PKM2 Cancer Research Results

PKM2, Pyruvate Kinase, Muscle 2: Click to Expand ⟱
Source:
Type: enzyme
PKM2 (Pyruvate Kinase, Muscle 2) is an enzyme that plays a crucial role in glycolysis, the process by which cells convert glucose into energy. PKM2 is a key regulatory enzyme in the glycolytic pathway, and it is primarily expressed in various tissues, including muscle, brain, and cancer cells.
-C-myc is a common oncogene that enhances aerobic glycolysis in the cancer cells by transcriptionally activating GLUT1, HK2, PKM2 and LDH-A
-PKM2 has been shown to be overexpressed in many types of tumors, including breast, lung, and colon cancer. This overexpression may contribute to the development and progression of cancer by promoting glycolysis and energy production in cancer cells.
-inhibition of PKM2 may cause ATP depletion and inhibiting glycolysis.
-PK exists in four isoforms: PKM1, PKM2, PKR, and PKL
-PKM2 plays a role in the regulation of glucose metabolism in diabetes.
-PKM2 is involved in the regulation of cell proliferation, apoptosis, and autophagy.
– Pyruvate kinase catalyzes the final, rate-limiting step of glycolysis, converting phosphoenolpyruvate (PEP) to pyruvate with the production of ATP.
– The PKM2 isoform is uniquely regulated and can exist in both highly active tetrameric and less active dimeric forms.
– Cancer cells often favor the dimeric form of PKM2 to slow pyruvate production, thereby accumulating upstream glycolytic intermediates that can be diverted into anabolic pathways to support cell growth and proliferation.
– Under low oxygen conditions, cancer cells rely on altered metabolic pathways in which PKM2 is a key player. – The shift to aerobic glycolysis (Warburg effect) orchestrated in part by PKM2 helps tumor cells survive and grow in hypoxic conditions.

– Elevated expression of PKM2 is frequently observed in many cancer types, including lung, breast, colorectal, and pancreatic cancers.
– High levels of PKM2 are often correlated with enhanced tumor aggressiveness, poor differentiation, and advanced clinical stage.

PKM2 in carcinogenesis and oncotherapy

Inhibitors of PKM2:
-Shikonin, Resveratrol, Baicalein, EGCG, Apigenin, Curcumin, Ursolic Acid, Citrate (best known as an allosteric inhibitor of phosphofructokinase-1 (PFK-1), a key rate-limiting enzyme in glycolysis) potential to directly inhibit or modulate PKM2 is less well established

Full List of PKM2 inhibitors from Database
-key connected observations: Glycolysis↓, lactateProd↓, ROS↑ in cancer cell, while some result for opposite effect on normal cells.
Tumor pyruvate kinase M2 modulators

Flavonoids effect on PKM2
Compounds name IC50/AC50uM Effect
Flavonols
1. Fisetin 0.90uM Inhibition
2. Rutin 7.80uM Inhibition
3. Galangin 8.27uM Inhibition
4. Quercetin 9.24uM Inhibition
5. Kaempferol 9.88uM Inhibition
6. Morin hydrate 37.20uM Inhibition
7. Myricetin 0.51uM Activation
8. Quercetin 3-b- D-glucoside 1.34uM Activation
9. Quercetin 3-D -galactoside 27-107uM Ineffective
Flavanons
10. Neoeriocitrin 0.65uM Inhibition
11. Neohesperidin 14.20uM Inhibition
12. Naringin 16.60uM Inhibition
13. Hesperidin 17.30uM Inhibition
14. Hesperitin 29.10uM Inhibition
15. Naringenin 70.80uM Activation
Flavanonols
16. (-)-Catechin gallateuM 0.85 Inhibition
17. (±)-Taxifolin 1.16uM Inhibition
18. (-)-Epicatechin 1.33uM Inhibition
19. (+)-Gallocatechin 4-16uM Ineffective
Phenolic acids
20. Ferulic 11.4uM Inhibition
21. Syringic and 13.8uM Inhibition
22. Caffeic acid 36.3uM Inhibition
23. 3,4-Dihydroxybenzoic acid 78.7uM Inhibition
24. Gallic acid 332.6uM Inhibition
25. Shikimic acid 990uM Inhibition
26. p-Coumaric acid 22.2uM Activation
27. Sinapinic acids 26.2uM Activation
28. Vanillic 607.9uM Activation


