| Properties | Information | |
|---|---|---|
| PhytoCAT-ID | PhytoCAT-50 | |
| Phytochemical name or plant extracts | Rhein | |
| PMID | 21457705 | |
| Literature evidence | Furthermore, Western blotting demonstrated that rhein inhibited heat shock protein 90alpha (Hsp90α) activity to induce degradation of Hsp90 client proteins including nuclear factor-kappa B (NF-κB), COX-2, and HER-2. | |
| IUPAC name | 4,5-dihydroxy-9,10-dioxoanthracene-2-carboxylic acid | |
| Phytochemicals’ class or type of plant extracts | Anthraquinone | |
| Source of phytochemicals or plant Extracts | Rheum palmatum | |
| Geographical availability | Belize, Bolivia, Brazil North, Brazil Northeast, Brazil Southeast, Brazil West-Central, Colombia, Costa Rica, Cuba, Dominican Republic, Ecuador, French Guiana, Guyana, Haiti, Honduras, Jamaica, Leeward Is., Mexico Southwest, Nicaragua, Panamá, Paraguay, Peru, Puerto Rico, Southwest Caribbean, Suriname, Trinidad-Tobago, Venezuela, Windward Is. | |
| Plant parts | Root | |
| Other cancers | Breast cancer, Liver cancer | |
| Target gene or protein | PI3K, p-AKT, p-ERK, Hsp90α, NF-κB, COX-2, HER-2, HIF-1α, VEGF(165), EGF, TNF-α, IL-6, I-κB, Caspase 9, CHOP, , eIF2α, GRP78, FOXO, Akt | |
| Gene or Protein evidence | Rhein inhibited in vitro angiogenesis by suppressing the activation of phosphatidylinositol 3-kinase (PI3K), phosphorylated-AKT (p-AKT) and phosphorylated extracellular signal-regulated kinase (p-ERK) but showed no inhibitory effects on total AKT or ERK. Rhein inhibited heat shock protein 90alpha (Hsp90α) activity to induce degradation of Hsp90 client proteins including nuclear factor-kappa B (NF-κB), COX-2, and HER-2. Rhein also inhibited the expression of hypoxia-inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor (VEGF(165)), epidermal growth factor (EGF), and the phosphorylation of inhibitor of NF-κB (I-κB) under normoxic or hypoxic conditions. The serum levels of TNF-α and IL-6 were significantly increased in the rhein and combination therapy groups. Rhein induced dose- and time-dependent manners increase in caspase-9-mediated apoptosis correlating with activation of ROS-mediated activation of NF-κB- and p53-signaling pathways in both cell types. Rhein induces CHOP expression, eIF2α phosphorylation and caspase cleavage, while it does not induce glucose-regulated protein 78 (GRP78) expression in both MCF-7 and HepG2 cells. Meanwhile, rhein inhibits thapsigargin-induced GRP78 expression and X box-binding protein 1 splicing. In addition, rhein inhibits Akt phosphorylation and stimulates FOXO transactivation activity. Rhein induces Bim expression in MCF-7 and HepG2 cells, which can be abrogated by FOXO3a knockdown. | |
| Target pathways | NF-κB- and p53-signaling pathways | |
| IC50 | 81.3 µM against MCF-7 52.1 µM against MDA-MB-435 | |
| Potency | Therefore, this study highlighted rhein as processing anti-proliferative activity against HER2 overexpression or HER2-basal expression in breast cancer cells and playing important roles in apoptotic induction of human breast cancer cells. Taken together, these data indicate that rhein is a promising anti-angiogenic compound for breast cancer cell viability and growth. Rhein induces apoptosis in human breast cancer cells. Rhein, a lipophilic anthraquinone, exhibits anti-inflammatory and anti-tumor activities; however, it is hepatotoxic. | |
| Cell line/ mice model | MCF-7, MDA-MB-435, MCF-7/HER2, MCF-7/VEC, MDA-MB-231, HepG2, 4T1 breast cancer xenografts in mice | |
| Additional information | In the presence of BCRP or MRP2 inhibitor, the permeability of rhein significantly decreased from B to A direction. In the MDCKII-BCRP cells, rhein was more permeable in B to A side than that in the opposite side. However, no significant differences of rhein permeability were observed in two directions in both MDCKII-MDR1 and MDCKII-MRP2 cells. Taken together, these results suggested that only BCRP was involved in rhein transport. Rhein inhibited vascular endothelial growth factor (VEGF(165))-stimulated human umbilical vein endothelial cell (HUVEC) tube formation, proliferation and migration under normoxic and hypoxic conditions. In addition, the proportion of CD8+ T cells in the spleen and tumour was significantly increased in the combination therapy group and was significantly different from the other treatment groups. Administration of rhein, atezolizumab, or their combination all had therapeutic effects on 4T1 breast cancer xenografts in mice, with the combination treatment having stronger effects. | |
| PubChem ID | 10168 | |
| Additional PMIDs | 14741736 25259860 31559608 32408623 18563353 29636785 33988779 23665409 21457705 22007260 19343002 | |
| Additional sources of information | https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:696772-1 | |
| Safety | NA |