CRM Cancer Research Results
CRM, Calorie restriction mimetics (CRMs): Click to Expand ⟱
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Calorie restriction mimetics (CRMs) are compounds that appear to mimic some of the biochemical effects of caloric restriction without the need to actually reduce caloric intake.
-Resveratrol:Known for activating sirtuins (e.g., SIRT1)
-Curcumin
-Quercetin
-EGCG
-Spermidine
-Fisetin
-Berberine
-Pterostilbene
-Hydroxytyrosol
-Sulforaphane
-Cinnamaldehyde
-Nicotinamide Riboside (NR) and Nicotinamide Mononucleotide (NMN)
-Alpha-Ketoglutarate (AKG)
-Rapamycin (Sirolimus
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Scientific Papers found: Click to Expand⟱
*CRM↑, Altogether, these findings identify aspirin as an evolutionary conserved CRM.
*HATs↓, inhibit the acetyltransferase activity of EP300
*NF-kB↓, aspirin reportedly inhibits the activation of the pro-inflammatory transcription factor nuclear factor kappa light-chain enhancer of activated B cell (NF-κB)
*EP300↓, Salicylate Inhibits EP300 Acetyltransferase by Competing with AcCoA
*antiOx↑, Baicalein supplementation in male Wistar rats significantly alleviated pro-oxidant markers and improved antioxidant profile.
*ROS∅, Baicalein has the potential to maintain extracellular reactive oxygen species levels and redox homeostasis during the aging process, an effect that is similar to CR.
*CRM↑, conclude that Baicalein has the potential to maintain extracellular reactive oxygen species levels and redox homeostasis during the aging process, an effect that is similar to CR.
*CRM↑, Chlorogenic acid (CGA) acts as a caloric restriction mimetic
*neuroP↑, CGA exerted neuroprotective effects against Aβ1-42-induced oxidative stress and impaired ion transporter and acetylcholinesterase activities, serving as a promising therapeutic candidate for neurodegenerative diseases, such as Alzheimer's disease.
*AChE↓,
*OS↑, The permanent or periodic reduction of calorie intake without malnutrition (caloric restriction and fasting) is the only strategy that reliably extends healthspan in mammals including non-human primates.
*AntiAge↑, CRMs will become part of the pharmacological armamentarium against aging and age-related cardiovascular, neurodegenerative, and malignant diseases.
*cardioP↑,
*neuroP↑,
AntiCan↑,
*TNF-α↓, In healthy humans, CR also decreases the levels of circulating tumor necrosis factor-α
*Weight↓, In obese humans, CR promotes significant weight loss and improves general health
*BP↓, Figure 1
*Inflam↓,
*Insulin↓,
*ROS↓,
*AMPK↑,
*mTOR↓,
*SIRT1↑, Resveratrol and Other SIRT1 Activators
CRM↑, Figure2: HCA, Resveratrol, Spermidine, Aspirin, Berberine, EGCG, QC, etc
CRM↑,
ChemoSen↑, CR mimetics as adjuvant therapies to enhance the efficacy of chemotherapy, radiation therapy, and novel immunotherapies.
RadioS↑,
eff↑, CR mimetics as adjuvant therapies to enhance the efficacy of chemotherapy, radiation therapy, and novel immunotherapies.
eff↑, Intermittent fasting has been shown to enhance treatment with both chemotherapy and radiation therapy.
IGF-1↓, Exposure to an energy restricted diet results in reduced systemic glucose and growth factors such as IGF-1
TumCG↓, reduction of IGF-1 levels in CR results in decreased tumor growth and progression
AMPK↑, CR also induces activation of AMP-activated protein kinase (AMPK), (working in opposition to IGF-1)
eff↑, Recent research in our lab showed that combining autophagy inhibition with a CR regimen reduced tumor growth more than either treatment alone [20].
ChemoSen↑, Short-term fasting has been shown to improve chemotherapeutic treatment with etoposide [40], mitoxantrone, oxaliplatin [41], cisplatin, cyclophosphamide, and doxorubicin [42] in transgenic and transplant mouse models
RadioS↑, Alternate day fasting has also been shown to improve the radiosensitivity of mammary tumors in mice
ROS↑, improve the radiosensitivity: likely due to enhanced oxidative stress and DNA damage during short-term fasting on cancer cells.
