Honokiol helps restrict tumour growth and metastases; helps chemo and radiotherapy

Honokiol helps restrict tumour growth and metastases; helps chemo and radiotherapy
Traditional Chinese Medicine Honokiol has many effects against cancer

Honokiol is an important bioactive compound derived from several species of Magnolia and from the bark, cones and leaves. It has long been popular in Chinese Medicine. Most usually the bark is the source and there are, in fact two active ingredients - Honokiol and Magnolol.  It is known to have anti-inflammatory, anti angiogenic, antioxidant and anti-cancer properties. Honokiol acts synergistically with bioactive ingredients in ginger.

Honokiol works in many ways against cancer

A 2012 review confirmed that Honokiol (HNK) had worked against multiple cancer signalling pathways, both in vitro and in animal models. The pathways targeted include: 
  • Nuclear Factor Kappa B (NFKB),
  • Signal Transducers and Activator of Transcription 3 (STAT3),
  • Mammalian Target of Rapamycin (m-TOR),
  • Mitogen-Activated Protein Kinases (MAPK), and,
  • Epidermal Growth Factor Receptor (EGFR).

These are strongly featured in cancer initiation, cancer progression and metastases controlling cytokines, adhesion molecules, cell cycle molecules and cell death systems. Honokiol has shown positive effects in glioma, Chronic Lymphocytic Leukaemia (CLL), NSCLC, pancreatic, colorectal, prostate and breast cancer cell lines and/or those cancers in animal models. It also appears to increase the effectiveness of chemotherapy and radiotherapy.
Back in 2012, researchers were then stressing that the particular success of Intravenous use of Honokiol in animals should prompt urgent human clinical trials.
Honokiol limits metastases in many cancers
Also in 2012, a study using mice with osteosarcoma showed that Honokiol, while it did not reduce the primary tumour, stopped spread of the cancer to lungs and liver by a huge 60% and 80% respectively. In 2013, researchers Singh and Katiyar found that honokiol could inhibit metastases and cell migration in vitro. In particular, honokiol restricted the Cox-2 and prostaglandin E2 (PEG2) inflammatory process that aids metastases(1).
They had shown previously much the same benefits in stopping breast cancer metastases(2). 
In a separate study in 2013, Singh, Prasad and Katiyar showed that honokiol could kill NSCLC both in vitro and in animals(3). 
In 2014, researchers from Johns Hopkins, Emory School of Medicine and Maryland Medical School combined to show that Honokiol could block breast cancer cell growth and metastases via STAT3 and cadhedrin.
In 2016, a team from Mitchell Cancer Institute in South Alabama showed that Honokiol could suppress pancreatic tumour growth, invasiveness and metastases by stopping the molecular cross-talk between various cancer signalling pathways. A ’significant inhibition of mouse tumour growth occurred along with a complete restriction of distant metastases’.

In 2017 it was shown to inhibit NSCLC Lung cancer metastases through the STAT3 pathway and be capable of stopping Lung cancer development particularly to the lymph nodes and to the brain. In fact, Honokiol stopped progression and metastases to the brain in one third of the mice.

Honokiol increases cancer cell sensitivity to chemo and radiotherapy

In 2016, researchers from the Wisconsin Cancer Center (Pan, Lee, Wang and You) confirmed that Honokiol targeted the cancer cell mitochondria to halt progression and metastases in vitro and in animal models.

They also confirmed that Honokiol could sensitise cancer cells making chemotherapy and radiotherapy more effective and stated that its use should mean that less chemotherapy drug levels needed to be used when Honokiol was present. They also talked of how Honokiol could prevent chemo resistance and increase the life span of drugs.

Several studies have shown that Honokiol radio sensitises colorectal cancer cells in vitro and in vivo. Honokiol had previously been shown to be a ’potent chemotherapy agent against human colorectal cancer’.

In a 2017 study honokiol significantly improved the effects of doxorubicin in glioma treatment. This was shown in vitro and in vivo. It has been known to cross the Blood Brain Barrier in both mice and rats since 2011. Honokiol has been shown to repress human glioma growth by inducing apoptosis and cell cycle arrest. The 2016 study concluded that there was potential for the use of Honokiol in GBM. In 2018, Honokiol has been shown to improve the effectiveness of Temozolomide on glioma cells with increased autophagy and apoptosis.

Honokiol inhibits androgen receptor activity in prostate cancer

A 2014 study from researchers at the University of Pittsburg, showed that Honokiol inhibited the growth of prostate cancer cells in vitro and in animals. HNK also induced apoptosis (cancer cell death). A 2009 study using magnolol from the Magnolia tree bark showed that it caused apoptosis in prostate cancer cells by inhibiting EGFR. A 2015 report in Food Science and Biotechnology magazine noted that magnolia had anti-inflammatory and anti-cancer properties with prostate cancer. It also changed IGF-1 and other proteins in treated cells. Magnolol has also been shown to limit metastases in prostate cancer, and has no effects on healthy cells.

Chris Woollams, former Oxford University Biochemist and a founder of CANCERactive said, "It really is time for human clinical trials. There have been many university teams working on Honokiol showing that it affects multiple cancer pathways, and limits tumour growth, invasiveness and metastases. And it makes chemo and radiotherapy work better. But now we need to know, for example, if it has to be administered intravenously, or will oral use suffice? And we need clearer views on the dosage. It would seem that the standard dose is 200 mg.

We also need to understand the potential side-effects as we know it also has neurological effects - Honokiol raises acetylcholine levels in the brain and can calm stress; and is a sedative according to research from South Carolina Medical School. Is that good, or could that be a problem if you take too much?

It does seem that Honokiol can form a potent double act with PectaSol (Modified Citrus Pectin) in restricting metastases, after trawling various sites on the Internet."
  1. PLoS One 2013 April https://www.ncbi.nlm.nih.gov/pubmed/23580348
2017 Research
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