NICLOSTEM™ – CSC-Targeting Double-Hit Formula

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NICLOSTEM™ is a capsule formula containing three ingredients shown to reduce mitochondrial fuel to Tumor Stem Cells (CSC’s) containing Niclosamide, Silimarin, Olive Leaf Extract , Shitake, Coriolus, Ginger and Broccoli Sprout Extract.

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Description

In order to get off the chemotherapy merri-go-round, we must learn about non-toxic targeted therapies which can kill tumor stem cells (CSC’s). Some of these therapies are supplements at the health food store, and some are long-proven safe chemicals such as Niclosamide. With knowledge of Targeting Tumor Stem Cells with Non Toxic targeted therapies, a durable remission after the last chemotherapy treatment might be achieved.

Mitochondria are organelles controlling adenosine triphosphate (ATP) energy generation, redox homeostasis, metabolic signaling, and apoptotic pathways. Although glycolysis was traditionally considered as the major source of energy in tumor cells, in-line with the so-called “Warburg effect”, mitochondria have been recognised to play a key role in oncogenesis [source]. Tumor cells uniquely reprogram their cellular activities to support their rapid proliferation and migration, as well as to counteract metabolic and genotoxic stress during progression [source].

Further, mitochondria can switch their metabolic phenotypes to meet the challenges of high energy demand and macromolecular synthesis [source]. Thus, tumor mitochondria have the ability to flexibly switching between glycolysis and oxidative phosphorylation (OXPHOS) for their survival. [source]

By targeting these two main fuels known as a Double-Hit approach, we have developed NICLOSTEM™ which includes a number of ingredients such as Ginger, Silimarin, Olive Leaf Extract and Sulforaphane from Broccoli Sprout extract  which are shown to inhibit key metabolic processes such as OXPHOS, Glycolysis, WNT and HDAC , which when combined with Glutamine and Fatty Acid Inhibitors should cause fuel starvation and stress to CSC’s.  The additional inclusion of mushrooms Shitake and Coriolus (Turkey Tail) could help to improve T Cell immune response.

Some of the  Tumor Stem Cell-related gene pathways are:
WNT/B-catenin, Notch, SHH, HKII, CD44, Cyclin D1, OXPHOS, Aerobic Glycolysis 

 

NICLOSTEM™ is a capsule formula containing seven ingredients shown to reduce mitochondrial fuel to Tumor Stem Cells (CSC’s) containing Niclosamide, Silimarin, Olive Leaf Extract , Shitake, Coriolus, Ginger and Broccoli Sprout Extract.


View Labtests. Niclosamide (99.2%), Silimarin (80.7%).



CSC Double-Hit Strategy

It has been shown that he prolonged treatment with a mitochondria-interfering agent like doxycycline drastically impairs OCR and mitochondrial respiration in breast cancer cells. Such impairment in mitochondrial activity represents a first metabolic hit that constrains cellular metabolism toward glycolysis, as evidenced by the increased extracellular acidification rate (ECAR). The use of a glycolysis inhibitor may therefore act a second metabolic hit that efficiently targets CSCs by halting their biochemical machinery. This approach reverses CSC metabolic plasticity toward an inflexible biochemical phenotype that can be efficiently targeted with specific metabolic-oriented pharmacological intervention. [source]

NICLOSTEM™ may be used as an adjuvant to standard care, and as part of a metabolic fuel-blocking approach along with FASNHIB™, GLUTAHIB™  to inhibit metabolic fuel supply and also with MEBENGRAV™ to activate caspases  for the kill phase of the same strategy illucidated in the book by Jane McLelland (below).

These 3 main metabolic fuel pathways exploited by Tumors are the subject of Jane McLelland’s superb book: ‘How to Starve Cancer’ , where Jane shares her strategy for using Re-purposed drugs such as Metformin, Doxycyline, Dipyridamole,  Niclosamide, Aspirin and a statin to target and inhibit these pathways which drive the TCA cycle within each Tumor cell with the aim of to weakening it over time. MBZ also interferes with VEGF kinase by competing with ATP which is the energy used within the TCA Cycle of every cell.

 

 

Biohackit Neutraceuticals Range Buy FASNHIB Buy GLUTAHIB Buy Metastahib Buy Myelomhib Buy VBLOCK Buy SARCOMHIB Buy MEBENGRAV Buy AUTOPHIB Buy BCHIB Buy Mebencur Buy Fenbencide Cream Image Map

Ingredients:

NICLOSTEM™ Ingredients per 2x Vegan Capsules
Niclosamide (5‐chlorosalicylic acid) (†) 300mg *
Olive Leaf Extract (20% oleuropein)(†) 100mg *
Broccoli Sprout 10:1 Extract (†) 1000mg *
Ginger 5:1 Extract (†) 300mg *
Silimarin 40:1 Extract (†) 4000mg *
Shitake Mushroom(†) 100mg *
Coriolus (Turkey Tail) Mushroom (†) 100mg *
Other ingredients: HPMC Hypromellose (vegetable capsule), zero fillers, (†) Lab-Tested, * Daily value not established

Suggested Usage

Take 2-3 capsules with a little alcohol 3x/day after food or as directed by a health professional. May be suitable as an adjuvant.  NICLOSTEM™ may best be supported with  FASNHIB™ for Fatty Acid inhibition  & GLUTAHIB™ metabolic fuel supply inhibiting formulas,  CURCUBOS™,  CURCUMEL™,  EGAMMA™, OMEGA DHA™, and a ZERO Sugar/Fat Diet with regular cruciferous vegetables (SULFORAPHANE).  The 120 or 180 capsule versions may be more suitable for this. For synthetic chemotherapeutic versions consider: METFORMIN, LD/ASPIRIN and/or STATIN, NICLOSAMIDE, DIPYRIDAMOLE & MILDRONATE and refer to Jane McLelland’s book: ‘How to Starve Cancer’ .

