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Nathan Goodyear

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

shared by Nathan Goodyear on 08 Dec 17 - No Cached
  • Vitamin C was ~10 times more potent than 2-DG for the targeting of CSCs
  • Cancer stem-like cells (CSCs) are thought to be the root cause of chemotherapy-resistance and radio-resistance
  • 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
  • ...26 more annotations...
  • mitochondrial biogenesis may be a key driver of the CSC phenotype
  • Our results indicate that increased mitochondrial oxidative stress and high NADH levels are both key characteristics of the CSC metabolic phenotype
  • 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
  • CSCs may be strictly dependent on NAD(P)H to maintain their enhanced mitochondrial function
  • 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.
  • Since glycolysis is especially critical for maintaining the TCA cycle, OXPHOS and overall mitochondrial function, we next assessed the effects of known glycolytic inhibitors
  • 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
  • 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
  • caffeic acid phenyl ester (CAPE), a key component of honey-bee propolis, has potent anti-cancer properties
  • Propolis has a strong history of medicinal use, dating back more than 2,000 years
  • Because of it aromatic ring structure (Figure 8), we speculated that CAPE might function as a potent inhibitor of oxidative mitochondrial metabolism
  • CAPE quantitatively inhibits the mitochondrial oxygen consumption rate (OCR) and, in turn, induces the onset of aerobic glycolysis (ECAR)
  • CAPE shows a clear selectivity for targeting CSCs and adherent cancer cells, relative to normal fibroblasts.
  • CAPE functions as a “natural” mitochondrial OXPHOS inhibitor, that preferentially targets the CSC sub-population. This could explain CAPE’s known anti-cancer properties
  • 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
  • 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.
  • high NADH is a property that is conserved between normal and cancerous stem cells
  • 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
  • CSCs may be strictly dependent on NADH to maintain their enhanced mitochondrial function
  • 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
  • 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.
  • 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
  • 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
  • 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
  • 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
  • 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.
  • Nathan Goodyear on 08 Dec 17
     
    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.
Nathan Goodyear

Phosphodiesterase 5 Inhibitors Enhance Chemotherapy Killing in Gastrointestinal/Genitou... - 0 views

www.ncbi.nlm.nih.gov/...PMC3935155

chemotherapy phosphodiesterase 5 inhibitors repurposed drugs PDE inhibitors PDE5I phosphodiesterase inhibitors cancer PDE5 inhibitors

shared by Nathan Goodyear on 08 Mar 21 - No Cached
  • Nathan Goodyear on 08 Mar 21
     
    PDE inhibitors repurposed to augment chemotherapy in treatment of cancer.
Nathan Goodyear

Phosphodiesterase-5 inhibitors in the management of cancer - 0 views

cAMP PDE5 inhibitors phosphodiesterase inhibitors PDE chemotherapy phosphodiesterase 5 inhibitors cancer cyclic AMP

shared by Nathan Goodyear on 16 Feb 21 - No Cached
  • Nathan Goodyear on 16 Feb 21
     
    Phosphodiesterase 5 inhibitors shown to have numerous effects against cancer, including restoring treatment sensitivity to chemotherapy.
Nathan Goodyear

Inhibition of breast cancer cell migration by activation of cAMP signaling - PubMed - 0 views

pubmed.ncbi.nlm.nih.gov/26022351

phosphodiesterase inhibitors breast cancer phosphodiesterase 5 inhibitors cyclic AMP PDE5 inhibitors cAMP

shared by Nathan Goodyear on 08 Mar 21 - No Cached
  • Nathan Goodyear on 08 Mar 21
     
    Increase in cAMP found to inhibit breast cancer motility and migration. Here, they used cAMP analogs, forskolin and PDE inhibitors.
Nathan Goodyear

Potent Inhibition of Human Phosphodiesterase-5 by Icariin Derivatives - Journal of Natu... - 0 views

pubs.acs.org/...np800049y

phosphodiesterase 5 inhibitors ED Icariin natural horny goat weed PDE5 phosphodiesterase inhibitors

shared by Nathan Goodyear on 12 Jun 13 - No Cached
  • Nathan Goodyear on 12 Jun 13
     
