Melanoma Defined By Increased Fatty Acid Synthesis And Unsaturation

haidut

Member
Joined
Mar 18, 2013
Messages
17,320
Location
USA / Europe
Yet another study implicating dysregulated fatty acid, instead of glucose, metabolism in cancer cells. Namely, the expression and activity of the enzyme fatty acid synthase (FASN) is increased in melanoma cells. Another interesting finding of the study is the increased unsaturation of the accumulated fats inside the tumor. The FASN enzyme synthesizes palmitic acid (PA) from glucose and this has been used by some critics of Peat to argue that saturated fats (SFA) such as PA drive cancer progression. Yet, the study below shows that as soon as PA is synthesized, it is quickly desaturate to the MUFA palmitoleic acid and, if there is stearic acid (SA) in the organism, the overexpressed desturase enzymes in the tumor quickly "degrade" SA to the MUFA oleic acid. It is the accumulation of those MUFA in lipid droplets that provide a "reservoir" of sorts that supplies the tumor with lipids for growth. SFA by themselves were actually inhibitory for tumor growth. In fact, the study found that if SFA levels increase and the SFA-to-unsaturated ratio reaches a specific level the tumor cells immediately undergo apoptosis. Thus, SFA is therapeutic because it increases differentiation and restrains tumor growth, and the tumor does everything it can to lower levels of SFA through desaturation as a way of preventing its own apoptosis. Administering either a FSAN inhibitor or a delta-9 desaturase enzyme inhibitor immediately triggered apoptosis in the melanoma cells. For those interested in FASN inhibitors - aspirin is one of the more better-known ones that is widely available, cheap, and OTC. However, medicine really hates aspirin and prefers using synthetic FASN such as orlistat or cerulenin.

https://authors.library.caltech.edu/105516/1/s41467-020-18376-x.pdf

"...Elevated FASN activities in the more differentiated melanoma cell lines suggest that the FASN pathway may constitute a metabolic susceptibility in just those phenotypes. In fact, interruption of this pathway has been previously studied for cancer drug development46. We tested this hypothesis by treating the cells with FASN inhibitors, 10 μM cerulenin46 or 0.2 μM TVB-316647, for 3 days. As hypothesized, the three most differentiated phenotypes exhibited the highest sensitivity to cerulenin and TVB-3166 while the two most undifferentiated cell lines are barely affected by such drug treatments (Fig. 2h and Supplementary Fig. 6d). These data demonstrate that single-cell Raman spectro-microscopy, integrated with transcriptional profiling, can uncover phenotype-specific druggable susceptibilities in cancer cells."

"...Indeed, bulk lipidomics data for M381 cells clearly shows that while droplet-enriched species of TAG and CE have the highest unsaturated fatty acid (UFA) composition among major lipid species (Fig. 3i), they only account for a small portion (in total <6%) of all major lipid species (Fig. 3j). Thus, M381 has elevated lipid unsaturation levels specifically within intracellular LDs."

"...To this end, we utilized a comparative analysis of Raman spectro-imaging on intracellular LDs to identify that lipid-unsaturation associated metabolic activities were uniquely upregulated in the mesenchymal M381 phenotype, as depicted in Fig. 7. "

https://www.caltech.edu/about/news/cancers-hidden-vulnerabilities

"...Wei says the team uncovered a few new metabolic susceptibilities in cancer cells, including fatty acid synthesis and mono-unsaturation, but adds that right now, the primary purpose of the research is to do fundamental science."
 
