Fatty Acid Oxidation (FAO) Inhibition Abrogates Triple-negative Breast Cancer

haidut

Member
Joined
Mar 18, 2013
Messages
17,533
Location
USA / Europe
The evidence for the role of excessive FAO in cancer keeps piling on. As many of my readers know, triple-negative breast cancer is one of the most difficult to treat and its proportion of total breast cancer cases has been steadily rising over the last 20 years. When a patient is diagnosed with such a cancer, oncologists waste no time and put the patient on an aggressive regimen of radiation and cytotoxic chemotherapy as they think this is the patient's only chance of surviving it. Unlike the more common hormone-sensitive cancers, oncologists do not believe this type of cancer can be slowed down or controlled to the point where the patient lives with it as a form of chronic disease without it becoming life-threatening. Needless to say, metabolic therapies are not even mentioned to the patient simply because oncology does not believe such therapies stand any chance at treating the cancer. Well, the study below begs to disagree. It not only highlights yet again the crucial role of FAO in cancer initiation/progression but it also demonstrates that simply inhibiting FAO can fully stop the cancer growth and ensure 100% survival (see Fig. 4e/4f below). The FAO drug used in the study was etomoxir and it is a so-called CPT1 inhibitor. The HED of etomoxir that abrogated the cancer was about 5mg/kg daily. Unfortunately, etomoxir is severely hepatotoxic and as such its clinical use has been halted, so it would be next to impossible to obtains it for human use or convince a doctor to prescribe it. Fortunately, niacinamide is also a CPT1 inhibitor and can achieve the same effects as etomoxir with a human dose of about 7mg/kg. Needless to say, other FAO inhibitors like aspirin, Mildronate/Meldonium, ethyl pyruvate + ethyl acetoacetate, progesterone, etc can also be used as interventions and will likely be highly synergistic with niacinamide.

Inhibition of fatty acid oxidation as a therapy for MYC-overexpressing triple-negative breast cancer. - PubMed - NCBI
"...The observed reduction in bioenergetic metabolism prompted us to analyze the effects of prolonged FAO inhibition on the growth of MO-TNBC tumors. We performed orthotopic transfer of MTB-TOM or HCI-002 PDX tumors into the mammary fat pad of FVB/N or NOD/SCID mice, respectively. We administered 40 mg/kg etomoxir or vehicle by IP injection daily for 14 d to MTB-TOM allograft-bearing mice. We administered 40 or 60 mg/kg etomoxir or vehicle by IP injection daily for 21 d to HCI-002 PDX-bearing mice. Etomoxir treatment resulted in significant attenuation of tumor growth in both models, and a significant extension of the time to ethical endpoint in the PDX model (Fig. 4d,e). In contrast, we observed no significant attenuation in tumor growth of the HCI-009 MYClow TNBC PDX tumors treated with 40 mg/kg etomoxir (Fig. 4a,f).

"...Although etomoxir treatment of cultured MO-TNBC cell lines had a marked effect on cell proliferation without appreciable changes in cell death (Supplementary Fig. 3), in vivo FAO inhibition resulted in a concurrent decrease in proliferation and an increase in apoptosis of MO-TNBC (Fig. 4g). These results are consistent with FAO playing a more critical role for in vivo tumor development. Elevated MYC expression was recently discovered to be a defining factor of TNBC1,2. The present study is amongst the first to investigate the role of MYC in TNBC metabolism in vivo. Here we show that MO-TNBC upregulates FAO, that TNBC is sensitive to FAO inhibition in a MYC-dependent manner, and that FAO inhibition abrogates growth of distinct models of MO-TNBC in vitro and in vivo. This work supports a critical role for FAO in TNBC7,8, and identifies a dependency on MYC as a marker for this phenotype. Inhibition of FAO demands further investigation as a therapeutic strategy for MO-TNBC."

fao_breast_cancer.png
 

charlie

The Law & Order Admin
Joined
Jan 4, 2012
Messages
11,756
Location
USA
Amazing! Would love to try out Mildronate. In the meantime the wonder drug Aspirin will do.
 
Joined
Aug 21, 2018
Messages
1,122
Etomoxir seems to be 4-chlorophenol derivate, highly speculative but yet I say it's a mitochondrial uncoupler like other chlorophenols, probably.
 
