Advances in Natural Compound Based Formulas for Ferroptosis-Induced Cancer Therapy

  • Complementary and Alternative Medicines (CAM)
  • Ferroptosis
  • Integrative Oncology
  • Supplements

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New Paradigm for Ferroptosis-Based Cancer Therapy

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 was granted by the author Dr. Daniel Thomas. See the sharing guidelines for this post above.

Ferroptosis is a form of regulated cell death caused by the accumulation of iron, lipid peroxidation, and rupture of the plasma membrane.
Ferroptosis can be monitored in vitro and in vivo by transplanting human cancer tissue into animals and is now a popular focus of cancer research. There appears to be much interest in developing more powerful ferroptosis-inducing strategies.
Scientists in Shanghai, China have just published research in which they designed and tested a new, very complex biodegradable natural product that releases  Honokiol at the tumour site to induce Ferroptosis while
1) depleting intracellular glutathione (GSH),
2) repressing glutathione peroxidase 4 (GPX4) activity whilst
3) creating the decomposition of intratumoral hydrogen peroxide (H2O2) into Hydroxyl Radicals (OH) 
All this is, and with a bonus of 
4) lactic acid depletion being how they generated the H2O2, which boosts the Fenton reaction.

The Shanghai university's research titled "Lactic acid-responsive sequential production of hydrogen peroxide and consumption of glutathione for enhanced ferroptosis tumour therapy", published in March 2024, describes the in Vitro and In Vivo Observations of the synergistic effects and Ferroptosis efficacy, including cascade reactions, lactic acid-responsive sequential production of H2O2, the successful release of Honkiol to the tumour site. Read the research publisher's intro and snippets for free here

Given that this new, very complex, yet natural product designed for cancer patients is not yet available, I wondered how we could try our best to do what we can with similar mechanisms of action with compounds we can access.

Firstly, many cancer patients today believe that implementing an Artemisinin protocol may help kill cancer cells through the mechanism of ferroptosis. In line with this new complex delivery system research, adding two more supplemental formulas to such a protocol can increase our chances of inducing ferroptosis.
Research into Liposomal Honokiol and Liposomal Piperlongumine for cancer suggests they are potent allies in reducing intracellular glutathione (GSH) and repressing glutathione peroxidase 4 (GPX4). These actions were both critical to the Shanghai team when designing their complex formula.

Honokiol induces ferroptosis in colon cancer cells by regulating GPX4 Activity In Vivo

Ten mice were injected with RKO cells and divided into two groups. One group was injected with GPX4, and the other with a control vector. Both groups received Honokiol for four weeks and tumor volumes were recorded every two days. The tumour volumes were significantly lower in the vector group than in the GPX4 overexpression group (see image). The Ethics Committee of Central South University approved the animal experiments. Read the article here. You can also continue to learn more about Honokiol in cancer research, including dosing and new bio-available Honokiol formulas that are accessible to patients worldwide here.

Piperlongumine (PL) increases the sensitivity of colorectal cancer cells to radiation: Involvement of ROS production via dual inhibition of glutathione and thioredoxin systems

This research demonstrates that PL overcomes both hypoxic and intrinsic radioresistance of colorectal cancer cells, subsequently delaying tumour growth and improving the survival rate of tumour-bearing mice. The mechanisms underlying the radiosensitizing effect are linked to DNA damage, cell cycle arrest, and inhibition of cellular respiration induced by upregulated ROS production due to decreased GSH and inhibition of TrxR. PL induced excessive production of ROS due to depletion of glutathione and inhibition of thioredoxin reductase.

 To get the bigger picture on Lignosomal Honokiol and Lignosomal Piperlongumine research for cancer and considerations on the correct type of supplement and dosing, see my previous healing cancer support blog articles on Piperlongumine here and Honokiol here.

More in the Healing Cancer Study Support Group thread.
Our private Facebook Healing Cancer Study Support Group has threads and external links dedicated to sharing and discussing the research on Ferroptosis and Honokiol. Group members logged into Facebook can learn more and join the discussion via the link in our A-Z directory of threads and files.

Healing Cancer Study Support Group members logged into Facebook can read more, share and join the discussion 

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MCS Formulas Pro Liposomal Honokiol
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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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