Glutamine is a major metabolic fuel for both brain tumor cells and tumor-associated macrophages (TAMs)
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The efficacy of licorice root extract in decre... [Phytother Res. 2012] - PubMed - NCBI - 0 views
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licorice licorice root extract NAFLD liver enzymes liver non-alcoholic fatty liver
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Everything You Need to Know About Root Canal Treatment - 1 views
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dental health healthcare and fitness
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Kava and valerian in the treatment of stress-induc... [Phytother Res. 2001] - PubMed re... - 0 views
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stress insomnia sleep Kava valerian root natural alternative therapy treatment
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Effect of valerian on sleep quality in postmenopau... [Menopause. 2011] - PubMed result - 0 views
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valerian root insomnia natural herb sleep alternative treatment therapy
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Licorice reduces serum testosterone in heal... [Steroids. 2004 Oct-Nov] - PubMed - NCBI - 0 views
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Long term administration of a licorice extract in the treatment of - 0 views
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licorice licorice root extract liver enzymes liver cirrhosis liver Hepatitis C HCV hepatitis
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The Diuretic Effect in Human Subjects of an Extract of Taraxacum officinale Folium over... - 0 views
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LeanBiome™ (Official) | Get Save UpTo $540 Today Only! - 0 views
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LeanBiome™ (Official) | Get Save UpTo $540 Today Only! usleanbiome.com LeanBiome™ Hurry Up! Offer Expires in: 00 HOUR 29 MINUTE 59 SECOND LeanBiome Attention! Get Special 84% Discount Today Faster fat burning and weight loss Healthy cholesterol and sugar levels Higher energy levels Regular price: $129 Only for: 39$ What Is LeanBiome? LeanBiome Lean for Good is a weight loss dietary supplement derived from scientifically researched ingredients and comprehensively developed to help people achieve sustainable weight control. The formula comes in a capsule format that is easy to take and is made with natural ingredients from plants and other sources to achieve its goals. The main ingredient in LeanBiome is piperine, which has been found to affect the body's ability to absorb micronutrients and other compounds more effectively. LeanBiome is a dietary supplement that claims to help weight management. It contains 100% natural ingredients that support healthy weight loss. It does not interfere with any natural process making it safe for use. It ranks among the top weight loss supplements that claim to provide a permanent solution. LeanBiome is made by a company named Lean for Good. It is made with natural and research-backed ingredients that help you lose excess fat without hassles. It is sold in capsule form. The company assures the composition is GMO, gluten, and soy-free. As for manufacturing standards, you need not fret. The company makes the supplement in a facility certified by the FDA. How Does LeanBiome Work? The starting period of the LeanBiome program includes a detoxification process that effectively removes any accumulated ree radicals, toxins, fand oxidative stress. This cleansing enables improved blood circulation, setting the stage for the body to initiate its own fat-burning mechanisms. To enhance metabolic activity, introducing the lean bacteria contained in LeanBiome to your gut microbiome is a beneficial approach. This activation triggers r
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New PROTI 360° Family of Implants to Enhance Spinal Fusion Surgery India - 10... - 0 views
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Affordable spinal fusion surgery hospital India spinal fusion surgery India Low cost Hospital
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About 400,000 sufferers undergo spinal fusion surgery India annually to help lessen pain and nerve root infection in India alone. During this method, a disc is eliminated and an interbody spacer is implanted to doubtlessly restore natural height between two vertebrae and create solid bone. International Helpline Number : +91-9325887033 Email Id: enquiry@spineandneurosurgeryhospitalindia.com
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Metabolic management of brain cancer - 0 views
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the malignant phenotype of brain tumor cells that survive radiotherapy is often greater than that of the cells from the original tumor.
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Conventional chemotherapy has faired little better than radiation therapy for the long-term management of malignant brain cancer
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most conventional radiation and brain cancer chemotherapies can enhance glioma energy metabolism and invasive properties, which would contribute to tumor recurrence and reduced patient survival [34].
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We contend that all cancer regardless of tissue or cellular origin is a disease of abnormal energy metabolism
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complex disease phenotypes can be managed through self-organizing networks that display system wide dynamics involving oxidative and non-oxidative (substrate level) phosphorylation
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As long as brain tumors are provided a physiological environment conducive for their energy needs they will survive; when this environment is restricted or abruptly changed they will either grow slower, growth arrest, or perish [8] and [19]
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New information also suggests that ketones are toxic to some human tumor cells and that ketones and ketogenic diets might restrict availability of glutamine to tumor cells [68], [69] and [70].