DNAdam↑,
eff↑, fasting-mimicking diet, in which mice are fed the same amount of food as control mice, albeit with a severely reduced caloric density, showed a similar reduction in tumor growth as short-term starvation
HO-1↓, fasting-mimicking diet were associated with increased autophagy in the cancer cells and reduced heme oxygenase-1 (HO-1) in the microenvironment
CRM↑, Hydroxycitric acid (HCA) is considered a bona fide CRM since it depletes acetyl-CoA pools by acting as a competitive inhibitor of ATP citrate lyase (ACLY), ultimately repressing protein acetylation and promoting autophagy.
ACLY↓, competitive inhibitor of ATP citrate lyase (ACLY)
TumAuto↑, promoting autophagy.
Inflam↓, reduce inflammation and tumour development
TumCG↓,
toxicity∅, HCA appear to have a low or negligible impact in terms of acute or chronic toxicity, genotoxicity, reproductive failure and teratogenicity
lipoGen↓, decreases lipogenesis, insulin resistance, inflammation and oxidative stress
*ROS↓, H2O2 treatment: Strikingly, the molecule was able to largely prevent the massive cell death (PI+ cells) caused by the intense oxidative stress. In parallel there was a sharp increase of live cells with high ROS levels
*OCR↓, chronic exposure to 5 mM HCA (from cell seeding) down-regulated yeast OCR
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*antiOx↑, Anti‐oxidative mechanism of lycopene
*ROS↓, Lycopene inhibits ROS generation and subsequent oxidative stress by inducing antioxidant enzymes (SOD, CAT, GSH, GSH‐Px, and GST) and limiting MDA level and lipid peroxidation (LPO).
*SOD↑,
*Catalase↑,
*GSH↑,
*GSTs↑,
*MDA↓,
*lipid-P↓,
*NRF2↑, Lycopene also prevents ROS release by upregulating Nrf2‐mediated HO‐1 levels and inhibiting iNOS‐activated NO generation
*HO-1↑,
*iNOS↓,
*NO↓,
*TAC↑, upregulating total antioxidant capacity (TAC) and direct inhibition of 8‐OHdG, NOX4.
*NOX4↓,
*Inflam↓, Anti‐inflammatory mechanism of lycopene.
*IL1↓, IL‐1, IL‐6, IL‐8, IL‐1β, and TNF‐α release.
*IL6↓,
*IL8↓,
*IL1β↓,
*TNF-α↓,
*TLR2↓, prevents inflammation by inhibiting toll‐like receptors TLR2 and TLR4 and endothelial adhesion molecules VCAM1 and ICAM‐1.
*TLR4↓,
*VCAM-1↓,
*ICAM-1↓,
*STAT3↓, inhibiting STAT3, NF‐κB, ERK pathway, and IL‐6 and TNF‐α release.
*NF-kB↓,
*ERK↓,
*BP↓, Another clinical study demonstrated that consumption of raw tomato (200 g/day) could prevent type 2 diabetes‐associated cardiovascular diseases by lowering systolic and diastolic blood pressure, upregulating ApoA1, and downregulating ApoB levels
ROS↓, lycopene suppresses the metastasis of the SK‐HEP‐1 cell line by NOX‐4 mRNA expression inhibition and the reactive ROS intracellular activity inhibition
PGE2↓, Lycopene is also used to treat colorectal cancer cells in humans, and the introduction of lycopene decreases the prostaglandin E2 and nitric oxide levels
cardioP↑, Lycopene‐rich foods can be highly beneficial in preventing cardiovascular diseases as lycopene is a potential source of antioxidants
*neuroP↑, beneficial role of lycopene on aging‐related neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease, has been confirmed in both experimental and clinical trials
*creat↓, Several pre‐clinical studies reported that lycopene treatment significantly reduced serum urea and serum creatinine, as well as reversed various toxic chemical‐induced nephrotoxicity and oxidative damage by exhibiting excellent antioxidative properti
*RenoP↑,
*CRM↑, its potency in treating aging disorders and its role as a mimic of caloric restriction.
*AntiDiabetic↑, Metformin is a drug commonly prescribed to treat patients with type 2 diabetes.
*AntiAge↑, Here we show that long-term treatment with metformin (0.1% w/w in diet) starting at middle age extends healthspan and lifespan in male mice
*toxicity⇅, while a higher dose (1% w/w) was toxic.
*CRM↑, The effects of metformin resembled to some extent the effects of caloric restriction, even though food intake was increased.
