VIT C and Cancer STEM cells

Dr. Weeks’ Comment:   Many natural agents are effective at remedying cancer STEM cells – the real target for people fighting cancer – and now vitamin C is validated again. Other natural remedies include  Bee venom derivative CAPE  cafeic acid phenyl ester  as well as vitamin D3 and melatonin See this lecture Strike the Root – Remedy the Cancer STEM cells  to understand more about the critical importance of targeting cancer STEM cells and not cancer TUMOR cells.

 

Vitamin C effective in targeting cancer stem cells

Thursday 9 March 2017

VITAMIN C is up to ten times more effective at stopping cancer cell growth than pharmaceuticals such as 2-DG, according to scientists in Salford, UK.

The research, published in Oncotarget, is the first evidence that Vitamin C (ascorbic acid) can be used to target and kill cancer stem cells (CSCs), the cells responsible for fuelling fatal tumours.

Dr. Michael P. Lisanti, Professor of Translational Medicine at the University of Salford, said: “We have been looking at how to target cancer stem cells with a range of natural substances including silibinin (milk thistle) and CAPE, a honey-bee derivative, but by far the most exciting are the results with Vitamin C.

“Vitamin C is cheap, natural, non-toxic and readily available so to have it as a potential weapon in the fight against cancer would be a significant step.”

Seven substances

Cancer stem-like cells are thought to be the root cause of chemotherapy resistance, leading to treatment failure in patients with advanced disease and the triggers of tumour recurrence and metastasis (regrowth).

The Salford team set out to assess the bioenergetics of cancer stem cells – the processes which allow the cells to live and thrive – with a view to disrupting their metabolism.

Focusing on energy-transfer, they measured the impact on cell lines in a laboratory of 7 substances, the clinically-approved drug stiripentol, 3 natural products – caffeic acid phenyl ester (CAPE), silibinin and ascorbic acid – and experimental pharmaceuticals, such as actinonin, FK866 and 2-DG.

While they found that natural antibiotic actinonin and the compound FK866 were the most potent, the natural products also inhibited CSC formation, with Vitamin C, outperforming 2-DG by tenfold in terms of potency.

Evidence growing

Vitamin C has previously been shown to be effective as a non-toxic anti-cancer agent in studies by Nobel Prize winner Linus Pauling and was recently shown to reduce mortality by 25% on breast cancer patients in Japan. However, its effects on CSC activity have not been previously evaluated and in this context, it behaves as an inhibitor of glycolysis, which fuels energy production in mitochondria, the “powerhouse” of the cell.

Dr Gloria Bonuccelli, lead author and another member of the Salford team added: “This is further evidence that Vitamin C and other non-toxic compounds may have a role to play in the fight against cancer.

“Our results indicate it is a promising agent for clinical trials, and a as an add-on to more conventional therapies, to prevent tumour recurrence, further disease progression and metastasis.”

 

THE ARTICLE  here:  http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=15400

Title:  NADH autofluorescence, a new metabolic biomarker for cancer stem cells: Identification of Vitamin C and CAPE as natural products targeting “stemness”.

Authors:  Gloria Bonuccelli, Ernestina Marianna De Francesco, Rianne de Boer, Herbert B. Tanowitz and Michael P. Lisanti.

ABSTRACT    Here, we assembled a broad molecular “tool-kit” to interrogate the role of metabolic heterogeneity in the propagation of cancer stem-like cells (CSCs). First, we subjected MCF7 cells to “metabolic fractionation” by flow cytometry, using fluorescent mitochondrial probes to detect PCG1α activity, as well ROS and hydrogen-peroxide (H2O2) production; NADH levels were also monitored by auto-fluorescence. Then, the various cell populations were functionally assessed for “stem cell activity”, using the mammosphere assay (3D-spheroids). Our results indicate that a sub-population of MCF7 cells, with increased PGC1α activity, high mitochondrial ROS/H2O2 production and high NADH levels, all form mammospheres with a higher efficiency. Thus, it appears that mitochondrial oxidative stress and the anti-oxidant response both contribute to the promotion of mitochondrial biogenesis and oxidative metabolism in CSCs. Further validation was provided by using specific inhibitors to target metabolic processes (the NAD+ salvage pathway, glycolysis, mitochondrial protein synthesis and OXPHOS), significantly reducing CSC propagation. As a consequence, we have now identified a variety of clinically-approved drugs (stiripentol), natural products (caffeic acid phenyl ester (CAPE), ascorbic acid, silibinin) and experimental pharmaceuticals (actinonin, FK866, 2-DG), that can be used to effectively inhibit CSC activity. We discuss the use of CAPE (derived from honey-bee propolis) and Vitamin C, as potential natural therapeutic modalities. In this context, Vitamin C was ~10 times more potent than 2-DG for the targeting of CSCs. Similarly, stiripentol was between 50 to 100 times more potent than 2-DG.

http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=15400

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