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The success in dealing with environmental stress and disease is therefore dependent on the integrated action of all cells in the organism
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Tumor cells survive in hypoxic environments not because they have inherited genes making them more fit or adaptable than normal cells, but because they have damaged mitochondria and have thus acquired the ability to derive energy largely through substrate level phosphorylation
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Cancer cells survive and multiply only in physiological environments that provide fuels (mostly glucose and glutamine) subserving their requirement for substrate level phosphorylation
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Integrity of the inner mitochondrial membrane is necessary for ketone body metabolism since β-hydroxybutyrate dehydrogenase, which catalyzes the first step in the metabolism of β-OHB to acetoacetate, interacts with cardiolipin and other phospholipids in the inner membrane
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Any genetic or environmental alteration in the content or composition of cardiolipin will compromise energy production through oxidative phosphorylation
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the Crabtree effect can be reversible, the Warburg effect is largely irreversible because its origin is with permanently damaged mitochondria
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The continued production of lactic acid in the presence of oxygen is the metabolic hallmark of most cancers and is referred to as aerobic glycolysis or the Warburg effect
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We recently described how the retrograde signaling system could induce changes in oncogenes and tumor suppressor genes to facilitate tumor cell survival following mitochondrial damage [48].
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In addition to glycolysis, glutamine can also increase ATP production under hypoxic conditions through substrate level phosphorylation in the TCA cycle after its metabolism to α-ketoglutarate
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mitochondrial lipid abnormalities, which alter electron transport activities, can account in large part for the Warburg effect
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targeting both glucose and glutamine metabolism could be effective for managing most cancers including brain cancer
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The bulk of experimental evidence indicates that mitochondria are dysfunctional in tumors and incapable of generating sufficient ATP through oxidative phosphorylation
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Cardiolipin defects in tumor cells are also associated with reduced activities of several enzymes of the mitochondrial electron transport chain making it unlikely that tumor cells with cardiolipin abnormalities can generate adequate energy through oxidative phosphorylation
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TCA cycle substrate level phosphorylation could therefore become another source of ATP production in tumor cells with impairments in oxidative phosphorylation
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Caloric restriction, which lowers glucose and elevates ketone bodies [63] and [64], improves mitochondrial respiratory function and glutathione redox state in normal cells
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DR naturally inhibits glycolysis and tumor growth by lowering circulating glucose levels, while at the same time, enhancing the health and vitality of normal cells and tissues through ketone body metabolism
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We suggest that apoptosis resistance arises largely from enhanced substrate level phosphorylation of tumor cells and to the genes associated with elevated glycolysis and glutaminolysis, e.g., c-Myc, Hif-1a, etc, which inhibit apoptosis
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Modern medicine has not looked favorably on diet therapies for managing complex diseases especially when well-established procedures for acceptable clinical practice are available, regardless of how ineffective these procedures might be in managing the disease
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More than 60 years of clinical research indicates that such approaches are largely ineffective in extending survival or improving quality of life
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The process is rooted in the well-established scientific principle that tumor cells are largely dependent on substrate level phosphorylation for their survival and growth
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targeting the glycolytically active tumor cells that produce pro-cachexia molecules, restricted diet therapies can potentially reduce tumor cachexia
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Blood glucose ranges between 3.0 and 3.5 mM (55–65 mg/dl) and β-OHB ranges between 4 and 7 mM should be effective for tumor management
Excellent Chiropractic Services - 1 views
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Licorice abuse: time to send a warning message - 0 views
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shared by Nathan Goodyear on 09 Mar 15
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Effect of Tongkat Ali on stress hormones and psychological mood state in moderately str... - 0 views
www.ncbi.nlm.nih.gov/...PMC3669033
Tongkat Ali long jack cortisol stress testosterone hormone hormones
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Eurycoma contains a group of small peptides referred to as “eurypeptides” that are known to have effects in improving energy status and sex drive in studies of rodents
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The effects of tongkat ali in restoring normal testosterone levels appears to be less due to actually “stimulating” testosterone synthesis, but rather by increasing the release rate of “free” testosterone from its binding hormone, sex-hormone-binding-globulin (SHBG)
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The current study found that daily supplementation with tongkat ali root extract (200 mg/day) improves stress hormone profile (lower cortisol; higher testosterone) and certain mood state parameters (lower tension, anger, and confusion)
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tongkat ali supplementation (100 mg/day) improved lean body mass, 1-RM strength, and arm circumference to a significantly greater degree compared to a placebo group.
