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Nathan Goodyear

Home: Cell PressInhibition of Amino Acid Metabolism Selectively Targets Human Leukemia ... - 0 views

www.cell.com/...S1535-6108(18)30471-9

Cancer cancer stem cells CSC

shared by Nathan Goodyear on 24 Nov 18 - No Cached
  • Nathan Goodyear on 24 Nov 18
     
    Cancer Stem cells are not tied to the Warburg effect.
Nathan Goodyear

BCL-2 inhibition targets oxidative phosphorylation and selectively eradicates quiescent... - 0 views

www.ncbi.nlm.nih.gov/...PMC3595363

CSC cancer stem cells leukemia oxidative phosphorylation cancer

shared by Nathan Goodyear on 28 Nov 18 - No Cached
  • Nathan Goodyear on 28 Nov 18
     
    Leukemia stem cells use oxidative phosphorylation metabolism via upregulation of bcl-2 gene.
Nathan Goodyear

Oncotarget | Vitamin C and Doxycycline: A synthetic lethal combination therapy targetin... - 0 views

www.impactjournals.com/...index.php

cancer doxycycline IV vitamin C vitamin C

shared by Nathan Goodyear on 14 Jun 17 - No Cached
  • 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)
  • Doxycycline behaves as a strong radio-sensitizer, successfully overcoming radio-resistance in breast CSCs
  • 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
  • ...36 more annotations...
  • Vitamin C inhibits GAPDH (a glycolytic enzyme) and depletes the cellular pool of glutathione, resulting in high ROS production and oxidative stress
  • DoxyR CSCs are between 4- to 10-fold more susceptible to the effects of Vitamin C
  • Doxycycline and Vitamin C may represent a new synthetic lethal drug combination for eradicating CSCs, by ultimately targeting both mitochondrial and glycolytic metabolism
  • inhibiting their propagation in the range of 100 to 250 µM
  • metabolic flexibility in cancer cells allows them to escape therapeutic eradication, leading to chemo- and radio-resistance
  • used doxycycline to pharmacologically induce metabolic inflexibility in CSCs, by chronically inhibiting mitochondrial biogenesis
  • This treatment resulted in a purely glycolytic population of surviving cancer cells
  • DoxyR cells are mainly glycolytic
  • MCF7 cells survive and develop Doxycycline-resistance, by adopting a purely glycolytic phenotype
  • Cancer stem cells (CSCs) are thought to be the “root cause” of tumor recurrence, distant metastasis and therapy-resistance
  • the conserved evolutionary similarities between aerobic bacteria and mitochondria, certain classes of antibiotics inhibit mitochondrial protein translation, as an off-target side-effect
  • Vitamin C was more potent than 2-DG; it inhibited DoxyR CSC propagation by > 90% at 250 µM and 100% at 500 µM
  • IC-50
  • DoxyR CSCs are between 4- to 10-fold more sensitive to Vitamin C than control MCF7 CSCs
  • Berberine, which is a naturally occurring antibiotic that also behaves as an OXPHOS inhibitor
  • treatment with Berberine effectively inhibited the propagation of the DoxyR CSCs by > 50% at 1 µM and > 80% at 10 µM.
  • 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
  • Doxycycline-driven aerobic glycolysis
  • new synthetic lethal strategy for eradicating CSCs, by employing i) Doxycycline (to target mitochondria) and ii) Vitamin C (to target glycolysis)
  • Doxycycline inhibits mitochondrial biogenesis and OXPHOS,
  • hibits glycolytic metabolism by targeting and inhibiting the enzyme GAPDH
  • CSCs act as the main promoter of tumor recurrence and patient relapse
  • 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
  • Vitamin C has been demonstrated to selectively kill cancer cells in vitro and to inhibit tumor growth in experimental mouse models
  • 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
  • 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
  • concurrent use of Vitamin C, with standard chemotherapy, reduces tumor recurrence and patient mortality
  • after oral administration, Vitamin C plasma levels reach concentrations of ~70-220 μM
  • intravenous administration results in 30- to 70- fold higher plasma concentrations of Vitamin C
  • 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
  • it has been shown that high-dose Vitamin C is more cytotoxic to cancer cells than to normal cells
  • 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
  • the concurrent use of Doxycycline and Vitamin C, in the context of this infectious disease, appeared to be highly synergistic in patients
  • 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
  • Doxycycline, an FDA-approved antibiotic, behaves as an inhibitor of mitochondrial protein translation
  • 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
  • Nathan Goodyear on 14 Jun 17
     