Similar threads
Thread starter Title Forum Replies Date
haidut Anti-histamines May Prevent, Treat Melanoma Scientific Studies 3
haidut Vitamin D May Stop Melanoma Growth Scientific Studies 0
debored13 Thymosin Alpha1-Fc Modulates The Immune System And Down-regulates The Progression Of Melanoma And Br Scientific Studies 1
ecstatichamster Another Fat Paradox - Fat Men More Likely To Survive “therapy” For Metastatic Melanoma Scientific Studies 4
haidut PUFA/Statins Promote UV Damage & Skin Cancer (melanoma), Cholesterol Is Protective Scientific Studies 4
haidut Aspirin May Help Treat Melanoma Scientific Studies 1
raypeatclips Cutaneous Malignant Melanoma Incidences Analyzed Worldwide UVB, Vitamin D Scientific Studies 3
A Safest Way To Go About Tanning Beds?-Melanoma In Family Ask For Help or Advice 13
Mito Daily Aspirin Linked To Double Melanoma Risk In Men Cancer 24
haidut Melanoma Is An Endocrine Tumor Like Breast Cancer - Driven By Estrogen Scientific Studies 13
G Preventing / Reversing Skin Cancer & Melanoma Skin 3
D Citrus Fruit Causes Sunburn And Increased Melanoma Risk? Diet 9
haidut Niacinamide May Prevent Melanoma Scientific Studies 4
Q DLPA & L-Tyrosine In Regards To Skin Cancer/melanoma Amino Acids 4
haidut Pregnenolone For Protection Against Melanoma Scientific Studies 4
P Pentoxifylline Inhibits Melanoma Tumor Growth And Angiogenesis By Targeting STAT3 Signaling Pathway Scientific Studies 0
haidut Fish oil consumption increases melanoma risk Scientific Studies 0
haidut NAC (cysteine) Increases Melanoma Spread Scientific Studies 58
S Citrus Consumption and Risk of Cutaneous Malignant Melanoma Scientific Studies 5
haidut Viagra May Be Linked To Melanoma Scientific Studies 7
haidut Melanoma Needs Glutamine To Grow And Dies Without It Cancer, Degenerative Diseases 15
haidut Coffee (caffeine) protects against melanoma Scientific Studies 6
charlie Aspirin Vs. Melanoma: Study Suggests Headache Pill Cancer 2
C Why do indigenous people have bigger and more defined jaws? Diet 1
bzmazu "Terrorist" Now Defined As Anyone Disagreeing with Establishment Dogma Breaking News 28
GreekDemiGod Peaty supplements / diet increased my Prolactin and Estradiol. Why? Ask For Help or Advice 24
GorillaHead Increased salt intake leads to endothelial dysfunction? Diet 1
haidut Reduced pyruvate and/or increased lactate drive heart failure Scientific Studies 0
Vileplume NDT Causing Increased Heart Rate, but Not Helping Temps Throughout the Day--What's Going on? Natural Dessicated Thyroid 30
M aspirin and increased hair loss Hair & Nails 4
J Increased Nipple Hair In Men Male Issues 3
Giraffe Increased Mortality After The Introduction Of Diphtheria–Tetanus–Pertussis Vaccine Vaccines 5
Lewis Acid Lucid Dreaming: Increased Connectivity Between Frontopolar Cortex & Temporoparietal Areas Mind, Sleep, Stress 3
Harryedgar Fat Loss, PUFA, Estrogen Detox And Increased Metabolism Weight 0
Drareg Obesity And COVID 19 Increased Risk Of Adverse Outcomes Scientific Studies 5
J Increased Breathing After Aspirn & Small Meal Metabolism 4
Tristan Loscha Calcitriol+VDR:Increased Activity Of P-Glycoprotein=Decrease Of HAβ42 Plaque D 0
haidut Pulmonary Hypertension (usually Fatal) Driven By Increased Fat Oxidation (FAO) Scientific Studies 0
tankasnowgod The Health Cost Of Lockdowns- Death Tolls From Increased Suicide, Blood Shortages, And Other Effects Viruses, Parasites, Fungus, Vaccines 493
md_a High Levels Of Iron In The Lung Linked To Increased Asthma Severity Scientific Studies 0
Mito Serum Progesterone Levels Increase Linearly With Increased Dosage Progesterone 1
GorillaHead Can Increased Insulin Sensitivity Make You Hungry? Blood Sugar 1
K Copper Supplementation Increased Brown Spots Number Minerals 56
S Peating Increased Attractiveness, And Getting Too Much Attention Ask For Help or Advice 8
Inaut How To Restore Liver Glycogen For Increased Metabolism Metabolism 9
B Anti-Peat Lean Mass Increased 3x As Much With PUFA Versus SFA Debate - Anti-Peat 21
A Cyproheptadine Increased My Cold Sensitivity Even More Ask For Help or Advice 4
haidut Increased Fatty Acid Synthesis (FAS) Is Simply A Sign Of Oxygen Deficiency / Low Metabolism Scientific Studies 1
L Increased Blood Pressure And Pulse Rate With Bag Breathing? CO2, Bag Breathing 9
Blossom Antibiotics And Increased Risk For Parkinson's Disease? Articles & Scientific Studies 9

Similar threads

Top