BC, Breast Cancer: Click to Expand ⟱
Breast Cancer
Scientific Papers found: Click to Expand⟱
3434- ALA,    Alpha lipoic acid modulates metabolic reprogramming in breast cancer stem cells enriched 3D spheroids by targeting phosphoinositide 3-kinase: In silico and in vitro insights
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
tumCV↓, PI3K↓, p‑Akt↓, p‑P70S6K↓, mTOR↓, ATP↓, GlucoseCon↓, ROS↑, PKM2↓, LDHA↓, Glycolysis↓, ChemoSen↑,
3436- ALA,    Alpha lipoic acid modulates metabolic reprogramming in breast cancer stem cells enriched 3D spheroids by targeting phosphoinositide 3-kinase: In silico and in vitro insights Author links open overlay panel
- in-vitro, BC, MCF-7
ChemoSen↑, PI3K↓, Akt↓, ATP↓, GlucoseCon↓, ROS↑, PKM2↓, Glycolysis↓, CSCs↓, IGF-1R↓, Furin↓, RadioS↑,
2388- Ash,    Withaferin A decreases glycolytic reprogramming in breast cancer
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, MDA-MB-468 - in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-453
GlucoseCon↓, lactateProd↓, ATP↓, Glycolysis↓, GLUT1↓, HK2↓, PKM2↓, cMyc↓, Warburg↓, cMyc↓,
2304- CUR,    Curcumin decreases Warburg effect in cancer cells by down-regulating pyruvate kinase M2 via mTOR-HIF1α inhibition
- in-vitro, Lung, H1299 - in-vitro, BC, MCF-7 - in-vitro, Cerv, HeLa - in-vitro, Pca, PC3 - in-vitro, Nor, HEK293
Glycolysis↓, GlucoseCon↓, lactateProd↓, PKM2↓, mTOR↓, Hif1a↓, selectivity↑, Dose↝, tumCV↓,
2305- CUR,    Mitochondrial targeting nano-curcumin for attenuation on PKM2 and FASN
- in-vitro, BC, MCF-7
BioAv↑, PKM2↓, FASN↓, Glycolysis↓,
2352- dietFMD,    Glucose restriction reverses the Warburg effect and modulates PKM2 and mTOR expression in breast cancer cell lines
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, MCF-7
Warburg↓, mTOR↓, PKM2↓,
2379- MET,    Down‐regulation of PKM2 enhances anticancer efficiency of THP on bladder cancer
- in-vitro, Bladder, T24/HTB-9 - in-vitro, BC, UMUC3
PKM2↓, p‑STAT3↓, TumCG↓, eff↑, chemoP↑, AMPK↑,
2374- MET,    Metformin Induces Apoptosis and Downregulates Pyruvate Kinase M2 in Breast Cancer Cells Only When Grown in Nutrient-Poor Conditions
- in-vitro, BC, MCF-7 - in-vitro, BC, SkBr3 - in-vitro, BC, MDA-MB-231
eff↑, Apoptosis↑, Glycolysis↓, PKM2↓, mTOR↓, PARP↓,
1231- PBG,    Caffeic acid phenethyl ester inhibits MDA-MB-231 cell proliferation in inflammatory microenvironment by suppressing glycolysis and lipid metabolism
- in-vitro, BC, MDA-MB-231
TumCP↓, TumCMig↓, TumCI↓, MMP↓, TLR4↓, TNF-α↓, NF-kB↓, IL1β↓, IL6↓, IRAK4↓, GLUT1↓, GLUT3↓, HK2↓, PFK↓, PKM2↓, LDHA↓, ACC↓, FASN↓, eff↓,
1672- PBG,    The Potential Use of Propolis as an Adjunctive Therapy in Breast Cancers
- Review, BC, NA
ChemoSen↓, RadioS↑, Inflam↓, AntiCan↑, Dose∅, mtDam↑, Apoptosis?, OCR↓, ATP↓, ROS↑, ROS↑, LDH↓, TP53↓, Casp3↓, BAX↓, P21↓, ROS↑, eNOS↑, iNOS↑, eff↑, hTERT/TERT↓, cycD1/CCND1↓, eff↑, eff↑, eff↑, eff↑, STAT3↓, TIMP1↓, IL4↓, IL10↓, OS↑, Dose∅, ER Stress↑, ROS↑, NF-kB↓, p65↓, MMP↓, TumAuto↑, LC3II↑, p62↓, TLR4↓, mtDam↑, LDH↓, ROS↑, Glycolysis↓, HK2↓, PFK↓, PKM2↓, LDH↓, IL10↓, HDAC8↓, eff↑, eff↑, P21↑,
