive breast cancer cells apoptosis both in vitro and in vivo. Peonidin-3-glucoside and cyaniding-3-glucoside treatments significantly reduced the tumour size and volume in vivo compared to the control group’.
To put this in context, “Just a spoonful of black rice bran contains more health promoting anthocyanin antioxidants than are found in a spoonful of blueberries, but with less sugar and more fiber and vitamin E antioxidants,” said Zhimin Xu, Associate Professor at the Department of Food Science at Louisiana State University Agricultural Center in Baton Rouge, La., who reported on separate research on black rice bran from rice grown in the Southern states of America (5).
5. Beta Glucans inhibit HER-2 protein production and make Herceptin work better
Since 2002 complex polysaccharides known as beta-glucans, which are found in bacterial and microbial cell walls and in mushrooms, have been known to power up various aspects of the immune system.
A 2007 study showed they can prevent cancer formation, inhibit tumour growth and prevent metastases. They can be used with chemo and radiotherapy, and to improve the effectiveness of monoclonal antibodies (6).
By 2014, there was a study from Dr. Zainab Jafaar and his team showing that beta-glucans significantly inhibited oestrogen-negative (ER-) breast cancer growth.
And by 2015, Dr. Z Nasrollahi and his team were using 1.3 beta-glucans to improve HER-2 treatment therapies by carrying Doxorubicin (7)
Go To: Epigenetics and reversing cancer
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References
1. Natural Compound Attacks HER2 Positive Breast Cancer Cells; Feb 17, 2014; - https://corporate.dukehealth.org/news/natural-compound-attacks-her2-positive-breast-cancer-cells
2. Sen GS, Mohanty S, Hossain DM, Bhattacharyya S, Banerjee S, Chakraborty J, et al. Curcumin enhances the efficacy of chemotherapy by tailoring p65NFκB-p300 cross-talk in favor of p53-p300 in breast cancer. J Biol Chem. 2011;286:42232–42247
3. Lai HW, Chien SY, Kuo SJ, Tseng LM, Lin HY, Chi CW, et al. The potential utility of curcumin in the treatment of HER-2-overexpressed breast cancer: an in vitro and in vivo comparison study with herceptin. Evid Based Complement Alternat Med. 2012;2012:486568.
4. The Effect of Curcumin on Breast Cancer cells - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3706856/
5. Selective Anti-Proliferation of HER2-Positive Breast Cancer Cells by Anthocyanins Identified by High-Throughput Screening - http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0081586
6. Effects of beta-glucans on the immune system. Medicina (Kaunas). 2007;43(8):597-606.Akramiene D1, Kondrotas A, Didziapetriene J, Kevelaitis E.
7. Functionalized nanoscale β-1,3-glucan to improve Her2+ breast cancer therapy: In vitro and in vivo study; https://pubmed.ncbi.nlm.nih.gov/25597638/