Niclosamide Safety

Niclosamide has been proven to be without effect on hematological and urinalysis parameters and not to influence liver and kidney function tests []. Recent studies have also indicated that no significant toxicity was shown against non-tumor cells in vitro and no obvious side effects were observed in niclosamide-treated mice []. The fate of niclosamide in humans, which closely resembles that in animals, and the low acute toxicity in humans and animals suggest that even a prolonged contact with niclosamide will not result in cumulative toxic effects in humans []. However, niclosamide is poorly absorbed from the intestinal tract, which explains its good tolerability in humans [] .
Adverse effects of niclosamide are mild and infrequent. This may include GI disturbances, light-headedness, malaise, and pruritus. [source]  Alcohol may enhance the absorption of niclosamide, but also could increase the risk of side effects at higher levels and therefore should be kept only to a very small amount to increase the bioavailability of Niclosamide. Niclosamide is safe for use in pregnancy. It is thought that Niclosamide can be better absorbed when take with a little alcohol.

Drug Interactions
:  Drug interactions may occur with Fenbendazole if salicylanilides such as niclosamide are co-administered. Abortions in cattle and death in sheep have been reported after using these medications together. [source: Plumb’s Veterinary Drug Handbook, Fifth Edition, 2005 ] Abortions in domestic ruminants have been associated with concurrent use of anti-trematode therapeutic agents. https://www.cancertreatmentsresearch.com/fenbendazole/

Dosage Limits
Niclosamide is commonly used  as a single dose of 2g for Tapeworm infections ; in a child younger than 2 years, 500mg; and if 2 to 6 years of age, 1g [source], however, it is thought that lower dosages might be applicable for daily long term usage. Niclosamide downregulated several stem cell signaling pathways including the Wnt/ß-catenin, Notch, and Hedgehog pathways, inhibited the formation of spheroids, and induced apoptosis in breast cancer stem-like cells CD44/CD24  [source]. Animal studies also confirmed this therapeutic effect [source]. Using a similar approach, the same group further demonstrated that niclosamide was an inhibitor of stem-like ovarian-cancer-initiating cells, and suppressed the tumor formation of ovarian-cancer-initiating cells in vivo [source]. Moreover, it was reported that niclosamide was effective in killing acute myeloid leukemia (AML) stem cells (CD34+CD38-), but had minimal cytotoxicity against progenitor cells in normal bone marrow [source].

 

Quality Assurance Declaration

Lab-Tested
Werone.co endeavors to use the most potent source materials within our formulas. Our herbal extracts are sourced and tested by the only Government-certified large scale producer of crude herb (powder-free) TCM concentrates in Asia who manufacture to GMP / ISO 9001/2000 pharmaceutical grade and also operate an ISO17025/TAF-certified laboratory where they subject all plant extracts to strict quality inspections free from heavy metals, pesticides or microbes before release to the clinics all over the world. The formulas and tinctures are assembled without fillers in small batches by a BHMA member herbal dispensary.

 

Nutraceutical Disclaimer

These statements have not been evaluated by the Food and Drug Administration or MHRA and the items are not intended to diagnose, treat, cure, or prevent any disease nor are they associated, endorsed, affiliated or sponsored by Anthony William, Medical Medium® Joe Tippens or Jim Gordon.

 

Clinical References

Multi-targeted therapy of cancer by niclosamide: a new application for an old drug
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4166407/

Mitochondrial metabolism and cancer
https://www.nature.com/articles/cr2017155

Targeting mitochondria as an anti-tumor strategy
https://cancercommun.biomedcentral.com/articles/10.1186/s40880-019-0412-6

Olive Leaf , Ginger & Green Tea reduce Aerobic Glycolysis

Natural Compounds that Slow Glycolysis in Cancers – Part 2

Liu et al. recently demonstrated that a subpopulation of cells with stem-like properties mainly rely on glucose as a primary fuel. Indeed, glucose was able to increase
the number of cancer stem-like cells, in which many glycolytic enzymes were up-regulated and lactate production was elevated. Likewise, the inhibition of glycolysis was shown to reduce the number of CSCs and interfere with their tumor-forming ability in vivo [https://www.nature.com/articles/cdd2013131 ]

Cancer stem cells (CSCs): metabolic strategies for their identification and eradication
https://portlandpress.com/biochemj/article/475/9/1611/49910/Cancer-stem-cells-CSCs-metabolic-strategies-for

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