Honokiol possesses powerful anti-cancer properties

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Honokiol - A Promising Over the Counter Anti-Cancer Compound

Author Credit: The information in this post was originally shared to members of the Healing Cancer Study Support Group in July 2023. Permission to share the information here on MyHealingCommunity.com was granted by the author Dr. Daniel Thomas. See the sharing guidelines for this post above.

Honokiol shows promise in preclinical and early clinical studies for its anti-cancer mechanisms.

The structural diversity and easy binding ability of natural compounds make them unique in participating in the physiological process of life. Nature is an essential resource for discovering anti-cancer drugs or lead compounds, with 80-83% of small-molecule anti-cancer drugs available today being derived from natural products or their modified derivatives.

Research on the mechanisms of the Honokiol the compound extracted from Magnolia bark is still ongoing. Honokiol has been found to work in many powerful ways.

One of the ways Honokiol stands out is that "Honokiol can decrease PI3K/mTOR mediated immunoresistance in glioma, breast and prostate cancer cells through PI3K/mTOR pathway inhibition, without significantly affecting pro-inflammatory T cell function."

The Effects of Honokiol on Cancer Cell Metabolism

Honokiol inhibits cancer cell growth by reducing energy production through glycolysis. These effects are dependent on HIF1α. In HIF1α driven glycolysis, Honokiol can decrease glucose uptake and lactic acid production while increasing oxygen consumption. Radiation therapy and chemotherapeutic agents like doxorubicin and cisplatin can activate HIF1α, which leads to increased HIF1α driven glycolysis in cancer cells and resistance to treatment under hypoxic conditions. Even targeted therapies like TKIs can induce HIF1α driven glycolytic metabolism in tumours.

When viewed through the lens of anti-fungal research, Honokiol triggers signalling pathways that generally respond to oxidative stress, modulated glucose transporters and glycolysis metabolic enzymes, resulting in a decrease in ATP production and activation of cell death pathways.

Honokiol Targets Cancer Angiogenesis

Tumours rely on angiogenesis, as the blood supplies the nutrients and growth the tumour requires. Honokiol has been shown to possess anti-angiogenic properties, which may help to slow down the growth and spread of tumours. The development of blood vessels relies on endothelial cells, which Honokiol has been found to inhibit. Honokiol can suppress pro-angiogenic factors, including vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF). All these factors promote angiogenesis and encourage the growth of blood vessels, but Honokiol can down-regulate their expression. Honokiol also inhibits interleukin-induced angiogenesis in the tumour microenvironment through the NF-κB signalling pathway.

Honokiol disrupts pathways involved in angiogenesis.

Honokiol inhibits MMPs and Increases TIMP-1 and TIMP-2

Honokiol Studies have demonstrated that Honokiol can decrease the levels of MMPs, including MMP-2, MMP-9, and MMP-14. As many know, these MMPs are often linked to cancer progression and metastasis. Honokiol can limit the production of these enzymes, which can reduce their ability to break down the extracellular matrix (ECM) and enable tumour invasion.  TIMP-1 and TIMP-2 are increased, and the activity of the MMPs is significantly reduced, suppressing tumour growth

Not only that but, Honokiol can also directly target the already active sites of MMPs to prevent them from breaking down important ECM components such as collagen and fibronectin. By reducing MMP activity, Honokiol can help preserve the ECM's integrity, which is crucial in preventing tumour invasion and metastasis.

 It is important to note that regulating MMP activity is crucial in the fight against cancer, and using a highly bioavailable, pure, high-strength Honokiol may be highly beneficial in achieving this goal. Honokiol's effects on MMPs vary depending on cancer type, microenvironment, and experimental conditions.

Honokiol induced both autophagy and apoptosis via the PI3K/Akt/mTOR signalling pathway

Unlike other PI3K/mTOR inhibitors, Honokiol can reduce this pathway's activity in tumour cells while leaving critical pro-inflammatory T cell functions unaffected. Specific inhibitors like LY294002, Wortmannin, AKT inhibitor III, and Rapamycin do not have this selective effect.

In cancer, the PI3K/AKT/mTOR pathway can become disrupted, leading to an increase in signals for cell growth and survival. This pathway plays a vital role in regulating cell growth, metabolism, and survival and is crucial for several cellular processes, such as differentiation, proliferation, and survival. The PI3K/AKT/mTOR pathway is of utmost importance in ongoing cancer research, as it is intricately linked to comprehending the mechanisms of treatment resistance in chemotherapies, targeted therapies, and immunotherapies.