2381- PBG,    Chinese Poplar Propolis Inhibits MDA-MB-231 Cell Proliferation in an Inflammatory Microenvironment by Targeting Enzymes of the Glycolytic Pathway
- in-vitro, BC, MDA-MB-231
TumCP↓, TumCMig↓, TumCI↓, angioG↓, TNF-α↓, IL1β↓, IL6↓, NLRP3↓, Glycolysis↓, HK2↓, PFK↓, PKM2↓, LDHA↓, ROS↑, MMP↓,
2409- PTS,    Pterostilbene Induces Pyroptosis in Breast Cancer Cells through Pyruvate Kinase 2/Caspase-8/Gasdermin C Signaling Pathway
- in-vitro, BC, EMT6 - in-vitro, BC, 4T1 - in-vitro, Nor, HC11
Pyro↑, Glycolysis↓, *toxicity∅, selectivity↑, GSDMC↑, PKM2↓, PKM1↑, GlucoseCon↓, lactateProd↓, ATP↓, TumCG↓,
2341- QC,    Quercetin suppresses the mobility of breast cancer by suppressing glycolysis through Akt-mTOR pathway mediated autophagy induction
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231 - in-vivo, NA, NA
MMP2↓, MMP9↓, VEGF↓, Glycolysis↓, lactateProd↓, PKM2↓, GLUT1↓, LDHA↓, TumAuto↑, Akt↓, mTOR↓, TumMeta↓, MMP3↓, eff↓, GlucoseCon↓, lactateProd↓, TumAuto↑, LC3B-II↑,
2330- RES,    Resveratrol Induces Cancer Cell Apoptosis through MiR-326/PKM2-Mediated ER Stress and Mitochondrial Fission
- in-vitro, CRC, DLD1 - in-vitro, Cerv, HeLa - in-vitro, BC, MCF-7
TumCP↓, Apoptosis↑, PKM2↓, ER Stress↑,
2328- RES,    Resveratrol Inhibits Cancer Cell Metabolism by Down Regulating Pyruvate Kinase M2 via Inhibition of Mammalian Target of Rapamycin
- in-vitro, Cerv, HeLa - in-vitro, Liver, HepG2 - in-vitro, BC, MCF-7
PKM2↓, mTOR↓, GlucoseCon↓, lactateProd↓,
2445- SFN,    Sulforaphane-Induced Cell Cycle Arrest and Senescence are accompanied by DNA Hypomethylation and Changes in microRNA Profile in Breast Cancer Cells
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231 - in-vitro, BC, SkBr3
TumCCA↑, P21↑, p27↑, NO↑, Akt↓, ATP↓, AMPK↑, TumAuto↑, DNMT1↓, HK2↓, PKM2↓, HDAC3↓, HDAC4↓, HDAC8↓,
2306- SIL,  CUR,  RES,  EA,    Identification of Natural Compounds as Inhibitors of Pyruvate Kinase M2 for Cancer Treatment
- in-vitro, BC, MDA-MB-231
PKM2↓, Dose↝, Dose↝,
2187- SK,  VitK3,    Shikonin, vitamin K3 and vitamin K5 inhibit multiple glycolytic enzymes in MCF-7 cells
- in-vitro, BC, MCF-7
Glycolysis↓, PKM2↓,
2181- SK,    Shikonin and its analogs inhibit cancer cell glycolysis by targeting tumor pyruvate kinase-M2
- in-vitro, BC, MCF-7 - in-vitro, Lung, A549 - in-vitro, Cerv, HeLa
Glycolysis↓, lactateProd↓, GlucoseCon↓, PKM2↓, LDH∅,
2350- UA,    Ursolic acid-mediated changes in glycolytic pathway promote cytotoxic autophagy and apoptosis in phenotypically different breast cancer cells
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
Akt↓, Glycolysis↓, HK2↓, PKM2↓, ATP↓, lactateProd↓, AMPK↑, TumAuto↑, Apoptosis↑, ERK↓, MMP↓, NO↑, ROS↑, DNAdam↑,
2414- β‐Ele,    Beta‐elemene inhibits breast cancer metastasis through blocking pyruvate kinase M2 dimerization and nuclear translocation
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, MCF-7 - in-vivo, NA, NA
TumCMig↓, TumCI↓, TumMeta↓, Glycolysis↓, GlucoseCon↓, lactateProd↓, PKM2↓, EGFR↓, GLUT1↓, LDHA↓, ECAR↓, OCR↓,

