M0027 Dandelions Just Pretty Flowers or Anti Cancer Powerhouses

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Dandelions are quite the inconspicuous flowers, beloved primarily for the puffy way, in which they spread their seeds. It may seem a little bit of a silly question to ask whether this flower has anti-cancer activity, but one would never know the answer without asking.

During one of our coaching calls, one of our clients mentioned in passing, that an acquaintance had told him about dandelions and asked whether he was using it for its anti-cancer effect. The client replied with no, but the question piqued both his and my interest.

Our three aims at Marchward are as always:

1. Improve patient quality of life.
2. Extend patient duration of life.
3. Increase patient chance of cure.

Thus, we'll take a look at how exactly dandelion seems to support all three items on the above list. I'll reference this list throughout this article, and bring back our journey of discovery to these three foundational aims. It may seem unlikely, that such an inconspicuous yellow flower harbours any anti-cancer potency, but looks can be deceiving.

And as you'll find, dandelion is in this regard more than a little deceiving in its inconspicuousness.

Dandelion as a Modulator of Multiple Signalling Pathways

To give you an overview, I want to briefly talk synoptically about the plethora of signalling pathways dandelion extracts or their constituent compounds have been found to impact, and what this means for cancer. After having gained such an overview, I want to move on to each of the signalling pathways dandelion, its extracts, and their compounds modulate and explore how such modulation affects various cancer subtypes and how it interacts with other interventions.

Extracts or compounds from dandelion have been found to aid in cell cycle arrest and limit proliferation of gastric and breast cancer cells, as well as hepatocellular carcinoma cells through various pathways.¹ If cells want to grow and divide, they need to move through a full cell cycle. Cell cycle arrest simply describes a cell halting in one of the stages of cell cycle.² This mostly happens in the specialised non-proliferative G0 stage.

This would already aid us in Aim 2 – extending patient duration of life by simply slowing down cancer growth – and Aim 3 – increasing chance of cure by giving the treatment regimen more time to unfold its effect.

Dandelion does more than that, though. It also induces apoptosis in breast, cervical, tongue, and gastric cancer cells by various mechanisms.¹ Apoptosis is a tightly regulated sacrificial suicide, which cells can call upon, when they're dysfunctional or when their apoptosis serves their host organism, which in this case is you.³ Cancer cells are almost always found to be incapable or 'unwilling' to induce their own apoptosis.^4–6 Thus, the promotion of apoptosis, especially when selective to cancer cells, is a powerful tool to either help cancer cells with initiating apoptosis or force them to do it.

Again, this helps us in Aims 2 and 3 – extending patient duration of life by killing off cancer cells and increasing chance of cure by virtue of the same.

On top of this, dandelion, its extracts, and their compounds can also inhibit invasion and metastasis.¹ Invasion is necessary for a simply abnormally growing cell mass to dissolve the extracellular matrix usually keeping it somewhat caged and to thus extend into surrounding tissues, threatening tissue and organ function.⁷ Metastasis is a similar process, where cells invade the bloodstream, travel to distal tissues, and then invade those distal tissues.

The inhibition of both simply gives cancer patients longer to live, thus helping us with Aim 2. Furthermore, the inhibition of metastasis and invasion would be expected to help us with Aim 1 – improving cancer patient quality of life by lowering the number and severity of painful metastases.

Dandelion has been found to stimulate autophagy in breast and colon cancer cells via multiple pathways. Autophagy is a process of recycling of cell-internal material and can lead to autophagic cell death.⁸ Escape from autophagic cell death is one of the two foundational prerequisites for cancer malignancy, the other being escape from senescence (or indefinite cell cycle arrest), which makes stimulation of autophagy both highly desirable and synergistic with cell cycle arrest in its anti-cancer action.

And once more, this would aid us in Aims 2 and 3 – extending patient duration of life and increasing chance of cure.