    Not especially new, but IV vitamin C + daily doxycycline found to kill cancer stem cells.
Nathan Goodyear

PO-238 Dichloroacetate (DCA) treatment affects mitochondrial activity and ste... - 0 views

esmoopen.bmj.com/...A113.1

cancer" DCA CSC pancreatic cancer stem cells cancer dichloracetic acid dichloroacetate

shared by Nathan Goodyear on 27 Nov 18 - No Cached
  • Nathan Goodyear on 27 Nov 18
     
    DCA shown to decrease tumor size in mouse model of pancreatic cancer stem cells.
Nathan Goodyear

Oncotarget | NADH autofluorescence, a new metabolic biomarker for cancer stem cells: Id... - 0 views

www.impactjournals.com/...index.php

vitamin C cancer alternative medicine natural

shared by Nathan Goodyear on 16 Mar 17 - No Cached
ngoclinh91 liked it
  • Nathan Goodyear on 16 Mar 17
     
    Vitamin C outperforms experimental drug in stopping cancer stem cell activity.
Nathan Goodyear

Aging | Doxycycline, Azithromycin and Vitamin C (DAV): A potent combination therapy for... - 0 views

www.aging-us.com/...text

cancer stem cells cancer azithromycin IV vitamin C vitamin C doxycycline CSC

shared by Nathan Goodyear on 21 May 19 - No Cached
  • Nathan Goodyear on 21 May 19
     
    Triple attack on cancer stem cells. Doxy and Azithromycin with vitamin C found to significantly inhibit CSC mitochondrial activity.
Nathan Goodyear

Molecular Targeting of H/MDM-2 Oncoprotein in Human Colon Cancer Cells and Stem-like Co... - 0 views

pubmed.ncbi.nlm.nih.gov/33419797

colon cancer peptides cancer CSC PNC-27 cancer stem cells PNC27

shared by Nathan Goodyear on 14 Aug 21 - No Cached
  • Nathan Goodyear on 14 Aug 21
     
    PNC-27 selectively kills colon cancer stem cells by binding to membrane H/MDM-2. This was an in vivo study. As with other studies, the result was tumor cell necrosis and associated high LDH release.
fitspresso

https://www.sightcare-co.com/ - 0 views

www.sightcare-co.com

sight care sightcare group training nearsightedness food for eyesight carey codd vitasight vision how to cure bad eye tips fix improve your red light eyes diet improvement skincare malaysia costos de medicare indonesia singapore eyecare

shared by fitspresso on 27 Sep 23 - No Cached
  • fitspresso on 27 Sep 23
     
    Sight Care | Official Site sightcare-co.com · by Sight Care Sight Care Only $49/Bottle Limited Time Offer! Sight Care Special Deal + Special 67% Discount Save $600 + 180 Days Money Back Guarantee #1.The Sight Care vision supplement is a dietary supplement for helping you improve your vision and brain health. Sight Care eye supplements are formulated to provide a synergistic blend of vitamins, minerals, antioxidants, and other bioactive compounds that are essential for maintaining healthy vision Regular Price: 147/per bottle Only for: $49/per bottle What Is Sight Care? This powerful vision support supplement is made with a unique blend of natural ingredients and plant extracts that work together synergistically to deliver numerous benefits for your brain and eye health. With Sight Care, you can expect to experience increased energy levels, improved eyesight, and an overall revitalized sense of well-being. Taking care of your vision health is not just about seeing clearly; it's also about maintaining your overall brain health. As we age, our vision deteriorates, and our eyes and brain can experience a decline in function, but there are steps you can take to support your visual and cognitive health. Regular eye exams are crucial for detecting and treating vision problems early on, and making healthy choices such as eating a nutritious diet and exercising regularly can also help. However, with busy schedules, it can be difficult to find the time to devote to a healthy lifestyle. This is where the Sight Care supplement comes in. It's designed to support both vision and brain health with its blend of natural ingredients that have been shown to promote healthy vision and cognitive function You must not compromise your eye health for momentary exhilaration. If you are glued to digital screens day and night, you must take measures to prevent eye diseases like age-related macular degeneration. The SightCare vision supplement has been made using 100% natura
Nathan Goodyear