Many cancer cell types are responding well to Honokiol

Honokiol has demonstrated good anti-cancer activity against various cancer cells, including breast, lung, bone, colon, bladder, brain, and blood cancer cells. Recent research suggests that Honokiol may effectively overcome immunotherapy resistance in certain types of cancer, such as glioma, breast, and prostate cancer. Dig further here

Research has also shown that Honokiol has an inhibitory effect on NF-κB activity in various types of cancer, including breast cancer, cholangiocarcinoma, colon cancer, liver cancer, lung cancer, myeloma, ovarian cancer, and skin cancer. In an osteosarcoma cell model, Honokiol can both prevent the growth of tumours and increase their rate of apoptosis.

Honokiol caused an increase in the expression of Bcl-2-like protein 4, caspase-3 and p53 protein expression while suppressing the expression of cyclin D1 protein in osteosarcoma cells.

Honokiol and Breast Cancer alone and in combination with oncology drugs. It has been proven to inhibit growth in both estrogen receptor-positive and -negative cell lines, including drug-resistant breast cancer cells. This inhibition is associated with the arrest of cell cycle and the induction of apoptosis. Once again, Honokiol also attenuates the PI3K/Akt/mTOR signalling pathway and shows synergistic effects when combined with the mTOR inhibitor rapamycin.

Honokiol can potentially inhibit the cell cycle of metastatic breast cancer stem cells. This research article on Honokiol in 2022 focused on breast cancer stem cells and their role in chemoresistance, metastasis, and poor prognosis of breast cancer. The authors investigate the potential of Honokiol to target BCSCs and modulate the tumour microenvironment for improved immunotherapy. Using bioinformatics analyses, they predict Honokiol protein targets, and in concert with leading breast cancer projects worldwide pinpoint genes differentially expressed in metastatic breast cancer stem cells. The therapeutic targets of Honokiol include the most common metastatic breast cancer genes CCND1, SIRT2, AURKB, VEGFA, HDAC1, CASP9, HSP90AA1, and HSP90AB1. Honokiol has the potential to inhibit the cell cycle of metastatic breast cancer stem cells. The same paper also highlights Honokiol's impact on various signalling pathways and its potential as an immunotherapeutic agent for mBCSCs.

Overall, Honokiol is a promising treatment for breast cancer.

A study on NSCLC cells discovered that Honokiol will bring about G0/G1 phase cell cycle arrest, apoptosis and autophagy in cancer cells. Cancer can use autophagy to escape cell death, so by simultaneously blocking autophagy with an autophagic inhibitor; they increase the compound’s anti-cancer activity both in vitro and in vivo. This work implies that autophagy was protective in Honokiol-induced cancer cell death. The study suggests that a bioavailable Honokiol combined with an autophagic inhibitor could be a viable option for further investigation into NSCLC treatment. A clinical trial is underway in China.

Healing Cancer Study Support Facebook Group Members:

Click here and login into Facebook to visit the Cancer study support group conversation thread for Autophagy

Where to Buy Bioavailable Pure Honokiol 

It's important to note that there are only three reliable sources for pure Honokiol: Clinical Synergy, Econugenics and MCS Formulas. At MCS Formulas, you can find the exact same compounds as at Clinical Synergy and Econugenics, whereas MCS capsules have no additives and are priced about 30-40% lower. And MCS donates 50% of profits to very worthy cancer research. The purity and identity of the MCS Formulas ingredients are tested with Eurofins in each batch. Additionally, MCS Formulas carry an improved absorption Honokiol called Pro Liposomal.

For anyone who can't take liposomal and has to have the non-liposomal here's the low down on price; Honokiol Pures compared: Eco Nugenics Honopure is nearly twice the price and not pure at all. $112 US dollars for 120 x 250mg capsules that have fillers like tapioca starch too. Where as MCS pure Honokiol (note this is not the Lipo pro simply the pure)
Euro price on the website is equivalent to $65 US dollars for 120 x 250mg capsules with nothing else added  + get 5% off with discount code: abbey5

The MCS Formulas Pro Liposomal Honokiol price is Euro 37.50 for 60 capsules which today is US $41.00 and for a 50kg person taking the lower end of the cancer dose per day 10mg per kilo is 500mg per day being 2 capsules a day making one bottle per month the required amount. Note this is of 'liposomal' as the bioavailability is more aligned with studies. The non-liposomal is not bio-available enough on its own at this dose. 

Healing Cancer Study Support Facebook Group Members:

Click here and Login to Facebook to share photos or links to products and discuss the content per capsule further in the group’s thread dedicated to Honokiol

Honokiol Safety and Dosing for Humans - combating drug-resistant and hormone-resistant cancer tumours

I'm not suggesting high dosing, but it's worth taking a look at a micro size human case study on Honokiol-IV as an adjunct treatment for solid tumours. The study demonstrates that Honokiol can be safe and effective in combating drug-resistant and hormone-resistant tumours.