But we're not done just yet. Dandelion and its extracts and compounds have also been found to modulate metabolism in lung and gastric cancer cells.¹ Specifically, they inhibit key enzymes in sugar metabolism and phospholipid synthesis, both of which are required for rapid cancer cell growth. Their inhibition thus is another highly desirable effect. On top of this, dandelion has been found to suppress tumour angiogenesis in hepatocellular carcinoma. Angiogenesis is the process of generating new blood vessels. Inhibition of this process would thus leave a growing tumour deficient in nutrient supply, thus slowing growth, and would make metastasis more difficult due to poorer access to the blood stream.

This last point would aid us in all three Aims – improving patient quality of life by lowering number and severity of painful metastases, extending patient duration of life by slowing down cancer growth, and improving chance of cure by virtue of the same.

Dandelion Promotes Cell Cycle Arrest, Autophagic Cell Death, and Apoptosis

As mentioned above, the properties of dandelion, its extracts, and their compounds to promote cell cycle arrest and induce autophagy are highly synergistic, as they attack the two primary escapes a maturing cancer needs to perform to attain malignancy: escape from senescence and escape from crisis.^1,8 If we reversed these two escapes fully, we could indeed defang cancer, though we wouldn't necessarily be able to cure it just by these two acts alone.

I think it doubtful, that dandelion and its extracts alone are potent enough to fully enforce cell cycle arrest and autophagic cell death in all cancer types, and I think, that precisely our focus on such silver-bullet monotherapies has put us at the current significant disadvantage in our war on cancer. For whilst a maturing cancer needs to escape senescence and crisis, cancer is not just a loss of these controls. It's also an evolutionary process (with caveats),⁹ a process of morphostatic control loss,^10–11 a process of chronic inflammation,¹² a process of metabolic aberration,^13–14 a process of cytoskeletal abnormality,¹⁵ a process of endocrine aberration,^16–17 and a process of acidic damage and transformation.^18–20

This makes it a silly idea to me to attempt the curation of cancer by one single drug, for though such a single-drug approach would certainly be profitable, it's also almost certainly doomed to fail.

So, how can we embolden the anti-cancer effects of dandelion, its extracts, and their compounds? Primarily, we'd want to intensify cell cycle arrest and autophagic induction, especially via different signalling pathways than dandelion itself, for this would allow for efficacy in various cell types, even should they lack some of the signalling pathways or be otherwise aberrant.

Compounds $\psi$-taraxasterol and taraxasterol and polysaccharides from dandelion inhibit expression of cyclin D1 and proliferating cell nuclear antigen – both of which are used in the progression of cells through the cell cycle and DNA replication, respectively, and are thus promotive of cell proliferation – and stimulate expression of p21 and p53 – both of which are tumour suppressor genes, which inhibit the proliferation and promote the death of aberrant cells.^1,21–24 $\phi$-Taraxasterol and taraxasterol also promote cancer cell apoptosis via p53 and mTOR.

Other compounds and extracts have been found to inhibit cell cycle and promote apoptosis through the same and other pathways, like cordycepin from fungi of the Cordyceps genus, EGCG from green tea, resveratrol from grape seeds, and curcumin from curcuma.^25–30

Furthermore, both a ketogenic diet and fasting have been shown to be inducers of autophagy.^31–32 Fasting seems to be a stronger inducer of autophagy than ketogenic diet, simply because fasting provides additional autophagic stimulation via growth factor and amino acid deprivation, which ketogenic diet alone does not.^33–36 Furthermore, extracts from Cordyceps sinensis and Ganoderma lucidum have been shown to modulate autophagy in a way supportive of health,^37–38 as have the compounds Astaxanthin, Curcumin, EGCG, and Resveratrol.^39–42

Now, I think it's wisest here to use multiple strategies to effectuate stable autophagic induction and modulation in order to most robustly achieve our Aims 1 through 3 of improving patient quality of life, extending their duration of life, and improving their chance of cure. Every drop in the bucket could be the one to give us overflow and fully terminate disease progression or perhaps even cure it. Multiplexing mutually supportive interventions is paramount to this effort.