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In a recent 12-week trial [46] of Eurycoma longifolia supplementation (300 mg/day), men (30–55 years of age) showed significant improved compared to placebo in the Physical Functioning domain of the SF-36 quality of life survey
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In men with low testosterone levels (average age 51 years), one month of daily supplementation with tongkat ali extract (200 mg/day) resulted in a significant improvement in serum testosterone levels and quality-of-life parameters
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Laser Hair Removal in Dubai - 1 views
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hairremoval hair laser in Dubai UAE health Beauty healthCare
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The reason why laser hair removal in Dubai has gained such outstanding popularity is because it's the least invasive and safe cosmetic procedure used to permanently remove unneeded body hair. With focused laser energy directed at the hair roots, melanin in the hair follicles is broken down hence preventing hair from growing permanently.
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The special extract ERr 731 of the roots o... [Menopause. 2007 Mar-Apr] - PubMed - NCBI - 0 views
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Obesity In Children And Teens | American Academy of Child & Adolescent Psychiatry - 0 views
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Mitochondrial Fission Induces Glycolytic Reprogramming in Cancer-Associated Myofibrobla... - 0 views
www.ncbi.nlm.nih.gov/...PMC3478457
warburg effect Cancer cancer associated fibroblasts CAFs reverse warburg effect lactate aerobic glycolysis mitochondria oxidative stress ROS H2O2
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L-lactate functions as an onco-metabolite, stimulating mitochondrial biogenesis and OXPHOS in adjacent cancer cells, directly providing energy for tumor growth
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Oxidative stress in stromal fibroblasts then induces their metabolic conversion into cancer-associated fibroblasts. Such oxidative stress drives the onset of autophagy, mitophagy, and aerobic glycolysis in fibroblasts, resulting in the local production of high-energy mitochondrial fuels (such as L-lactate, ketone bodies, and glutamine). These recycled nutrients are then transferred to cancer cells, where they are efficiently burned via oxidative mitochondrial metabolism (OXPHOS)
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stromal L-lactate serves as a high-energy mitochondrial “fuel” for cancer cells. We have termed this new model of cancer metabolism “Two-Compartment Tumor Metabolism”, where two opposing metabolic compartments co-exist, side-by-side, with stromal glycolysis fueling OXPHOS in cancer cells
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Reverse Warburg Effect”, is that catabolic fibroblasts should promote tumor growth, without any increases in angiogenesis
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when cancer cells use L-lactate as a mitochondrial fuel source, this metabolic phenotype is a predictor of lethal cancer metabolism
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mitochondrial dysregulation is likely the “root cause” of several human disease(s), and especially epithelial cancers
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Both in vitro and in vivo studies have now provided convincing evidence that “activated” stromal fibroblasts, a.k.a., myofibroblasts, may play a critical role in initiating tumor recurrence, via paracrine interactions with adjacent tumor epithelial cells
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A new hypothesis is that cancer is not a cell autonomous disease, but rather a disease of the tumor microenvironment
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cancer cells behave as metabolic parasites, by inducing oxidative stress in adjacent normal fibroblasts
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recent experimental evidence indicates that cancer-associated fibroblasts have a catabolic phenotype, and undergo autophagy and mitophagy, resulting in the onset of glycolytic metabolism, driving L-lactate production, and its release into the tumor microenvironment
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oncogenic mutations in cancer cells lead to ROS production and the “secretion” of hydrogen peroxide species
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A good discussion of what is proposed the Reverse Warburg effect. A process by which the local environment dictates tumor progression. The cancer cells release ROS primarily in the form of H2O2 and this leads to Cancer Associated Fibroblasts (CAFs) in the stroma. The altered stromal environment increases ROS further and promotes ocogenic metabolites through the classic Warburg effect. This high lactate production from the CAFs then is used by the cancer cells via classic oxidative phosphorylation. Complex, beautiful and still an the understanding is a work in progress. This study/article points to the importance of oxidative stress in some cancer development through CAFs.
