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.
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.
These 3 main metabolic fuel pathways exploited by Tumors 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.
MFIS Items – Metabolic Fuel Inhibition Strategy
Take 2-3 capsules with a little BIOFUZE™ in water 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 180 capsule versions may be more suitable for this. For synthetic chemotherapeutic versions consider: METFORMIN, LD/ASPIRIN and/or STATIN, NICLOSAMIDE, DIPYRIDAMOLE & MILDRONATE . BIOFUZE™ increases the absorption of this supplement into the cells improving efficiency. Increase the dosage and frequency if you are at a later stage in your condition.
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 [9, 30, 38]. 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 [1, 2] .
Adverse effects of niclosamide are mild and infrequent. This may include GI disturbances, light-headedness, malaise, and pruritus. [source] Alcohol or DMSO (BIOFUZE™) may enhance the absorption of niclosamide, but also could increase the risk of side effects at higher Niclosamide levels .
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/
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].
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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.
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Multi-targeted therapy of cancer by niclosamide: a new application for an old drug
Mitochondrial metabolism and cancer
Targeting mitochondria as an anti-tumor strategy
Olive Leaf , Ginger & Green Tea reduce Aerobic Glycolysis
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