Bisphenol A Promotes Human Prostate Stem-Proge... [Endocrinology. 2014] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...24424067

BPA bisphenol A Bisphenol-A prostate cancer xenoestrogen xenoestrogens

shared by Nathan Goodyear on 17 Jan 14 - No Cached
  • Nathan Goodyear on 17 Jan 14
     
    Another strike against BPA.  This time, BPA exposure during development increased hormone-dependent cancer risk in the prostate through its interaction with prostate stem-progenitor cells.  Again, we are being altered prior to birth.
Nathan Goodyear

Targeting colorectal cancer stem cells using curcumin and curcumin analogues: insights ... - 0 views

cancerci.biomedcentral.com/...s12935-015-0241-x

curcumin tumeric cancer colorectal cancer colon cancer

shared by Nathan Goodyear on 11 Sep 17 - No Cached
  • Nathan Goodyear on 11 Sep 17
     
    curcumin effective in inhibition of cancer and cancer stem cell activity through increasing apoptotic genes, affecting cellular signaling, altering growth factor receptors, microRNAs, tumor spheroid formation, and epithelial-mesenchymal transition; and found to be helpful in increasing chemo sensitivity to chemo and radiotherapy.
Nathan Goodyear

Ascorbate regulates haematopoietic stem cell function and leukaemogenesis : Nature : Na... - 0 views

www.nature.com/...nature23876.html

leukemia cancer vitamin c IV vitamin c Tet2

shared by Nathan Goodyear on 23 Oct 17 - No Cached
  • Nathan Goodyear on 23 Oct 17
     
    Low vitamin C levels accelerate the initiation of leukemia. High dose vitamin C found to accumulate and promote Tet2 activity in haematopoietic stem cells, thereby  decreasing initiation and progression of leukemia.
Nathan Goodyear

NADH autofluorescence, a new metabolic biomarker for cancer stem cells: Identification ... - 0 views

www.oncotarget.com/...text

propolis vitamin C CSC cancer stem cells

shared by Nathan Goodyear on 27 Apr 21 - No Cached
  • Nathan Goodyear on 27 Apr 21
     
    Vitamin C effective agains CSC.
Nathan Goodyear

Radiation‐Induced Reprogramming of Breast Cancer Cells - Lagadec - 2012 - STE... - 0 views

stemcellsjournals.onlinelibrary.wiley.com/...stem.1058

CSC cancer radiation cancer stem cells

shared by Nathan Goodyear on 07 May 21 - No Cached
  • Nathan Goodyear on 07 May 21
     
    ionizing radiation increased the number of BCSCs in the overall breast cancer cell population
Nathan Goodyear

Very small embryonic-like stem cells are involved in pancreatic regeneration and their ... - 0 views

stemcellres.biomedcentral.com/...s13287-015-0084-3

cancer stem cells VSEL

shared by Nathan Goodyear on 07 Jan 24 - No Cached
  • Nathan Goodyear on 07 Jan 24
     
    Dysfunctional VSEL triggers cancer? That is the proposal here.
Nathan Goodyear

UCLA's Jonsson Comprehensive Cancer Center : In the News : Radiation Treatments Generat... - 0 views

www.cancer.ucla.edu/index.aspx

radiation therapy treatment chemotherapy UCLA breast cancer stem cells

shared by Nathan Goodyear on 20 Mar 12 - No Cached
  • Nathan Goodyear on 20 Mar 12
     
    radiation therapy creates more aggressive cancer cells that are resistant to chemotherapy.  This study was done at UCLA on breast cancer cells.
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