    A natural phosphodiesterase 5 inhibitor would be nice.  This study looked at a lot of traditional herbal remedies to block phosphodiesterase 5 activity.  Only Epimedii herb with the active ingredient icariin worked.  Other preparations were shown to work, but via different mechanisms.  This is a review of studies looking at these herbal preparations.
Nathan Goodyear

International Journal of Impotence Research - PDE5 inhibitors beyond erectile dysfunction - 0 views

www.nature.com/...3901577a.html

ED phosphodiesterase 5 inhibitors impotence PDE5

shared by Nathan Goodyear on 12 Jun 13 - No Cached
  • Nathan Goodyear on 12 Jun 13
     
    Good review on phosphodiesterase 5 inhibitors.
Nathan Goodyear

RB&E | Full text | Aromatase inhibitors in men: effects and therapeutic options - 0 views

www.rbej.com/93

aromatase inhibitors men male hormone hormones

shared by Nathan Goodyear on 11 Jun 13 - No Cached
  • Nathan Goodyear on 11 Jun 13
     
    Great review on aromatase inhibitors in men.
Nathan Goodyear

Natural Products as Aromatase Inhibitors - 0 views

www.ncbi.nlm.nih.gov/...PMC3074486

natural aromatase inhibitors products inhibition

shared by Nathan Goodyear on 18 Dec 12 - No Cached
  • Nathan Goodyear on 18 Dec 12
     
    natural aromatase inhibitors.
Nathan Goodyear

The role of 5-alpha reductase inhibitors in prostate pathophysiology: Is there an addit... - 1 views

www.ncbi.nlm.nih.gov/...PMC2698784

prostate 5 alpha reductase 5 alpha reductase inhibitors hormones male men male hormones

shared by Nathan Goodyear on 01 Jul 16 - No Cached
  • Nathan Goodyear on 01 Jul 16
     
    good review of 5-alpha reductase inhibitor and prostate pathophysiology.  Type I is increased in prostate cancer.  
Nathan Goodyear

The role of androgens and estrogens in the pathogenes... [J Urol. 1988] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...3172358

prostatitis E2 estradiol testosterone T:E2 testosterone:Estradiol aromatase inhibitors

shared by Nathan Goodyear on 01 May 12 - No Cached
  • Testosterone can block the effect of estradiol on prostatitis, however treatment with an anti-estrogen or an aromatase inhibitor to block estrogen action does not improve prostatitis in the rat
  • Nathan Goodyear on 01 May 12
     
    Estradiol and imbalanced Testosterone:Estradiol ratio contributes to prostatitis.  In this study, with rats, aromatase inhibitors did not improve prostatitis.
Nathan Goodyear

International Journal of Impotence Research - Treatment of testosterone-induced gynecom... - 0 views

www.nature.com/...3901154a.html

arimidex anastrozole low T testosterone aromatase activity inhibition inhibitor impotence ED

shared by Nathan Goodyear on 26 Feb 12 - No Cached
  • Nathan Goodyear on 26 Feb 12
     
    arimidex, also known as anastrozole, is shown to be an effective aromatase inhibitor in men.  These case studies used arimidex to successfully stimulate testosterone production by limiting testosterone to estrogen production.  This was found to be useful in the treatment of gynecomastia.
Nathan Goodyear

Aromatase inhibitors for male infertility. [J Urol. 2002] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...11792932

male infertility anastrozole arimidex aromatase inhibitor inhibition Testosterone:estradiol

shared by Nathan Goodyear on 26 Feb 12 - No Cached
  • Nathan Goodyear on 26 Feb 12
     
    aromatase inhibitor, arimidex (anastrozole), shown to be effective therapy in male infertility in those with high aromatase activity.  The effect was seen through improved Testosterone:Estradiol ratio through aromatase inhibition.
Nathan Goodyear

The androgen metabolite 5alpha-androstane-3beta,17beta-diol (3betaAdiol) induces breast... - 0 views

www.researchgate.net/...aromatase_inhibitor_resistance

breast cancer aromatase aromatase inhibitors estradiol estrogen 3-beta androstanediol Testosterone DHT 3 beta HSD receptor receptors ER alpha ER-alpha ER beta ER-beta hormone hormones women

shared by Nathan Goodyear on 21 Jan 14 - No Cached
  • Nathan Goodyear on 21 Jan 14
     
