Baicalin / PKM2 Cancer Research Results

BA, Baicalin: Click to Expand ⟱
Features:
Baicalin is a flavone glycoside, it is a flavonoid. It is the glucuronide of baicalein. Baicalin is a flavonoid glycoside derived from plants in the genus Scutellaria. It has anxiolytic, anti-cancer and anti-viral properties, and is used in traditional Chinese medicine.

Baicalein and baicalin are chemically related, with baicalin being essentially a conjugated (sugar-attached) form of baicalein. This conjugation can modify their biological functions and impacts, making them distinct in certain aspects even though they share several pharmacological properties.
baicalin is often hydrolyzed by gut β-glucuronidase to baicalein (aglycone) and then extensively converted to phase-II conjugates (glucuronides/sulfates), which constrains systemic “free” levels after oral dosing. In cancer models, baicalin/baicalein are reported to modulate NF-κB, PI3K/AKT/mTOR, MAPK, and related programs, with downstream effects on cell-cycle arrest, apoptosis, invasion/EMT, and angiogenesis (model-dependent).

Baicalein appears to be antioxidant in normal cells (low Cu). In vitro, baicalein can participate in copper-dependent redox cycling under high Cu conditions, leading to ROS generation. Whether this mechanism contributes meaningfully in vivo remains model-dependent. (higher Cu levels) (May applies to other plant polyphenols as well: Ex apigenin, luteolin, EGCG, and resveratrol).

Pathways:
Apoptosis Pathways (Intrinsic/Mitochondrial):
NF-κB Inhibition :
PI3K/Akt/mTOR Signaling Pathway downregulate :
MAPK/ERK and JNK Signaling Pathways:
STAT3 Signaling: (inhibit)
Wnt/β-Catenin Signaling Pathway: (suppress)
Other Pathways and Effects:
• Cell Cycle Arrests (commonly G0/G1 or G2/M)
• Anti-angiogenic Effects: By inhibiting VEGF
• Modulation of Oxidative Stress: Balancing reactive oxygen species (ROS) levels in cancer cells can also contribute to its antitumor effects.

• In normal cells or under conditions of oxidative stress, baicalin has been shown to act as an antioxidant.
• In cancer cells, baicalin may increase ROS levels, triggering apoptosis. Lower doses of baicalin might favor antioxidant responses, whereas higher concentrations could lead to ROS accumulation in cancer cells. Redox effects are concentration- and context-dependent; antioxidant behavior predominates in non-tumor oxidative stress models, whereas ROS increases have been reported in some tumor systems at higher concentrations.

• If copper levels are elevated in a cancer cell, the additional ROS generated via copper-mediated reactions may synergize with baicalin’s pro-oxidant effects (if observed at higher doses) to exceed the threshold for cancer cell survival.
• Conversely, in normal cells with tightly regulated copper levels, baicalin’s antioxidant properties may help in quenching excess ROS or maintaining redox balance.

-IC50 in cancer cell lines: Approximately 50–200 µM (with some variability depending on the cell type).

• IC50 in normal cell lines: Generally higher, often exceeding 200 µM, though values will vary with experimental conditions. Many in-vitro IC50 values exceed achievable systemic concentrations after oral dosing without advanced formulation.

Low oral bioavailability: classic rat PK reports very low absolute BA bioavailability and evidence of enterohepatic cycling

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 NF-κB inflammatory / survival transcription NF-κB ↓; COX-2/iNOS/cytokine programs ↓ (reported) Inflammation tone ↓ (common in injury models) R, G Anti-inflammatory + anti-survival transcription Frequently reported across inflammation and tumor models; strength depends on model/exposure and whether effects are driven by baicalein metabolites.
2 PI3K → AKT → mTOR survival axis PI3K/AKT/mTOR tone ↓ (reported; model-dependent) R, G Growth/survival modulation Often presented as a key “oncogenic survival” axis modulated by baicalin/baicalein; keep “reported/model-dependent.”
3 MAPK re-wiring (ERK / JNK / p38) MAPK modulation (context-dependent) P, R, G Signal reprogramming Directions vary across cell type, dose, and stress context; avoid fixed arrows without model-specific citations.
4 Nrf2/ARE antioxidant response (HO-1, GSH systems) Stress adaptation modulation (context-dependent) Nrf2 ↑; antioxidant defenses ↑ R, G Redox buffering Often described as antioxidant/anti-inflammatory; in tumors, Nrf2 direction/benefit is context-dependent.
5 Cell-cycle checkpoints (Cyclins/CDKs; S or G1/G2 arrest) Cell-cycle arrest ↑ (reported; phase varies) G Cytostasis Common phenotype-level endpoint; typically downstream of survival signaling changes.
6 Intrinsic apoptosis (mitochondrial/caspase linked) Apoptosis ↑; caspases ↑ (reported) ↔ (generally less activation) G Cell death execution Frequently reported in vitro; magnitude depends strongly on achievable intracellular exposure.
7 Invasion / metastasis programs (MMPs / EMT; Wnt/β-catenin reported) MMPs ↓; EMT/migration/invasion ↓ (reported) G Anti-invasive phenotype Often linked to NF-κB/PI3K/MAPK changes; Wnt/β-catenin modulation is reported in some systems.
8 Angiogenesis signaling (VEGF & related outputs) VEGF / angiogenic outputs ↓ (reported) G Anti-angiogenic support Usually a later phenotype-level effect tied to inflammatory/survival signaling modulation.
9 Autophagy modulation (stress adaptation) Autophagy ↑ or ↓ depending on model; can affect sensitivity to therapy G Adaptive stress response Reported in multiple cancer systems but direction is heterogeneous; keep model-qualified.
10 Bioavailability / metabolism constraint (baicalin ↔ baicalein; conjugates; enterohepatic cycling) Systemic “free” levels often low; extensive glucuronidation/sulfation Translation constraint Oral baicalin shows low absolute bioavailability in animal PK; gut microbiota hydrolysis to baicalein and extensive phase-II metabolism dominate exposure, with enterohepatic cycling reported.

Time-Scale Flag (TSF): P / R / G

  • P: 0–30 min (rapid signaling/redox interactions)
  • R: 30 min–3 hr (acute transcription + stress-response signaling shifts)
  • G: >3 hr (gene-regulatory adaptation and phenotype outcomes)


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


Scientific Papers found: Click to Expand⟱
2389- BA,    Baicalin alleviates lipid accumulation in adipocytes via inducing metabolic reprogramming and targeting Adenosine A1 receptor
- in-vitro, Obesity, 3T3
*ECAR↑, *OCR↓, *p‑AMPK↑, *p‑ACC↑, *Glycolysis↑, *lipidDe↓, *SREBP1↓, *FAO↑, *HK2↑, *PKM2↑, *LDHA↑, *PDKs↓, *ACC↓,

Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:


Total Targets: 0

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress

lipidDe↓, 1,  

Mitochondria & Bioenergetics

OCR↓, 1,  

Core Metabolism/Glycolysis

ACC↓, 1,   p‑ACC↑, 1,   p‑AMPK↑, 1,   ECAR↑, 1,   FAO↑, 1,   Glycolysis↑, 1,   HK2↑, 1,   LDHA↑, 1,   PDKs↓, 1,   PKM2↑, 1,   SREBP1↓, 1,  
Total Targets: 13

Scientific Paper Hit Count for: PKM2, Pyruvate Kinase, Muscle 2
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:%  Cells:%  prod#:39  Target#:772  State#:%  Dir#:2
wNotes=0 sortOrder:rid,rpid

 

Home Page