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Oncotarget | Vitamin C and Doxycycline: A synthetic lethal combination therapy targetin... - 0 views
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These eight distinct cancer types included: DCIS, breast (ER(+) and ER(-)), ovarian, prostate, lung, and pancreatic carcinomas, as well as melanoma and glioblastoma. Doxycycline was also effective in halting the propagation of primary cultures of CSCs from breast cancer patients, with advanced metastatic disease (isolated from ascites fluid and/or pleural effusions)
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Doxycycline behaves as a strong radio-sensitizer, successfully overcoming radio-resistance in breast CSCs
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cancer cells can indeed escape the effects of Doxycycline, by reverting to a purely glycolytic phenotype. Fortunately, the metabolic inflexibility conferred by this escape mechanism allows Doxycycline-resistant (DoxyR) CSCs to be more effectively targeted with many other metabolic inhibitors, including Vitamin C, which functionally blocks aerobic glycolysis
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Vitamin C inhibits GAPDH (a glycolytic enzyme) and depletes the cellular pool of glutathione, resulting in high ROS production and oxidative stress
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Doxycycline and Vitamin C may represent a new synthetic lethal drug combination for eradicating CSCs, by ultimately targeting both mitochondrial and glycolytic metabolism
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metabolic flexibility in cancer cells allows them to escape therapeutic eradication, leading to chemo- and radio-resistance
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used doxycycline to pharmacologically induce metabolic inflexibility in CSCs, by chronically inhibiting mitochondrial biogenesis
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Cancer stem cells (CSCs) are thought to be the “root cause” of tumor recurrence, distant metastasis and therapy-resistance
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the conserved evolutionary similarities between aerobic bacteria and mitochondria, certain classes of antibiotics inhibit mitochondrial protein translation, as an off-target side-effect
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Vitamin C was more potent than 2-DG; it inhibited DoxyR CSC propagation by > 90% at 250 µM and 100% at 500 µM
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treatment with Berberine effectively inhibited the propagation of the DoxyR CSCs by > 50% at 1 µM and > 80% at 10 µM.
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Doxycycline, a clinically approved antibiotic, induces metabolic stress in cancer cells. This allows the remaining cancer cells to be synchronized towards a purely glycolytic phenotype, driving a form of metabolic inflexibility
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new synthetic lethal strategy for eradicating CSCs, by employing i) Doxycycline (to target mitochondria) and ii) Vitamin C (to target glycolysis)
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a metabolic shift from oxidative to glycolytic metabolism represents an escape mechanism for breast cancer cells chronically-treated with a mitochondrial stressor like Doxycycline, as mitochondrial dys-function leads to a stronger dependence on glucose
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Vitamin C has been demonstrated to selectively kill cancer cells in vitro and to inhibit tumor growth in experimental mouse models
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many of these actions have been attributed to the ability of Vitamin C to act as a glycolysis inhibitor, by targeting GAPDH and depleting the NAD pool
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here we show that DoxyR CSCs are more vulnerable to the inhibitory effects of Vitamin C, at 4- to 10-fold lower concentrations, between 100 to 250 μM
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concurrent use of Vitamin C, with standard chemotherapy, reduces tumor recurrence and patient mortality
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pro-oxidant activity results from Vitamin C’s action on metal ions, which generates free radicals and hydrogen peroxide, and is associated with cell toxicity
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This selectivity appears to be due to the higher catalase content observed in normal cells (~10-100 fold greater), as compared to tumor cells. Hence, Vitamin C may be regarded as a safe agent that selectively targets cancer cells
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the concurrent use of Doxycycline and Vitamin C, in the context of this infectious disease, appeared to be highly synergistic in patients
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Goc et al., 2016, showed that Doxycycline is synergistic in vitro with certain phytochemicals and micronutrients, including Vitamin C, in the in vitro killing of the vegetative spirochete form of Borrelia spp., the causative agent underlying Lyme disease
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Doxycycline, an FDA-approved antibiotic, behaves as an inhibitor of mitochondrial protein translation
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CSCs successfully escape from the anti-mitochondrial effects of Doxycycline, by assuming a purely glycolytic phenotype. Therefore, DoxyR CSCs are then more susceptible to other metabolic perturbations, because of their metabolic inflexibility
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shared by Nathan Goodyear on 08 Dec 17
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Oncotarget | NADH autofluorescence, a new metabolic biomarker for cancer stem cells: Id... - 0 views
www.oncotarget.com/index.php
vitamin C IV vitamin C cancer cancer stem cells milk thistle silymarin ascorbic acid bee propolis CAPE glycolytic inhibitor natural
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Cancer stem-like cells (CSCs) are thought to be the root cause of chemotherapy-resistance and radio-resistance
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ultimately leading to treatment failure in patients with advanced disease [1-3]. They have been directly implicated mechanistically in tumor recurrence and metastasis, resulting in poor patient survival
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Our results indicate that increased mitochondrial oxidative stress and high NADH levels are both key characteristics of the CSC metabolic phenotype
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high levels of NAD(P)H auto-fluorescence are known to be a surrogate marker for mitochondrial “power”, high OXPHOS capacity and increased ATP production
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an intact NAD+ salvage pathway is strictly required for mammosphere formation, supporting our results using NAD(P)H auto-fluorescence, which enriched CSC activity by more than 5-fold.