Similar threads
Thread starter Title Forum Replies Date
Highserotonin90 Inhibit / slow down excessive Fatty acid oxidation (FAO). Experiments 19
Lokzo Glycine Reduces NAFLD by modulating fatty acid oxidation, glutathione synthesis, and the gut microbiome - 2020 Supplements, Pharmaceutical Drugs 21
Hans The Dope On Blocking Fatty Acid Oxidation Articles & Scientific Studies 83
S-VV Fructose Decreases Hepatic Fatty Acid Oxidation Scientific Studies 1
Hans Methylene Blue Inhibits Fatty Acid Oxidation And Improve Metabolic Flexibility In The Heart Supplements, Pharmaceutical Drugs 0
haidut Sterilizing The Gut Restores Insulin Sensitivity By Reducing Fatty Acid Oxidation Scientific Studies 69
Broken man Is Oregano Oil Fatty Acid Oxidation Inhibitor? Study Inside Supplements, Pharmaceutical Drugs 20
haidut Fatty Acid Oxidation (FAO) Makes Cancer Therapy-resistant, Niacinamide May Help Scientific Studies 0
L Does Riboflavin Stop Fatty Acid Oxidation? Supplements, Pharmaceutical Drugs 1
haidut Palmitic Acid (palmitate) Is A Fatty Acid Oxidation Inhibitor More Powerful Than Mildronate Scientific Studies 30
tyw Fatty Acid Oxidation Is Required For The Respiration And Proliferation Of Malignant Glioma Cells Scientific Studies 2
haidut Why glucose oxidation is preferable to fatty acid oxidation Scientific Studies 11
haidut Hypoglycin - A Powerful Fatty Acid Oxidation Inhibitor Scientific Studies 10
haidut Niacinamide Lowers Fatty Acid Oxidation By Inhibiting SIRT1 Scientific Studies 20
I 2008 Study ; Comparison of lipid and fatty acid profiles of commercially raised pigs with laboratory pigs and wild-ranging warthogs Scientific Studies 0
haidut Melanoma Defined By Increased Fatty Acid Synthesis And Unsaturation Scientific Studies 0
shine Question Regarding Fatty Acid Profile Of Low Fat Milk Milk 7
Jake sullivan Fatty Acid Composition Of Young Adults Analysis Polyunsaturated Fats, Seed Oils 8
G "Can Essential Fatty Acid Deficiency Predispose To AIDS?" Polyunsaturated Fats, Seed Oils 36
L Erucic Acid: The Omega-9 Fatty Acid Bad Enough To Scare Even Vegetable Oil Growers? Diet 1
haidut Increased Fatty Acid Synthesis (FAS) Is Simply A Sign Of Oxygen Deficiency / Low Metabolism Scientific Studies 2
O TRT In Saturated Fatty Acid Esters Male Issues 5
haidut Inhibiting Fatty Acid Synthesis (FAS) Dramatically Improves Sepsis Survival Rate Scientific Studies 5
haidut Mitochondrial Damage And Fatty Acid Buildup, Not Glucose, May Drive Diabetes Scientific Studies 11
GutFeeling The Development Of Essential Fatty Acid Deficiency In Healthy Men Fed Fat-free Diets Scientific Studies 2
Mito Omega-3 Fatty Acid Supplements Do Not Prevent Cancer Or CVD Articles & Scientific Studies 0
haidut A Saturated Fatty Acid (caprylic) Can Obliterate Tumors (in-vivo) In Just Hours Scientific Studies 53
K Preventing Fatty Acid Release Weight 14
haidut Transdermal Delivery Of Saturated Fat Changes Systemic Fatty Acid Profile Scientific Studies 41
pimpnamedraypeat Why Is "polyunsaturated Fatty Acid" A Popular Search Term In Poland? Ask For Help or Advice 2
D Effects Of Exercise On The Fatty-acid Composition Of Blood And Tissue Lipids Scientific Studies 1
P Inflammation Mediates Free Fatty Acid-induced Insulin Resistance Articles & Scientific Studies 0
P Saturated Fatty Acids,including Lauric Acid Activates TLR4 Articles & Scientific Studies 5
Makrosky Targeting Metastasis-initiating Cells Through The Fatty Acid Receptor CD36 Scientific Studies 2
A Alpha-Linolenic Acid: An Omega-3 Fatty Acid With Neuroprotective Properties Articles & Scientific Studies 11
Travis Fatty Acid Saturation And Longevity Fats 13
Koveras Sexually Dimorphic Brain Fatty Acid Composition In Low And High Fat Diet-fed Mice Scientific Studies 0
P Prolonged Niacin Treatment Leads To Increased Adipose Tissue Polyunsaturated Fatty Acid Synthesis Scientific Studies 5
Pointless The Effect Of B12 Deprivation On The Enzymes Of Fatty Acid Synthesis Scientific Studies 0
sctb Altering Fatty Acid Availability Does Not Impair Running To Fatigue Articles & Scientific Studies 1
P Adipose tissue metabolism in essential fatty acid deficienty. Effects of prostaglandin e1, epinephri Articles & Scientific Studies 0
P The Effects Of Essential Fatty Acid Deficiency On Brown Adipose Tissue Activity In Rats Maintained A Articles & Scientific Studies 1
haidut The Fatty Acid Syndrome (Randle Cycle) Scientific Studies 30
Hugh Johnson Polyunsaturated fatty acid deficiency reverses effects of alcohol on mitochondrial energy metabolism Scientific Studies 0
Hugh Johnson Omega-3 fatty acid deficiency during perinatal development increases serotonin turnover in the prefr Scientific Studies 0
Hugh Johnson Maternal Iron Deficiency Alters Essential Fatty Acid And Eicosanoid Metabolism And Increases Locomot Articles & Scientific Studies 4
haidut Elevated free fatty acid cause insulin resistance Scientific Studies 1
P Association of marine omega-3 fatty acid levels with telomeric aging in patients with coronary heart Articles & Scientific Studies 1
S A Reply To Ray Peat On Essential Fatty Acid Deficiency Polyunsaturated Fats, Seed Oils 58
B Inducing an essential fatty acid deficiency in an adult hu.. Miscellaneous Health Discussions 0

Similar threads

Top