After a 24-hour observation period following the successful administration of an oral test dose of Honokiol (250 mg capsule; 98% Honokiol), the patients received an initial dose of 500 to 750 mg Honokiol equaling 10 mg/kg body weight, administered intravenously over 45 to 60 minutes with close monitoring. Following successful administration, the dose was escalated on an individual basis over a 1- to 2-week period, to a maximal dose of 50 mg/kg. The side effect that was most commonly reported was temporary sedation, but it went away after the treatment. Haematological values remained stable, with no treatment-related adverse events. Other side effects are reported see the article.

A world-first high-strength bioavailable pro-liposomal over-the-counter Honokiol by MCS Formulas B.V. (2023, July 19) is now available from MCS Formulas.

References

Borgonetti, V., Governa, P., Manetti, F., Miraldi, E., Biagi, M., & Galeotti, N. (2021). A honokiol-enriched Magnolia officinalis Rehder & E.H. Wilson. bark extract possesses anxiolytic-like activity with neuroprotective effect through the modulation of CB1 receptor. The Journal of pharmacy and pharmacology, 73(9), 1161–1168. https://doi.org/10.1093/jpp/rgab067

Bai, X., Cerimele, F., Ushio-Fukai, M., Waqas, M., Campbell, P., Govindarajan, B., Der, C. J., Battle, T. E., Frank, D. A., Ye, K., Murad, E., Dubiel, W., Soff, G. A., & Arbiser, J. L. (2003). Honokiol, a Small Molecular Weight Natural Product, Inhibits Angiogenesis in Vitro and Tumor Growth in Vivo. Journal of Biological Chemistry, 278(37), 35501–35507. https://doi.org/10.1074/jbc.m302967200

Banik, K., Ranaware, A. M., Deshpande, V. S., Nalawade, S. P., Padmavathi, G., Bordoloi, D., Sailo, B. L., Shanmugam, M. K., Fan, L., Newsholme, P., Sethi, G., & Kunnumakkara, A. B. (2019). Honokiol for cancer therapeutics: A traditional medicine that can modulate multiple oncogenic targets. Pharmacological Research, 144, 192–209. https://doi.org/10.1016/j.phrs.2019.04.004

Cheng, X., Wang, F., Qiao, Y., Chen, T., Fan, L., Shen, X., Yu, D., Huang, Y., & Wei, M. (2023). Honokiol inhibits interleukin-induced angiogenesis in the NSCLC microenvironment through the NF-κB signaling pathway. Chemico-Biological Interactions, 370, 110295. https://doi.org/10.1016/j.cbi.2022.110295

Crane, C. A., Panner, A., Pieper, R. O., Arbiser, J. L., & Parsa, A. T. (2009). Honokiol-mediated Inhibition of PI3K/mTOR Pathway. Journal of Immunotherapy, 32(6), 585–592. https://doi.org/10.1097/cji.0b013e3181a8efe6

Eliaz, I., & Weil, E. (2020). Intravenous Honokiol in Drug-Resistant Cancer: Two Case Reports. Integrative cancer therapies, 19, 1534735420922615. https://doi.org/10.1177/1534735420922615

Khan, M. I., Khan, A., Zafar, S., Aslam, S., Khan, A., Shal, B., Haider, R., Din, F. U., & Khan, S. (2023). Anti-nociceptive effects of magnolol via inhibition of TRPV1/P2Y and TLR4/NF-κB signaling in a postoperative pain model. Life Sciences, 312, 121202. https://doi.org/10.1016/j.lfs.2022.121202

Li, Q., Ma, Y., Liu, X., Mu, L., He, B., Wu, K., & Sun, W. (2020). Anti‑proliferative effect of Honokiol on SW620'cells through up-regulating BMP7 expression via the TGF‑β1/p53 signaling pathway. Oncology Reports. https://doi.org/10.3892/or.2020.7745

Li, Z., Dong, H., Li, M., Wu, Y., Liu, Y., Zhao, Y., Chen, X., & Ma, M. (2017). Honokiol induces autophagy and apoptosis of osteosarcoma through PI3K/Akt/mTOR signaling pathway. Molecular Medicine Reports. https://doi.org/10.3892/mmr.2017.8123

