[CAS NO. 83182-58-5] 8α-Tigloyloxyhirsutinolide 13-O-acetate
PRODUCTS SPECIFICATIONS [83182-58-5]
DESCRIPTION [83182-58-5]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 420.45 |
| Molecular Formula | C22H28O8 |
| SMILES | O=C(/C(C)=C/C)O[C@@H](C[C@H]1C)C(/C(OC2=O)=C\[C@](O[C@]13O)(CC3)C)=C2COC(C)=O |
Summary
8α-Tigloyloxyhirsutinolide 13-O-acetate is a potent and orally active STAT3 inhibitor. 8α-Tigloyloxyhirsutinolide 13-O-acetate induces early oxidative stress and pyroptosis , and late DNA damage, cell cycle arrest, apoptosis in the TNBC cells. 8α-Tigloyloxyhirsutinolide 13-O-acetate suppresses tumor cell growth in vitro and tumor growth in vivo [1] [2] .
IC50 & Target
|
STAT3 |
Bcl-2 |
Bcl-xL |
Mcl-1 |
In Vitro
8α-Tigloyloxyhirsutinolide 13-O-acetate (R001) (0-30 μM, 72 h) dose-dependently suppresses the viable cell numbers of the human cancer lines
[1]
.
8α-Tigloyloxyhirsutinolide 13-O-acetate (0-10 μM, 0-24 h) leads to early pyroptosis and late DNA damage, cell cycle arrest, and apoptosis only in the TNBC cells
[1]
.
8α-Tigloyloxyhirsutinolide 13-O-acetate (0-20 μM, 0-48 h) promotes ROS induction in triple-negative breast cancer cells
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Proliferation Assay [1]
| Cell Line: | Multiple human cancer lines, normal human breast epithelial cells and normal human brain microvascular endothelial cells (HBMEC) |
| Concentration: | 0, 1, 2.5, 5, 10, 20, 30 μM |
| Incubation Time: | 72 h |
| Result: | Dose-dependently suppressed the viable cell numbers of the human cancer lines, MDA-MB-468, MDA-MB-231, Panc-1, A549, DU145, HCC1937, and MDA-MB-436 cells with IC 50 values of 2.3, 4.4, 4.3, 5.2, 5.8, 6.3, and 7.1 µM, respectively, compared to much weaker effects on the normal human breast epithelial cells, MCF-10A or HBMEC, with IC 50 of 23.9 or 14.2 µM, respectively. |
Western Blot Analysis [1]
| Cell Line: | NIH3T3/v-Src fibroblasts, MDA-MB-231, MDA-MB-468, or MCF-10A cells |
| Concentration: | 0, 2, 5, 10, 20 μM |
| Incubation Time: | 30 min, 3 h, 24 h |
| Result: | Suppressed STAT3:STAT3 DNA-binding activity, with IC 50 of 5 µM. Showed the inhibition of STAT3 Tyr phosphorylation in time- and dose-dependent manner, while phospho-Ser-STAT3 (pS727-STAT3), pY1068EGFR, and pY-Jak2 were largely unaffected. Attenuated the expression of STAT3 downstream target genes, including c-Myc, Mcl-1, Bcl-2, Bcl-xL, and vascular endothelial growth factor (VEGF) in MDA-MB-468 and MDA-MB-231 cells. |
Apoptosis Analysis [1]
| Cell Line: | Triple-negative breast cancer (TNBC), MDA-MB-231 and MDA-MB-468 cells, or normal human breast epithelial cells, MCF-10A |
| Concentration: | 0, 2.5, 5 or 10 µM |
| Incubation Time: | 6 or 24 h |
| Result: | Showed no significant induction of early apoptosis at 6 h, while the evidence of extensive cell death of 56.2% occurred at later time (24 h), with cleavage of poly (ADP-ribose) polymerase (PARP) and caspase 3 at 24-48 h. |
In Vivo
8α-Tigloyloxyhirsutinolide 13-O-acetate (5 mg/kg, Oral gavage, 5 times per week for 75 days) suppresses tumor growth in mice [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Five-week-old female athymic nude mice (injected subcutaneously in the right flank area with MDA-MB-468 cells in 100 μL PBS) |
| Dosage: | 5 mg/kg |
| Administration: | Oral gavage, every day, 5 times per week for 75 days |
| Result: | Inhibited MDA-MB-468 xenografts growth in mice, with reduced pY705-STAT3, G6PD, TrxR1, and GSH levels. |
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
References
- [1] Zhu Y, et al. Natural product preferentially targets redox and metabolic adaptations and aberrantly active STAT3 to inhibit breast tumor growth in vivo. Cell Death Dis. 2022 Dec 6;13(12):1022.
- [2] A Bardón, et al. Glaucolides and related sesquiterpene lactones fromVernonia nudiflora and Chrysolaena propinqua. Phytochemistry, 1992, 31(2):609-613.