Beyond all of this, dandelion extracts, dandelion root extracts, and taraxasterol have been shown to induce apoptosis in various cancer cell lines.¹ Interestingly, one of the mechanisms, by which dandelion effectuates this is through modulation of mitochondrial membrane potential. This is highly reminiscent to the way, in which dichloroacetate (DCA) induces apoptosis in cancer cells.⁴³ Even more interestingly, DCA achieves this effect by changing fuel partitioning inside cancer cells, inhibiting lactic acid fermentation and boosting mitochondrial oxidative phosphorylation of glycolytic products. Dandelion itself – as mentioned above and discussed in depth below – disrupts cytosolic glycolysis, perhaps thus also necessitating mitochondrial metabolism, which then would normalise mitochondrial membrane potential and lead to apoptosis much as it does with DCA. This is, however, speculative, as the precise mechanism isn't known.

Furthermore, dandelion also directly modulates the activity of Bcl-2 group proteins, which regulate apoptosis, and caspases, which actually execute the biochemical process of apoptosis. This again aids us in Aim 1 of improving patient quality of life, simply by slowing growth of cancer tumour through cell attrition of the growing tumour, thus depriving the tumour of proliferating cells. If this process can be intensified, then we may even be able to achieve Aim 3 by increasing cancer cell death rate beyond their proliferation rate. Again, a combinatorial approach becomes recommendable.

Dandelion Inhibits Cancer Cell Invasion and Metastasis

There are two prevailing hypotheses as to the process underlying the acquisition of migratory competence by cancer cells originating from epithelial cells, which ordinarily are highly immobile.⁴³ To acquire migratory competence cancer cells need to be able to do two things:

1. They need to survive without the contact signalling ordinarily required for epithelial cells not to die.
2. They need to be able to remodel the extracellular matrix, to and by which epithelial cells are bound and restricted.

The two competing – or as I view them: complementing – hypotheses of how this process happens hold either a transition into a mesenchymal or into a myeloid cell state responsible for this acquisition of migratory competence.⁴⁴ Hereby, mesenchymal cells are cells, which ordinarily maintain connective tissue – amongst other things –, and myeloid cells are those cells, which give rise to our blood cells. Understanding of the processes of invasion and metastases are further complicated by recent findings, that cancer cells can also migrate as cell clumps, in which case, they don't need to fully acquire mesenchymal or myeloid features.⁴⁵

In any event, whether one views the maturation of epithelium-derived cancer cells into fully mobile and migration-competent cancer cells as a transition into a blood cell–like state or a connective tissue cell–like state, invasion requires a dissolution of the extracellular matrix around the tumour, so that cells may infiltrate into adjacent tissues, and metastasis requires some survival without contact to the extracellular matrix as the cells – either as singles or clumps – travel through the blood.

Flavonoids (a compound class) from the ethanol extract of dandelion have been shown to reduce migration rates of two human cancer cell lines by 18.32% to 19.33% and reducing their invasion rate by 14.54% to 31.12%.¹ This action is linked amongst other things to its promotion of E-cadherin expression and the inhibition of N-cadherin expression. Interestingly, the above alluded-to epithelial–mesenchymal transition (EMesT) is precisely characterised by a loss or reduction in E-cadherin and a commensurate increase in N-cadherin.⁴⁶ Dandelion inhibits this process on the basic level of gene expression, making it exceedingly valuable.

Furthermore, in another cancer cell line, dandelion extract has been shown to decrease cell migration rate by 35.36% and to decrease invasion rate by 31.20%.¹ Commensurate with this decrease in cell migration and invasion rate was a reduction in expression levels of matrix metalloprotease 2 (MMP-2). MMPs are used in the remodelling of the extracellular matrix, so the curtailing of their expression aids in keeping the extracellular matrix intact and thus restricting cancer cell migration, invasion, and metastasis.⁴⁶ $\phi$-Taraxasterol from dandelion more broadly inhibited the expression of proteins associated with EMesT and commensurately lowered their rates of cell migration and invasion by 68.23% and 51.05%, respectively.

