| Properties | Information | |
|---|---|---|
| PhytoCAT-ID | PhytoCAT-1560 | |
| Phytochemical name or plant extracts | Salvicine | |
| PMID | 16024664 | |
| Literature evidence | In this study, we investigated whether salvicine altered the levels of ROS in breast cancer MCF-7 cells and whether these ROS contributed to the observed antitumoral activity. | |
| IUPAC name | 8-(3,4-dihydroxy-4-methylpentyl)-7-methyl-3-propan-2-ylnaphthalene-1,2-dione | |
| Phytochemicals’ class or type of plant extracts | Diterpenoid quinone | |
| Source of phytochemicals or plant Extracts | Chinese herb | |
| Geographical availability | China | |
| Plant parts | NA | |
| Other cancers | Breast cancer | |
| Target gene or protein | topo II, mdr-1, Bcl-2, p38 MAPK, ERK, DNA-dependent kinase (DNA-PK(CS)) | |
| Gene or Protein evidence | Salvicine, a novel topoisomerase II inhibitor, exerts its potent anticancer activity by ROS generation. These results suggest that the reduction of mdr-1 and bcl-2 expression by salvicine possibly contributes to its cytotoxicity and apoptotic induction in this system. These findings contribute to a better understanding of the antimetastatic activity of salvicine and shed new light on the complex roles of ROS and downstream signaling molecules, particularly p38 MAPK, in the regulation of integrin function and cell adhesion. Conversely, salvicine induced extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) phosphorylation. On the other hand, when examining the impact of salvicine on DNA repair pathways, we unexpectedly observed that salvicine selectively down-regulated the catalytic subunit of DNA-dependent protein kinase (DNA-PK(CS)) protein levels and repressed DNA-PK kinase activity, both of these effects were attenuated by NAC pretreatment of MCF-7 cells. | |
| Target pathways | NA | |
| IC50 | NA | |
| Potency | Salvicine inhibited the adhesion of human breast cancer MDA-MB-435 cells to fibronectin and collagen without affecting nonspecific adhesion to poly-l-lysine. In this study salvicine induced evident DNA damage, which was further characterized as double-strand breaks mainly in MCF-7 human breast cancer cells. | |
| Cell line/ mice model | MCF-7, MDA-MB-435, MDR K562/A02, K562/A02, KB/VCR and MCF-7/ADR, K562, KB | |
| Additional information | These results indicate that apart from its direct actions, salvicine generates ROS that modulate DNA damage and repair, contributing to the comprehensive biological consequences of salvicine treatment, such as DNA DSBs, apoptosis, and cytotoxicity in tumor cells. The fibronectin-dependent formation of focal adhesions and actin stress fibers was also inhibited by salvicine, leading to a rounded cell morphology. The effect of salvicine on beta(1) integrin function and cell adhesion was reversed by U0126 and SB203580, inhibitors of MAPK/ERK kinase 1/2 and p38 MAPK, respectively. In our study, we show that salvicine effectively kills multidrug-resistant (MDR) sublines, such as K562/A02, KB/VCR and MCF-7/ADR, and parental K562, KB and MCF-7 cell lines to an equivalent degree. These cytotoxic activities of salvicine were much more potent than those of several classical anticancer drugs (average resistance factor: 1.42 for salvicine vs. 344.35, 233.19 and 71.22 for vincristine, doxorubicin and etoposide, respectively). The novel chemical structure of this compound further implies a role for salvicine in future MDR tumor therapy. | |
| PubChem ID | 10359290 | |
| Additional PMIDs | 15592835 16024664 18314480 17723179 12794765 | |
| Additional sources of information | NA | |
| Safety | NA |