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Since glycolysis is especially critical for maintaining the TCA cycle, OXPHOS and overall mitochondrial function, we next assessed the effects of known glycolytic inhibitors
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we show that two other natural products that function as effective glycolysis inhibitors, also inhibited mammosphere formation. More specifically, vitamin C (ascorbic acid), which induces oxidative stress and inhibits the activity of GAPDH (a key glycolytic enzyme) [17], also inhibited mammosphere formation, with an IC-50 of 1 mM (Figure 7B). Therefore, vitamin C was ~10 times more potent than 2-DG at targeting CSC propagation
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silibinin (the major active constituent of silymarin, an extract of milk thistle seeds) [18], which specifically functions as an inhibitor of glucose uptake, blocked mammosphere formation, with an IC-50 between 200 and 400 µM
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caffeic acid phenyl ester (CAPE), a key component of honey-bee propolis, has potent anti-cancer properties
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Because of it aromatic ring structure (Figure 8), we speculated that CAPE might function as a potent inhibitor of oxidative mitochondrial metabolism
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CAPE quantitatively inhibits the mitochondrial oxygen consumption rate (OCR) and, in turn, induces the onset of aerobic glycolysis (ECAR)
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CAPE shows a clear selectivity for targeting CSCs and adherent cancer cells, relative to normal fibroblasts.
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CAPE functions as a “natural” mitochondrial OXPHOS inhibitor, that preferentially targets the CSC sub-population. This could explain CAPE’s known anti-cancer properties
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Our data directly shows that a small fraction of the total cell population, characterized by increased PGC1α activity, high mitochondrial ROS/H2O2 and high NADH levels, has the ability to survive and grow under anchorage-independent conditions, driving mammosphere formation
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We highlight the utility of certain natural products, such as Silibinin, Vitamin C and CAPE, that could be used to therapeutically target CSCs. Silibinin is the major active component of silymarin, which is an extract prepared from milk thistle seeds.
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Previous studies have also shown that when non-CSCs and CSCs are both fed mitochondrial fuels (such as L-lactate or ketone bodies), that CSCs quantitatively produce more NADH in response to this stimulus
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The Noble Prize winner, Linus Pauling, was among the first to describe and clinically test the efficacy of Vitamin C, as a relatively non-toxic anti-cancer agent
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Vitamin C has two mechanisms of action. First, it is a potent pro-oxidant, that actively depletes the reduced glutathione pool, leading to cellular oxidative stress and apoptosis in cancer cells. Moreover, it also behaves as an inhibitor of glycolysis, by targeting the activity of GAPDH, a key glycolytic enzyme.
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Here, we show that Vitamin C can also be used to target the CSC population, as it is an inhibitor of energy metabolism that feeds into the mitochondrial TCA cycle and OXPHOS
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Vitamin C may prove to be promising agent for new clinical trials, aimed at testing its ability to reduce CSC activity in cancer patients, as an add-on to more conventional therapies, to prevent tumor recurrence, further disease progression and metastasis
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Interestingly, a breast cancer based clinical study has already shown that the use of Vitamin C, concurrent with or within 6 months of chemotherapy, significantly reduces both tumor recurrence and patient mortality
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CAPE quantitatively reduces mitochondrial oxygen consumption (OCR), while inducing a reactive increase in glycolysis (ECAR). As such, it potently inhibits mammosphere formation with an IC-50 of ~2.5 µM. Similarly, it also significantly inhibits cell migration
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we also demonstrate that 7 different inhibitors of key energetic pathways can be used to effectively block CSC propagation, including three natural products (silibinin, ascorbic acid and CAPE). Future studies will be necessary to test their potential for clinical benefit in cancer patients.
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The future of cancer therapy is cancer stem cells. Study finds that Vitamin C, silymarin, and bee propolis blocks mitochondrial energy pathways in cancer stem cells. Vitamin C is a known glycolytic inhbitor. Vitamin C was found to inhibit glycolysis via GAPDH targeting to inhibit the energy pathways of the mitochondria in CSCs. The authors propse that Vitamin C can be used as add on therapies for conventional therapies to specifically attack the CSCs and their contribution to recrurence, treatment resistance, and metastasis potential all in addition to the ability of vitamin C to reduce the side effects of chemotherapy.