Dandelion also modulates certain inflammatory signallers, increasing expression of tumour necrosis factor $\alpha$ (TNF-$\alpha$), decreasing expression of transforming growth factor $\beta$ (TGF-$\beta$) and interleukin 10 (IL-10), and inhibiting PD-L1.¹ I've discussed the relevance of PD-L1, TGF-$\beta$, and TNF-$\alpha$ in prior articles.^47–49 Nonetheless, I'll reiterate it here and expand it to include IL-10.

To understand this, we must first understand, that macrophages – a kind of immune cell, that eats pathogens and cellular debris amongst many other things – can be polarised in two primary ways. During activation, depending on the co-stimulatory signalling environment, macrophages can polarise into M1 or M2 macrophages.⁵⁰ M1 are hereby pro-inflammatory and improve the killing of defective and infected cells, whereas M2 are immunosuppressive and protect cells from destruction in various ways. That and the fact, that an increase in the number of tumour-associated M2 macrophages is indicative of poor prognosis in cancer patients makes it obvious, that in cancer care, we decidedly want to foster an M1 polarisation.

Now, back to our yellow flower. As stated, dandelion suppresses expression of TGF-$\beta$ and IL-10. Both of these signallers are produced by M2a and M2b macrophages (subtypes of M2) and support the differentiation of M2c macrophages, who aid in tissue remodelling – a process cancer cells can use to improve efficiency of invasion and metastasis by extracellular matrix dissolution, as discussed above.⁵¹ M2d macrophages are largely only found in tumour lesions, but also produce IL-10.

What does this all mean for us? The fact that dandelion reduces both TGF-$\beta$ and IL-10 expression means that it either lowers polarisation of macrophages into the M2 type, lowers the activity of M2 macrophages, or does both. It gets better still. I've mentioned above the other and pro-inflammatory type of macrophage: M1.

M1 macrophages, amongst other factors are stimulated by TNFs – like TNF-$\alpha$ –, the expression of which dandelion promotes.¹ This means, that dandelion seems to change polarisation away from M2 and toward M1 macrophages, which would be helpful in destroying cancer cells. And what's more, dandelion also just so happens to inhibit PD-L1, which is a surface signalling molecule over-expressed by various cancers to suppress tumour-invasive immune cells.⁵² The suppression of its signalling would thus allow for more efficient dispatching of cancer cells.

Again, I think multiplexing dandelion with approaches discussed in my articles on Cordyceps sinsensis, Ganoderma lucidum, and persistent spike protein pathology to improve immune modulation and increase the likelihood of robustly achieving our Aims is wise.^47–49

That being said, dandelion again seems to give us precisely what we'd want. Improving patient quality of life (Aim 1) – by slowing down extracellular matrix remodelling and thus the number and severity of painful metastases –, extending their duration of life (Aim 2) – by virtue of the same and my improving immunological killing of cancer cells –, and improving chance of cure (Aim 3) – by virtue of the two prior points.

Dandelion Modulates Aberrant Sugar and Lipid Metabolism

Cancer cells are often seen to prefer the use of sugar fermentation even under conditions, where the more efficient burning of sugar is available.¹³ This seems to stem from an underlying metabolic incompetence in cancer cells and a demand to provide energy for their rapid growth.

Dandelion here modulates sugar metabolism by inhibiting activities of hexokinase and glyceraldehyde-3-phosphate dehydrogenase, which catalyse the first and sixth steps of glycolysis (the first step of sugar metabolism), respectively.^1,53 Since this glycolysis is necessary for the fermentation of sugar into lactic acid – the process cancer cells so love to use to fuel rapid growth –, inhibiting key enzymes along its path are a powerful tool if not in fully stopping cancer growth then at least in slowing it.

This already counts toward Aim 2. By slowing cancer growth we quite immediately extend patient life span, for the slower cancer grows, the longer it takes to reach lethal mass. Furthermore, inhibiting the specific process of lactic acid fermentation, leads to a lower acidity of the tumour microenvironment. Since cancer cells use acidity to enable and support invasion, metastasis, and immune evasion, less acidity means fewer and less severe painful metastases and a higher rate of immunological killing of cancer cells.^54–56 Furthermore, lower acidity also leads to slower cancer evolution by destabilising the genome less.⁵⁷

But dandelion also inhibits the synthesis of phosphatidylcholines and modulates glycerophospholipid metabolism.¹ Both of these compound classes are essential for proper membrane function.^58–60 Thus, if cancer cells want to grow rapidly, they need to synthesise components from these compound classes at sufficient rates to support the generation of new and functional cell membranes for their daughter cells to form and function properly.