Lin, S. Y., Liu, J. D., Chang, H. C., Yeh, S. D., Lin, C. H., & Lee, W. S. (2002). Magnolol suppresses proliferation of cultured human colon and liver cancer cells by inhibiting DNA synthesis and activating apoptosis. Journal of cellular biochemistry, 84(3), 532–544. https://pubmed.ncbi.nlm.nih.gov/24147344/

Liu, A., Xun, S., Zhou, G., Zhang, Y., & Lin, L. (2023). Honokiol alleviates sepsis-associated cardiac dysfunction via attenuating inflammation, apoptosis and oxidative stress. Journal of Pharmacy and Pharmacology, 75(3), 397–406. https://doi.org/10.1093/jpp/rgac102

Liu, H., Zang, C., Emde, A., Planas-Silva, M. D., Rosche, M., Kühnl, A., Schulz, C., Elstner, E., Possinger, K., & Eucker, J. (2008). Anti-tumour effect of Honokiol alone and in combination with other anti-cancer agents in breast cancer. European Journal of Pharmacology, 591(1–3), 43–51. https://doi.org/10.1016/j.ejphar.2008.06.026

Ong, C. P., Lee, W. L., Tang, Y., & Yap, W. H. (2019). Honokiol: A Review of Its Anti-cancer Potential and Mechanisms. Cancers, 12(1), 48. https://doi.org/10.3390/cancers12010048

Ponnurangam, S., Mammen, J. M., Ramalingam, S., He, Z., Zhang, Y., Umar, S., Subramaniam, D., & Anant, S. (2012). Honokiol in Combination with Radiation Targets Notch Signaling to Inhibit Colon Cancer Stem Cells. Molecular Cancer Therapeutics, 11(4), 963–972. https://doi.org/10.1158/1535-7163.mct-11-0999

Schang, L. M. (n.d.). Honokiol Inhibits SARS-CoV-2 Replication in Cell Culture at a Post-Entry Step | Microbiology Spectrum. Microbiology Spectrum. https://journals.asm.org/doi/full/10.1128/spectrum.03273-22

Wang, X., Liu, Q., Fu, Y., Ding, R., Qi, X., Zhou, X., Sun, Z., & Bao, J. (2022). Magnolol as a Potential Anti-cancer Agent: A Proposed Mechanistic Insight. Molecules, 27(19), 6441. https://doi.org/10.3390/molecules27196441

Xu, T., Wenyue, T., Zhang, Q., J, L., Liu, Z., Jin, J., Guo, Y., & Bai, L. (2021). Novel 1,3,4-thiadiazole/oxadiazole-linked honokiol derivatives suppress cancer via inducing PI3K/Akt/mTOR-dependent autophagy. Bioorganic Chemistry, 115, 105257. https://doi.org/10.1016/j.bioorg.2021.105257

Yi, X., Qi, M., Huang, M., Zhou, S., & Xiong, J. (2022). Honokiol Inhibits HIF-1α-Mediated Glycolysis to Halt Breast Cancer Growth. Frontiers in pharmacology, 13, 796763. https://doi.org/10.3389/fphar.2022.796763

Zhou, Y., Bi, Y., Yang, C., Yang, J., Jiang, Y., Meng, F., Yu, B., Khan, M., Ma, T., & Yang, H. (2013). Magnolol induces apoptosis in MCF-7 human breast cancer cells through G2/M phase arrest and caspase-independent pathway. Die Pharmazie, 68(9), 755–762. https://pubmed.ncbi.nlm.nih.gov/24147344/

Zhang, F., Ren, H., Shen, J., Zhang, X., Ye, H., & Shen, D. (2017). Magnolol suppresses the proliferation and invasion of cholangiocarcinoma cells by inhibiting the NF-κB signalling pathway. Biomedicine & Pharmacotherapy, 94, 474–480. https://doi.org/10.1016/j.biopha.2017.07.085

Zhao, M., Zheng, Y. H., Zhao, Q. Y., Zheng, W., Yang, J. H., Pei, H. Y., Liu, L., Liu, K. J., Xue, L. L., Deng, D. X., Wang, L., Ma, X., Fu, S. H., Peng, A. H., Tang, M. H., Luo, Y. Z., Ye, H. Y., & Chen, L. J. (2021). Synthesis and evaluation of new compounds bearing 3-(4-aminopiperidin-1-yl)methyl magnolol scaffold as anti-cancer agents for the treatment of non-small cell lung cancer via targeting autophagy. European journal of medicinal chemistry, 209, 112922. https://doi.org/10.1016/j.ejmech.2020.112922

DISCLAIMER: Any and all information in this post was gathered from published research in cell lines or animals, or from typical clinical use. It may not be complete, may not have not been verified in humans, and is NOT meant or given as medical advice, but only as a guide to further exploration.

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