Showing Research Papers: 1 to 21 of 21

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 21

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

ROS↑, 9,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 7,   MMP↓, 4,   mtDam↑, 2,   OCR↓, 2,  

Core Metabolism/Glycolysis ⓘ

ACC↓, 1,   AMPK↑, 3,   cMyc↓, 2,   ECAR↓, 1,   FASN↓, 2,   GlucoseCon↓, 9,   Glycolysis↓, 14,   HK2↓, 6,   lactateProd↓, 9,   LDH↓, 3,   LDH∅, 1,   LDHA↓, 5,   PFK↓, 3,   PKM1↑, 1,   PKM2↓, 21,   Warburg↓, 2,  

Cell Death ⓘ

Akt↓, 4,   p‑Akt↓, 1,   Apoptosis?, 1,   Apoptosis↑, 3,   BAX↓, 1,   Casp3↓, 1,   GSDMC↑, 1,   hTERT/TERT↓, 1,   iNOS↑, 1,   p27↑, 1,   Pyro↑, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 2,  

Protein Folding & ER Stress ⓘ

ER Stress↑, 2,  

Autophagy & Lysosomes ⓘ

LC3B-II↑, 1,   LC3II↑, 1,   p62↓, 1,   TumAuto↑, 5,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   DNMT1↓, 1,   PARP↓, 1,   TP53↓, 1,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 1,   P21↓, 1,   P21↑, 2,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

CSCs↓, 1,   ERK↓, 1,   HDAC3↓, 1,   HDAC4↓, 1,   HDAC8↓, 2,   IGF-1R↓, 1,   mTOR↓, 6,   p‑P70S6K↓, 1,   PI3K↓, 2,   STAT3↓, 1,   p‑STAT3↓, 1,   TumCG↓, 2,  

Migration ⓘ

Furin↓, 1,   MMP2↓, 1,   MMP3↓, 1,   MMP9↓, 1,   TIMP1↓, 1,   TumCI↓, 3,   TumCMig↓, 3,   TumCP↓, 3,   TumMeta↓, 2,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   EGFR↓, 1,   eNOS↑, 1,   Hif1a↓, 1,   NO↑, 2,   VEGF↓, 1,  

Barriers & Transport ⓘ

GLUT1↓, 4,   GLUT3↓, 1,  

Immune & Inflammatory Signaling ⓘ

IL10↓, 2,   IL1β↓, 2,   IL4↓, 1,   IL6↓, 2,   Inflam↓, 1,   IRAK4↓, 1,   NF-kB↓, 2,   p65↓, 1,   TLR4↓, 2,   TNF-α↓, 2,  

Protein Aggregation ⓘ

NLRP3↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 1,   ChemoSen↓, 1,   ChemoSen↑, 2,   Dose↝, 3,   Dose∅, 2,   eff↓, 2,   eff↑, 9,   RadioS↑, 2,   selectivity↑, 2,  

Clinical Biomarkers ⓘ

EGFR↓, 1,   hTERT/TERT↓, 1,   IL6↓, 2,   LDH↓, 3,   LDH∅, 1,   TP53↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   chemoP↑, 1,   OS↑, 1,  
Total Targets: 104

Pathway results for Effect on Normal Cells:


Functional Outcomes ⓘ

toxicity∅, 1,  
Total Targets: 1

Scientific Paper Hit Count for: PKM2, Pyruvate Kinase, Muscle 2
3 Curcumin
3 Propolis -bee glue
3 Resveratrol
2 Alpha-Lipoic-Acid
2 Metformin
2 Shikonin
1 Ashwagandha(Withaferin A)
1 diet FMD Fasting Mimicking Diet
1 Pterostilbene
1 Quercetin
1 Sulforaphane (mainly Broccoli)
1 Silymarin (Milk Thistle) silibinin
1 Ellagic acid
1 VitK3,menadione
1 Ursolic acid
1 β‐Elemene
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

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:4  Cells:%  prod#:%  Target#:772  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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