肉盤菌內(nèi)酯
| 中文名稱 | 肉盤菌內(nèi)酯 |
|---|---|
| 中文同義詞 | 肉盤菌內(nèi)酯;半乳糖內(nèi)酯;伽利略內(nèi)酯;化合物 T22796;化合物 GALIELLALACTONE;加列拉內(nèi)酯 |
| 英文名稱 | galiellalactone |
| 英文同義詞 | galiellalactone;SOIISBQQYAGDKM-QJSROADHSA-N;(4S,5aR,7aR,7bS)-5,5a,6,7,7a,7b-Hexahydro-7b-hydroxy-4-methylindeno[1,7-bc]furan-2(4H)-one;Indeno[1,7-bc]furan-2(4H)-one, 5,5a,6,7,7a,7b-hexahydro-7b-hydroxy-4-methyl-, (4S,5aR,7aR,7bS)- |
| CAS號 | 133613-71-5 |
| 分子式 | C11H14O3 |
| 分子量 | 194.23 |
| EINECS號 | |
| 相關(guān)類別 | 微生物代謝物 |
| Mol文件 | 133613-71-5.mol |
| 結(jié)構(gòu)式 |  |
肉盤菌內(nèi)酯 性質(zhì)
| 沸點 | 400.7±38.0 °C(Predicted) |
|---|---|
| 密度 | 1.29±0.1 g/cm3(Predicted) |
| 儲存條件 | Store at -20°C |
| 溶解度 | DMSO:0.97(最大濃度 mg/mL);4.99(最大濃度 mM) 乙醇:0.97(最大濃度 mg/mL);4.99(最大濃度 mM) |
| 形態(tài) | 白色至淺褐色固體 |
| 酸度系數(shù)(pKa) | 12.48±0.40(Predicted) |
| 顏色 | White to off-white |
|
STAT3 250-500 nM (IC 50 ) |
Galiellalactone (2.5-25 μM; 24-72 hour) induces apoptosis of prostate cancer (PCa) cell lines expressingp-Stat3.
Galiellalactone (2.5-25 μM; 24-72 hour) decreases viability of DU145 cells.
Galiellalactone (10 μM) inhibits STAT3 signaling activity as assessed by luciferase reporter gene assay in IL-6-stimulated LNCaP cells.
Galiellalactone (10-100 μM; 1 hour) binds directly to STAT3 in DU145 cells .
Galiellalactone (5-50 μM; 1 hour) interferes with STAT3 DNA binding without inhibiting phosphorylation in DU145 cells .
Apoptosis Analysis
| Cell Line: | DU145, PC-3, and LNCaP cells |
| Concentration: | 0, 2.5, 5, 10, 25 μM |
| Incubation Time: | 24, 48, 72 hours |
| Result: | Induced an apoptotic response in PC-3 and DU145 cells. |
Cell Viability Assay
| Cell Line: | DU145 cells |
| Concentration: | 0, 2.5, 5, 10, 17.5, 25 μM |
| Incubation Time: | 24, 48, 72 hours |
| Result: | Decreased DU145 cells viability in a dose- and time-dependent manner. |
Western Blot Analysis
| Cell Line: | DU145 cells |
| Concentration: | 0, 10, 25 μM |
| Incubation Time: | 48 hours |
| Result: | Induced expression of the apoptotic marker cleaved caspase-3 and increased expression of cleaved PARP. |
Western Blot Analysis
| Cell Line: | DU145 cells |
| Concentration: | 0, 10, 25, 50, 100 μM |
| Incubation Time: | 1 hour |
| Result: | Prevented the binding of the biotinylated analogue of galiellalactone (GL-biot) to STAT3 in a dose-dependent manner demonstrating competitive binding. |
Western Blot Analysis
| Cell Line: | DU145 cells |
| Concentration: | 0, 5, 10, 25, 50 μM |
| Incubation Time: | 1 hour |
| Result: |
Inhibited STAT3 binding to DNA in a dose-dependent manner.
Did not affect phosphorylation of STAT3 Tyr-705 and Ser-727 or the expression of total STAT3. |
Galiellalactone (1, 3?mg/kg; daily i.p. for 3 weeks) inhibits PCa tumor growth in vivo.
| Animal Model: | Male nude NMR1 mice are injected PCa cell |
| Dosage: | 0, 1, 3?mg/kg |
| Administration: | Daily i.p. injections for 3 weeks |
| Result: | Reduced the tumor growth rate in DU145 xenografts by 41-42% and was well tolerated. |