*Strength↑, Treatment with metformin mimics some of the benefits of calorie restriction, such as improved physical performance, increased insulin sensitivity, and reduced LDL and cholesterol levels without a decrease in caloric intake
*LDL↓,
*AMPK↑, metformin increases AMP-activated protein kinase activity and increases antioxidant protection, resulting in reductions in both oxidative damage accumulation and chronic inflammation
*TAC↑,
*ROS↓, consistent with decreased oxidative stress damage in the liver of metformin-treated mice
*Inflam↓, Metformin inhibits chronic inflammation
Risk↓, metformin treatment has been associated with reduced risk of cancer4 and cardiovascular disease
*cardioP↑,
*ALAT↓, Ala aminotransferase (U/L) 90 ± 58 64 ± 29
*NRF2↑, The increase in Nrf2/ARE reporter activity occurred with an ED50 of ~1.5 mM metformin without reduction in cell survival
*SOD2↑, 0.1% metformin contributed to an increase in the level of antioxidant and stress response proteins, including SOD2, TrxR1, NQO1 and NQO2
*TrxR1↑,
*NQO1↑,
*NQO2↑,
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*AntiDiabetic↑, Metformin has been designated as one of the most crucial first-line therapeutic agents in the management of type 2 diabetes mellitus.
*AMPK↑, acts majorly by activating AMPK (Adenosine Monophosphate-Activated Protein Kinase) in the cells and reducing glucose output from the liver.
*glyC↓, It also decreases advanced glycation end products and reactive oxygen species production in the endothelium apart from regulating the glucose and lipid metabolism
*ROS↓,
*cardioP↑, hence minimizing the cardiovascular risks.
*neuroP↑, Preclinical studies have also shown some evidence of metformin’s neuroprotective role in Parkinson’s disease, Alzheimer’s disease, multiple sclerosis and Huntington’s disease.
*Half-Life↝, The plasma half-life of metformin is 2–3 hours, and the active duration is about 6–10hrs.
*toxicity↝, Metformin use for an extended period is linked to a deficiency of vitamin B12.
*BioAv↑, Absolute bioavailability 50–60% in healthy individuals
*glucose↓, Conventionally, it is quite established that metformin lowers blood glucose primarily by its action on the liver
*AGEs↓, Metformin decreases the synthesis of AGE (“Advanced Glycation End”) product formation and hyperglycaemic-induced ROS (“Reactive Oxygen Species”) production
AntiCan↑, There is growing evidence that metformin has anti-cancer effects based on clinical and preclinical studies.
Risk↓, reported that metformin use might decrease the risk of lung cancer within T2D patients as compared to other conventional agents.
TumCP↓, Several studies on cancer cell lines have observed that metformin treatment leads to inhibition of development and proliferation and induces apoptosis of the cancer cells
Apoptosis↑,
TumCCA↑, Metformin was found to block the cell cycle in the “G(0)/G(1)” phase
cycD1/CCND1↓, and this was observed with a sharp drop in the cyclin D1 levels, pRb phosphorylation, and elevated p27(kip) expression.
pRB↓,
p27↓,
mTOR↓, as well as inhibits the mTOR pathway that is activated by insulin.
Casp↑, Metformin is also responsible for inducing caspase-dependent apoptosis along with c- JNK (“Jun N-Terminal Kinase”) activation, oxidative stress and mitochondrial depolarization.
ROS↑,
MMP↓,
ChemoSen↑, patients who received metformin along with the chemotherapy had better pathologic responses as compared to the group without metformin
*hepatoP↑, effects including cardioprotective, hepatoprotective, anti-malignant, and geroprotective effects
*CRM↑, mechanism behind the process of calorie restriction is a reduction in insulin
*Insulin↓,
*CRM↑, increased expression of PNC1 (pyrazinamidase/nicotinamidase 1), which encodes an enzyme that deaminates nicotinamide, is both necessary and sufficient for lifespan extension by calorie restriction and low-intensity stress.
*OS↑,
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*antiOx↓, Firstly, pterostilbene act as an antioxidant against various free radicals,
*ROS↑, reducing ROS production
*SOD↑, as well as increasing SOD and glutathione (GSH) activation via the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in neuronal cells [44].
