| Properties | Information | |
|---|---|---|
| PhytoCAT-ID | PhytoCAT-2114 | |
| Phytochemical name or plant extracts | Pachymic acid | |
| PMID | 30381614 | |
| Literature evidence | Molecular docking and enzyme assay revealed that PA is a competing activator of PKM2, and mimics the natural activator, fructose-1,6-bisphosphate. | |
| IUPAC name | (2R)-2-[(3S,5R,10S,13R,14R,16R,17R)-3-acetyloxy-16-hydroxy-4,4,10,13,14-pentamethyl-2,3,5,6,7,11,12,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-17-yl]-6-methyl-5-methylideneheptanoic acid | |
| Phytochemicals’ class or type of plant extracts | Triterpenoid | |
| Source of phytochemicals or plant Extracts | Poria cocos | |
| Geographical availability | NA | |
| Plant parts | Mushroom | |
| Other cancers | Breast cancer, Prostate cancer, Lung cancer, Bladder cancer | |
| Target gene or protein | Cyclin D1, Cyclin E, CDK2, CDK4, p53, p21, Bcl-2, Bax, Cyt-c, Caspase 3, Caspase 8, Caspase 9, MMP9, PKM2 | |
| Gene or Protein evidence | The expression of cell cycle-associated cyclin D1, cyclin E, CDK2, and CDK4 were downregulated, while p53 and p21 expression were upregulated following the PA treatment. In addition, PA downregulated the apoptotic regulator Bcl-2, increased the expression of pro-apoptotic protein Bax, and promoted the release of cytochrome c and the activation of cleaved caspase-3, -9 and caspase -8 via mitochondria-mediated and death receptor-mediated signaling pathways. Taken together, it was concluded that by targeting NF-κB signaling, PA inhibited breast cancer cell invasion through decreasing MMP-9 expression. PA may thus be potentially exploited for use in tumor metastasis intervention. Molecular docking and enzyme assay revealed that PA is a competing activator of PKM2, and mimics the natural activator, fructose-1,6-bisphosphate. | |
| Target pathways | Mitochondria-mediated and death receptor-mediated signaling pathways NF-κB signaling | |
| IC50 | 2.13 ± 0.24 μg/mL against MDA-MB-231 | |
| Potency | The data also suggested that PA could be developed as an efficacious agent for breast cancer treatment with less side effects. However, decreased glucose uptake and lactate production after PA treatment was observed in SK-BR-3 breast carcinoma cells, indicating a blockage or downregulation of glycolysis. | |
| Cell line/ mice model | SKBR-3, BALB/c nude mice/MDA-MB-231 | |
| Additional information | NA | |
| PubChem ID | 5484385 | |
| Additional PMIDs | 32283190 20521099 28856634 | |
| Additional sources of information | In accord with the luciferase activity data, western blot analysis showed that PA inhibited NF-κB signaling pathway, but did not alter the phosphorylation states of mitogen-activated protein kinases including ERK, JNK, and p38 kinase. The inhibition of PA on NF-κB signaling pathway was further attributed to PA-mediated diminution in PMA-induced degradation of inhibitor of kappaBα (IκBα) through preventing phosphorylation of the upstream signal IκB kinase (IKK). A decrease in p65 nuclear translocation was achieved, which led to attenuation of NF-κB transactivation. | |
| Safety | Pachymic acid (PA), separated and identified as the most active compound, induced the significant cytotoxicity on breast cancer cells MDA-MB-231(IC50 value, 2.13 ± 0.24 μg/mL) and was not active against the normal breast epithelium cells MCF-10A. |