| Features: |
| The (R)-enantiomer of alkannin is known as shikonin, and the racemic mixture of the two is known as shikalkin. Shikonin is a naphthoquinone derivative primarily isolated from the roots of plants in the Boraginaceae family (e.g., Lithospermum erythrorhizon). Shikonin is the main active component of a Chinese medicinal plant 'Zi Cao' -Shikonin is a major component of zicao (purple gromwell, the dried root of Lithospermum erythrorhizon), a Chinese herbal medicine with anti-inflammatory properties -Quinone methides (QMs) are highly reactive intermediates formed from natural compounds like shikonin -ic50 cancer cells 1-10uM, normal cells >10uM -known as Glycolysis inhibitor: ( inhibit pyruvate kinase M2 (PKM2*******), a key enzyme in the glycolytic pathway) Available from mcsformulas.com Shikonin Pro Liposomal, 30 mg Also In Glycolysis Inhibithree(100 mg PHLORIZIN,10 mg TANSHINONE IIA, 8 mg Shikonin) -Note half-life15-30mins or 8hr?. BioAv low, poor water solubility Pathways: - usually induce ROS production in cancer cells, and reduce ROS in normal cells. - ROS↑ related: MMP↓(ΔΨm), ER Stress↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓, - Lowers AntiOxidant defense in Cancer Cells: NRF2↓, TrxR↓**, SOD↓, GSH↓ Catalase↓ GPx4↓ - Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑, - lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : NLRP3↓, IL-1β↓, TNF-α↓, IL-6↓, IL-8↓ - inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, IGF-1↓, uPA↓, VEGF↓, FAK↓, NF-κB↓, TGF-β↓, ERK↓ - cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, - inhibits Migration/Invasion : TumCMig↓, TumCI↓, FAK↓, ERK↓, EMT↓, - inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, ECAR↓, OXPHOS↓, GRP78↑, GlucoseCon↓ - inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, EGFR↓, Integrins↓, - Others: PI3K↓, AKT↓, JAK↓, STAT↓, β-catenin↓, AMPK, ERK↓, JNK, P53↑, - Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective, - Selectivity: Cancer Cells vs Normal Cells |
| Source: |
| Type: effect |
| The Warburg effect is a metabolic phenomenon in which cancer cells preferentially use glycolysis for energy production, even in the presence of oxygen. Targeting the pathways involved in the Warburg effect is a promising strategy for cancer treatment. The Warburg effect is always accompanied by a hypoxic condition, and activation of HIF-1a contributes to the Warburg effect through coordinated upregulation of glycolysis and downregulation of oxidative phosphorylation. Warburg effect (GLUT1, LDHA, HK2, and PKM2). Here are some of the key pathways and potential targets: Note: use database Filter to find inhibitors: Ex pick target HIF1α, and effect direction ↓ 1.Glycolysis Inhibitors:(2-DG, 3-BP) -HK2 Inhibitors: such as 2-deoxyglucose, can reduce glycolysis -PFK1 Inhibitors: such as PFK-158, can reduce glycolysis -PFKFB Inhibitors: -PKM2 Inhibitors: (Shikonin) -Can reduce glycolysis -LDH Inhibitors: (Gossypol, FX11) -Reducing the conversion of pyruvate to lactate. -Inhibiting the production of ATP and NADH. -GLUT1 Inhibitors: (phloretin, WZB117) -A key transporter involved in glucose uptake. -GLUT3 Inhibitors: -PDK1 Inhibitors: (dichloroacetate) - A key enzyme involved in the regulation of glycolysis. 2.Gluconeogenesis pathway: -FBP1 Activators: can increase gluconeogenesis -PEPCK1 Inhibitors: can reduce gluconeogenesis 3.Pentose phosphate pathway: -G6PD Inhibitors: can reduce the pentose phosphate pathway 4.Mitochondrial metabolism: -MPC1 Inhibitors: can reduce mitochondrial metabolism and inhibit cancer -SDH Inhibitors: can reduce mitochondrial metabolism and inhibit cancer cell growth. 5.Hypoxia-inducible factor 1 alpha (HIF1α) pathway: -HIF1α inhibitors: (PX-478,Shikonin) -Reduce expression of glycolytic genes and inhibit cancer cell growth. 6.AMP-activated protein kinase (AMPK) pathway: -AMPK activators: (metformin,AICAR,berberine) -Can increase AMPK activity and inhibit cancer cell growth. 7.mTOR pathway: -mTOR inhibitors:(rapamycin,everolimus) -Can reduce mTOR activity and inhibit cancer cell growth. |
| 2356- | SK, | ESM1 enhances fatty acid synthesis and vascular mimicry in ovarian cancer by utilizing the PKM2-dependent warburg effect within the hypoxic tumor microenvironment |
| - | in-vitro, | Ovarian, | CaOV3 | - | in-vitro, | Ovarian, | OV90 | - | in-vivo, | NA, | NA |
| 2417- | SK, | Shikonin inhibits the Warburg effect, cell proliferation, invasion and migration by downregulating PFKFB2 expression in lung cancer |
| - | in-vitro, | Lung, | A549 | - | in-vitro, | Lung, | H446 |
| 2185- | SK, | Shikonin Inhibits Tumor Growth in Mice by Suppressing Pyruvate Kinase M2-mediated Aerobic Glycolysis |
| - | in-vitro, | Lung, | LLC1 | - | in-vitro, | Melanoma, | B16-BL6 | - | in-vivo, | NA, | NA |
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