*GSH↑,
*NRF2↑, by activating Nrf2
*MDA↓, pterostilbene reduced malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), aconitase-2 and 8-hydroxydeoxyguanosine (8-OHdG) level;
*HNE↓,
*Inflam↓, Pterostilbene has been reported as a potential anti-
inflammatory agent
*MAPK↓, pterostilbene inhibited mitogen-activated protein kinase (MAPK) activation and the production of pro-inflammatory cytokine (interleukin-6 [IL-6] and TNF-a)
*IL6↓,
*TNF-α↓,
*HO-1↑, through upregulating heme
oxygenase-1 (HO-1) to prevent hypoxic-ischemic brain injury
in neonatal rats
*cardioP↑, beneficial health effects of resveratrol and pterostilbene on cardioprotection, neuroprotection
*neuroP↑,
*CRM↑, as a calorie restriction mimic
*NLRP3↓, nhibiting pro-inflammatory cytokine such as IL-1b and NLRP3 inflammasome activation,
*AntiAge↑, Resveratrol produces changes associated with longer lifespan, including increased insulin sensitivity, reduced insulin-like growth factor-1 (IGF-I) levels, increased AMP-activated protein kinase (AMPK)
*IGF-1↓,
*AMPK↑,
*CRM↑, resveratrol opposed the effects of the high-calorie diet in 144 out of 153 significantly altered pathways.
*PGC-1α↑, activated receptor- γ coactivator 1α (PGC-1α) activity, increased mitochondrial number, and improved motor function.
*mtDam↓,
*motorD↑, Surprisingly, the resveratrol-fed HC mice steadily improved their motor skills as they aged
*hepatoP↑, At 18 months of age it was apparent that the high-calorie diet greatly increased the size and weight of livers and that resveratrol prevented these changes
*Dose↝, this study shows that an orally available small molecule at doses achievable in humans can safely reduce many of the negative consequences of excess caloric intake, with an overall improvement in health and survival.
*AMPK↑, In muscle, resveratrol activated AMPK, increased SIRT1 and PGC-1α protein levels,
*SIRT1↑, Resveratrol, which was discovered in a small-molecule screen as a potent SIRT1 activator
*PGC-1α↑,
*BP↓, Systolic blood pressure dropped and HOMA index improved after resveratrol.
*CRM↑, 30 days of resveratrol supplementation induces metabolic changes in obese humans, mimicking the effects of calorie restriction.
*Dose↝, resveratrol (150 mg/day (99%); resVida™)
*mtDam↓, Resveratrol increases AMPK activity, increases mitochondrial efficiency and respiration on fatty acid substrates.
*ALAT↓, paralleled by lower plasma ALAT values, as mentioned before, both indicating improved liver function.
*hepatoP↑,
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TumAuto↑, Spermidine has dual effects on cancers by targeting oncogenes, immunity, autophagy or apoptosis.
Apoptosis↑,
OS↑, Dietary spermidine intake has association with prolonged survival of cancer patients at the early stage.
CRM↑, increased uptake of spermidine as a caloric restriction mimic can reduce overall mortality associated with cancers.
TumCG⇅, Increased intake of polyamine seems to suppress tumorigenesis, but appears to accelerate the growth of established tumors.
cardioP↑, spermidine can protect from pathological events including two major death causes: cardiovascular disease (CVD) and cancer [15]
cognitive↑, and other aging-related diseases such as cognitive impairment during Alzheimer’s disease (AD) and Parkinson’s disease (PD)
*Dose⇅, spermidine at too high level could be detrimental to patients suffering from cancer, aging, innate immunity and cognitive impairment during AD and PD
*EP300↓, potent autophagy inducers including spermidine de facto act as EP300 inhibitors.
*mTORC1↓, simultaneously inhibit mTORC1.
