Phenoxodiol (Idronoxil) 是一种合成的 Genestein 的类似物，激活线粒体caspase系统，抑制 XIAP (一个凋亡抑制剂)，使癌细胞对 Fas 介导的凋亡敏感。Phenoxodiol 还通过稳定可分裂复合物抑制 DNA 拓扑异构酶 II (DNA topoisomerase II)，从而阻止 DNA 复制。Phenoxodiol 在细胞周期的 G1/S 期诱导细胞周期阻滞，通过独立于 p53 的方式上调 p21WAF1。
| 生物活性 | Phenoxodiol (Idronoxil), a synthetic analog of Genestein, activates the mitochondrialcaspasesystem, inhibitsXIAP(anapoptosisinhibitor), and sensitizes thecancercells to Fas-mediatedapoptosis. Phenoxodiol also inhibitsDNAtopoisomeraseIIby stabilizing thecleavablecomplex. Phenoxodiol induces cell cycle arrest in the G1/S phase of the cell cycle and upregulates p21WAF1via a p53 independent manner[1][2]. |
| IC50& Target | Caspase, DNA topoisomerase II[1][2]. |
体外研究
(In Vitro) | Phenoxodiol (Idronoxil) (0-10 μg/mL; 24 h) decreases cell viability of primary ovarian cancer cells[1].
Phenoxodiol (0-10 μg/mL; 24 h) induces apoptosis and restores sensitivity to Fas-mediated apoptosis in ovarian cancer cells[1].
Phenoxodiol (0-10 μg/mL; 24 h) induces caspase-8 activation and FLIP downregulation through the Akt-pathway. Phenoxodiol-induced apoptosis involves activation of the mitochondrial pathway and is caspase dependent. Phenoxodiol treatment results in downregulation and cleavage of XIAP[1].
Phenoxodiol (10 and 30 μM; 24 and 48 h) induces cell cycle arrest in the G1/S phase of the cell cycle in prostate cancer cells[2].
Cell Viability Assay[1] | Cell Line: | R182s, R127, Hey, CP70, A2780, R187, R188, R207 and OSE cells | | Concentration: | 0, 0.01, 0.1, 1 and 10 μg/mL | | Incubation Time: | 24 h | | Result: | A significant decrease in cell viabilityin all the ovarian cancer cell cultures was observed at a concentration of 10 μg/mL (41.6 μM) and did not affect ovarian surface epithelial (OSE) cells’ viability. In CP70 cells, the IC50was 1.35 μM. |
Apoptosis Analysis[1] | Cell Line: | CP70 and OSE cells | | Concentration: | 10 μg/mL | | Incubation Time: | 24 h | | Result: | Induced apoptosis and resulted in a twofold increase in caspase-3 activity. No change in
caspase-3 activity was found in normal OSE cells. |
Western Blot Analysis[1] | Cell Line: | Ovarian cancer cells | | Concentration: | 10 μg/mL | | Incubation Time: | 24 h | | Result: | Induced caspase-8 activation, characterized bycleavage of procaspase-8 into its p43/41 and
p28 forms and in downregulation of the p43 form of FLIPC in all the primarycultures as well as in the CP70 and Hey cell lines. Decreased the levels of Akt expression. Resulted in XIAP downregulation and cleavage to its 30 kDa inactive form. |
Cell Cycle Analysis[2] | Cell Line: | LNCaP, DU145 and PC3 cells | | Concentration: | 10 and 30 μM | | Incubation Time: | 24 and 48 h | | Result: | Induced significantly decreased G2 phase cell populations versus DMSO vehicle control, over 24 hours for both 10 μM and 30 μM treatments. The S phase cell population was found to increase versus DMSO vehicle control. |
RT-PCR[2] | Cell Line: | LNCaP, DU145 and PC3 cells | | Concentration: | 10 and 30 μM | | Incubation Time: | 24 and 48 h | | Result: | PC3 cells were found to significantly increase the expression ofc-Mycat 30 μM after 48 h. Decreased the expression ofCyclin-D1after 24 hours of treatment with 30 μM in DU145 and PC3 cells. Decreased the expression ofKi-67after 24 hours of treatment with 10 and 30 μM in LNCaP and PC3 cells. Increased the expression ofp21in LNCaP and PC3 cells. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : ≥ 100 mg/mL(416.23 mM) H2O : 1 mg/mL(4.16 mM;Need ultrasonic) *"≥" means soluble, but saturation unknown. 配制储备液 | 1 mM | 4.1623 mL | 20.8117 mL | 41.6233 mL | | 5 mM | 0.8325 mL | 4.1623 mL | 8.3247 mL | | 10 mM | 0.4162 mL | 2.0812 mL | 4.1623 mL |
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储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
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此方案可获得 ≥ 2.5 mg/mL (10.41 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.5 mg/mL (10.41 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (10.41 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 3. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (10.41 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (10.41 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。 *以上所有助溶剂都可在本网站选购。
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