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| 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
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| Endonucleases are enzymes that play a crucial role in the maintenance of genome stability by cleaving the phosphodiester backbone of DNA. In the context of cancer, endonucleases can have both tumor-suppressing and tumor-promoting effects. 1. APEX1 (Apurinic/Apyrimidinic Endonuclease 1) Cancers: Breast cancer, lung cancer, colorectal cancer Prognosis: High expression is often associated with poor prognosis due to its role in DNA repair and resistance to chemotherapy. 2. FEN1 (Flap Endonuclease 1) Cancers: Breast cancer, prostate cancer, pancreatic cancer Prognosis: Overexpression is linked to increased tumor aggressiveness and poor survival rates. 3. EXO1 (Exonuclease 1) Cancers: Colorectal cancer, ovarian cancer Prognosis: High levels of EXO1 expression can correlate with poor prognosis and increased risk of metastasis. 4. DNase I (Deoxyribonuclease I) Cancers: Various solid tumors Prognosis: Altered expression levels can be indicative of tumor progression and immune evasion. 5. Caspase-3 (an endonuclease involved in apoptosis) Cancers: Various cancers, including leukemia and solid tumors Prognosis: High levels of active caspase-3 are often associated with increased apoptosis and may correlate with better treatment responses. 6. Rad51 (a recombinase with endonuclease activity) Cancers: Breast cancer, ovarian cancer Prognosis: Elevated expression is often linked to resistance to DNA-damaging therapies and poor prognosis. 7. MRE11 (part of the MRN complex) Cancers: Breast cancer, lung cancer Prognosis: Altered expression can indicate defects in DNA repair mechanisms, influencing treatment outcomes. 8. TDP1 (Tyrosyl-DNA Phosphodiesterase 1) Cancers: Glioblastoma, breast cancer Prognosis: High expression levels may be associated with resistance to certain chemotherapeutic agents. 9. UNG (Uracil-DNA Glycosylase) Cancers: Colorectal cancer, lung cancer Prognosis: Its expression can influence the mutation rate and may correlate with tumor aggressiveness. 10. LIG3 (DNA Ligase III) Cancers: Various cancers, including breast and prostate cancer Prognosis: Overexpression may be linked to enhanced DNA repair capabilities, contributing to treatment resistance. |
| 2227- | SK, | Shikonin induces mitochondria-mediated apoptosis and enhances chemotherapeutic sensitivity of gastric cancer through reactive oxygen species |
| - | in-vitro, | GC, | BGC-823 | - | in-vitro, | GC, | SGC-7901 | - | in-vitro, | Nor, | GES-1 |
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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