*CRM↑, caloric restriction or intermediate fasting,7 continuous or intermittent medication of rapamycin,8, 9, 10 administration of the sirtuin 1-activator resveratrol,11, 12 external supply of the polyamine spermidine,
*HATs↓, Spermidine turned out to be an efficient inhibitor of histone acetyltransferases in vitro
*p62↓, Moreover, all the mentioned acetyltransferase inhibitors induced a significant reduction of p62/SQSTM1 levels,
*AntiAge↑, Spermidine retards the manifestation of several major age-associated diseases including arterial aging,36 colon cancer37 and neurodegenerative processes in mice
AntiCan↑,
Showing Research Papers: 1 to 15 of 15
* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 15
Pathway results for Effect on Cancer / Diseased Cells:
Redox & Oxidative Stress ⓘ
HO-1↓, 1, ROS↓, 1, ROS↑, 2,
Mitochondria & Bioenergetics ⓘ
MMP↓, 1,
Core Metabolism/Glycolysis ⓘ
ACLY↓, 1, AMPK↑, 1, CRM↑, 4, lipoGen↓, 1,
Cell Death ⓘ
Apoptosis↑, 2, Casp↑, 1, p27↓, 1,
Transcription & Epigenetics ⓘ
pRB↓, 1,
Autophagy & Lysosomes ⓘ
TumAuto↑, 2,
DNA Damage & Repair ⓘ
DNAdam↑, 1,
Cell Cycle & Senescence ⓘ
cycD1/CCND1↓, 1, TumCCA↑, 1,
Proliferation, Differentiation & Cell State ⓘ
IGF-1↓, 1, mTOR↓, 1, TumCG↓, 2, TumCG⇅, 1,
Migration ⓘ
TumCP↓, 1,
Immune & Inflammatory Signaling ⓘ
Inflam↓, 1, PGE2↓, 1,
Drug Metabolism & Resistance ⓘ
ChemoSen↑, 3, eff↑, 4, RadioS↑, 2,
Functional Outcomes ⓘ
AntiCan↑, 3, cardioP↑, 2, cognitive↑, 1, OS↑, 1, Risk↓, 2, toxicity∅, 1,
Total Targets: 32
Pathway results for Effect on Normal Cells:
Redox & Oxidative Stress ⓘ
antiOx↓, 1, antiOx↑, 2, Catalase↑, 1, GSH↑, 2, GSTs↑, 1, HNE↓, 1, HO-1↑, 2, lipid-P↓, 1, MDA↓, 2, NOX4↓, 1, NQO1↑, 1, NRF2↑, 3, ROS↓, 5, ROS↑, 1, ROS∅, 1, SOD↑, 2, SOD2↑, 1, TAC↑, 2, TrxR1↑, 1,
Mitochondria & Bioenergetics ⓘ
Insulin↓, 2, mtDam↓, 2, OCR↓, 1, PGC-1α↑, 2,
Core Metabolism/Glycolysis ⓘ
ALAT↓, 2, AMPK↑, 5, CRM↑, 11, glucose↓, 1, glyC↓, 1, LDL↓, 1, SIRT1↑, 2,
Cell Death ⓘ
iNOS↓, 1, MAPK↓, 1,
Transcription & Epigenetics ⓘ
HATs↓, 2,
Protein Folding & ER Stress ⓘ
NQO2↑, 1,
Autophagy & Lysosomes ⓘ
p62↓, 1,
Proliferation, Differentiation & Cell State ⓘ
EP300↓, 2, ERK↓, 1, IGF-1↓, 1, mTOR↓, 1, mTORC1↓, 1, STAT3↓, 1,
Migration ⓘ
VCAM-1↓, 1,
Angiogenesis & Vasculature ⓘ
NO↓, 1,
Immune & Inflammatory Signaling ⓘ
ICAM-1↓, 1, IL1↓, 1, IL1β↓, 1, IL6↓, 2, IL8↓, 1, Inflam↓, 4, NF-kB↓, 2, TLR2↓, 1, TLR4↓, 1, TNF-α↓, 3,
Synaptic & Neurotransmission ⓘ
AChE↓, 1,
Protein Aggregation ⓘ
AGEs↓, 1, NLRP3↓, 1,
Drug Metabolism & Resistance ⓘ
BioAv↑, 1, Dose⇅, 1, Dose↝, 2, Half-Life↝, 1,
Clinical Biomarkers ⓘ
ALAT↓, 2, BP↓, 3, creat↓, 1, IL6↓, 2,
Functional Outcomes ⓘ
AntiAge↑, 4, AntiDiabetic↑, 2, cardioP↑, 4, hepatoP↑, 3, motorD↑, 1, neuroP↑, 5, OS↑, 2, RenoP↑, 1, Strength↑, 1, toxicity⇅, 1, toxicity↝, 1, Weight↓, 1,
Total Targets: 76
Scientific Paper Hit Count for: CRM, Calorie restriction mimetics (CRMs)
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include :
-low or high Dose
-format for product, such as nano of lipid formations
-different cell line effects
-synergies with other products
-if effect was for normal or cancerous cells
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