    Great article!!  Nice discussion of the complexity of hormones.  Women on aromatase inhibitors can make estrogen from Testosterone.  This is important with estrogen sensitive cancer as in breast cancer.  This will occur via alternative pathways: Testosterone to DHT via 5 alpha reductase and then DHT to 3 beta androstanediol via 3 beta HSD.  3 beta androstanediol is a male hormone metabolite that binds to estrogen receptors.  The affinity is less than Estradiol, but appears to have a higher affinity for ER beta over ER alpha. 
Nathan Goodyear

The what, why and how of aromatase inhibitors: hormonal agents for treatment and preven... - 0 views

www.ncbi.nlm.nih.gov/...PMC2228389

breast cancer aromatase inhibitors aromatase hormones

shared by Nathan Goodyear on 08 Sep 15 - No Cached
  • Nathan Goodyear on 08 Sep 15
     
    aromatase inhibitors and breast cancer.
Nathan Goodyear

Pharmacological approaches to reducing the risk of... [Eur Urol. 2009] - PubMed result - 0 views

www.ncbi.nlm.nih.gov/...19200641

finasteride 5 alpha-reductase inhibitors prostate cancer

shared by Nathan Goodyear on 02 Mar 11 - No Cached
  • 5alpha-reductase inhibitors (5-ARIs).
  • there is no evidence that 5-ARIs or any other approach to prostate cancer risk reduction will reduce the risk of lethal prostate cancers
  • Nathan Goodyear on 02 Mar 11
     
    5 alpha-reductase inhibitors, such as finasteride, have not been shown to reduce lethal prostate cancer
Nathan Goodyear

Induction and Inhibition of Aromatase (CYP19) Activity by Natural and Synthetic Flavono... - 0 views

toxsci.oxfordjournals.org/...70.full

isoflavones quercetine aromatase inhibitor inhibition

shared by Nathan Goodyear on 28 Sep 11 - No Cached
  • Natural flavones were consistently more potent inhibitors
  • The natural flavone quercetin and isoflavone genistein induced aromatase activity 4- and 2.5-fold induction
  • Nathan Goodyear on 28 Sep 11
     
    Quercetin shown to be a good natural aromatase inhibitor
Nathan Goodyear

ScienceDirect - The Journal of Urology : AROMATASE INHIBITORS FOR MALE INFERTILITY - 0 views

www.sciencedirect.com/...S0022534701690992

AROMATASE INHIBITORS MALE INFERTILITY Testosterone Estradiol hormone hormonal imbalance

shared by Nathan Goodyear on 10 Oct 11 - No Cached
  • Nathan Goodyear on 10 Oct 11
     
    aromatase inhibition in men to increase Testosterone:Estradiol ratio.  Men with infertility have a low Testosterone:Estradiol ratio.  Aromatase inhibitors inhibit Testosterone to Estradiol conversion
Nathan Goodyear

Effect of hop (Humulus lupulus L.) flavono... [J Agric Food Chem. 2006] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...16608212

Hops aromatase inhibitor aromatase inhibition aromatase inhibitors estrogen men male hormone hormones aromatase Humulus Lupulus

shared by Nathan Goodyear on 20 May 14 - No Cached
  • Nathan Goodyear on 20 May 14
     
    Hops is a natural aromatase inhibitor
Nathan Goodyear

Use of 5α-reductase inhibitors for lower urinary tract symptoms and risk of p... - 0 views

www.bmj.com/bmj.f3406

5 alpha reductase 5 alpha reductase inhibitors prostate cancer LUTS men male hormone hormones

shared by Nathan Goodyear on 09 Feb 15 - No Cached
  • Nathan Goodyear on 09 Feb 15
     
    5alpha reductase inhibitors associated with decreased risk of Gleason 2-7 prostate cancer in men with LUTS and enlarged prostate.
Nathan Goodyear

Prostate Biopsy in Response to a Change in Nadir Prostate Specific Antigen of... - 0 views

www.jurology.com/...abstract

5 alpha reductase 5 alpha reductase inhibitors PSA prostate cancer men male hormone hormones

shared by Nathan Goodyear on 09 Feb 15 - No Cached
  • Nathan Goodyear on 09 Feb 15
     
    5 alpha reductase inhibitor therapy reduces PSA and prostate volume.  The level of change may be used to aid in prostate cancer diagnosis.  Those with eventual diagnosis had Gleason 7 or higher.
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