And again, we see, that this – similarly to the disruption of glycolysis – helps us achieve Aim 2. The mechanism is the same as with glycolytic disruption, namely the simple and direct slowing of cancer cell proliferation, whereby the growth of cancerous tumours is slowed, and the life span of the patient immediately extended.

Furthermore, there are other compounds, which have been shown to modulate sugar metabolism. Some notable examples include oxamate and DCA.^43,61 It is not expected, that glycolytic modulation is enough to prevent or cure cancer. Thus, using a combination of compounds and therapeutic vectors is as always to be considered wise.

Considerations around Safety, Efficacy, and Dosage

In order to be able to make use of the beneficial effects of dandelion, we must consider the safety of its compounds and extracts. We must also look at which form of dandelion-derived extracts gives us the largest therapeutic window – meaning how can we get the most on-target effects for the least risk of adverse effects.

All of our following deliberations shall presume, the patient to not be allergic to dandelion and its compounds. This caveat is important, as allergic reactions are quite possible, given presence of sesquiterpene lactones.⁶² Due to the issue of potential allergy, use of dandelion should never commence at full effective dose, but be ramped up from zero over weeks. If allergic reaction occurs during ramp-up, use of dandelion should be suspended.

In one study of mice, a daily dose of 40 mg/kg of body weight showed no adverse effects on weight or tissues of the liver, kidney, and heart, whilst dandelion root extract was highly effective at reducing tumour volume increase, which was reduced by 90% in comparison with control.⁶³ This means, that administration of dandelion root extract is expected to show its multitude of effects at doses below toxicity, which in turn means, that its use can be safe and effective in patients.

Now, how does dosing look in humans? The experiments in mice may give us confirmation of a usable therapeutic window, where dandelion root extracts are effective, but still safe, but mouse dosages don't necessarily translate to human ones.

It's known, that traditional usage of dandelion is safe in all known cases, as no toxicity has ever been reported in humans.⁶² Such traditional doses are on average:

• 3–4 g powdered drug thrice a day.
• 0.75–1 g of 4:1 dry extract once a day.
• 5–10 mL of 1:5 tincture in 45% ethanol thrice a day.

In adults, a dosage of 4–10 g of powdered drug or as an aqueous infusion – basically, a tea with chopped or powdered dandelion – thrice a day is also considered safe.⁶² If you should buy dandelion extracts, the strength of the extract is important to consider.

Hereby, 4–10 g of 1:1 extract would be equivalent to 400–1,000 mg of 10:1 extract or 200–500 mg of 20:1 extract. Powered root extract can be obtained from Prescribed for Life, for example (no affiliation), though this powered root extract isn't the radix cum herba (root with leaves) application specified in [62]. It's not known, whether root extracts have the same toxic doses as root with leaves extracts, though it would be expected to lie in the same ballpark. In any case, do not exceed a daily dose of 12–30 g of crude dandelion, or the equivalent 1.2–3 g of 10:1 extract or 0.6–1.5 g of 20:1 extract.

Closing Remarks

With that we've come to the end of this fascinating journey of discovery. As you've just seen, dandelion can be quite the potent and safe ally in achieving our three aims of improving your quality of life, extending your duration of life, and improving your chance of cure.

I also think it's become obvious, that though potent, dandelion, its extracts, and their compounds, in no way resemble a cure for cancer. It's thus highly recommendable to use dandelion as only part of a larger interventionary plan to achieve the three Aims and get you more high-quality time with your loved ones.

If you want help with expanding your interventionary efforts to reclaim your life from the clutches of cancer, don't hesitate to reach out to us under www.marchward.com/reclaim. We mayn't be able to cure you, but we can give you a bit longer of a better life.

Swift healing and lasting health to you.

God bless,
Merlin L. Marquard