| Properties | Information | |
|---|---|---|
| PhytoCAT-ID | PhytoCAT-163 | |
| Phytochemical name or plant extracts | Silibinin | |
| PMID | 32791535 | |
| Literature evidence | RESULTS: Results indicated significant dose-dependent inhibitory effect of silibinin on proliferation and migration of MDA-MB-231 cells. | |
| IUPAC name | (2R,3R)-3,5,7-trihydroxy-2-[(2R,3R)-3-(4-hydroxy-3-methoxyphenyl)-2-(hydroxymethyl)-2,3-dihydro-1,4-benzodioxin-6-yl]-2,3-dihydrochromen-4-one | |
| Phytochemicals’ class or type of plant extracts | Flavonoid | |
| Source of phytochemicals or plant Extracts | Silybum marianum | |
| Geographical availability | Afghanistan, Albania, Algeria, Azores, Baleares, Baltic States, Belarus, Bulgaria, Canary Is., Central European Rus, Corse, Cyprus, Czechoslovakia, East Aegean Is., East European Russia, Egypt, Ethiopia, France, Germany, Greece, Gulf States, Hungary, India, Iran, Iraq, Italy, Kazakhstan, Kriti, Krym, Kuwait, Lebanon-Syria, Libya, Madeira, Morocco, North Caucasus, North European Russi, Northwest European R, Pakistan, Palestine, Poland, Portugal, Romania, Sardegna, Saudi Arabia, Sicilia, Sinai, South European Russi, Spain, Tadzhikistan, Transcaucasus, Tunisia, Turkey, Turkey-in-Europe, Turkmenistan, Ukraine, Uzbekistan, West Himalaya, Western Sahara, Yemen, Yugoslavia | |
| Plant parts | NA | |
| Other cancers | Breast cancer, Prostate cancer | |
| Target gene or protein | p21, STAT-3, AKT, ERK, EGFR, CD44, MMP2, BRCA1, LRP6, BNIP3, p53, Bak, Bcl-xL, VEGF, MMP9, RAC1, BNIP3 | |
| Gene or Protein evidence | Exposure to silibinin at a concentration of 200 µM inhibited the proliferation of breast cancer (BCa) cells, this concentration also inhibited phosphorylation of STAT3, silibinin inhibits the proliferation and induces apoptosis of MCF-7 cells by down-regulating Bak, P53, P21, BRCA1, BCL-Xl, silibinin induced autophagic cell death through ROS-dependent mitochondrial dysfunction and ATP depletion involving BNIP3 in MCF7 cells. Causes suppression of the Raf/MEK/ERK pathway (MCF-7 breast cancer cells) - inhibition of TPA-induced MMP-9 and VEGF expression Results indicated significant dose-dependent inhibitory effect of silibinin on proliferation and migration of MDA-MB-231 cells. It significantly inhibited the expression of Rac1 mRNA. Silibinin stimulated the expression of Bcl-2 adenovirus E1B 19-kDa-interacting protein 3 (BNIP3), a pro-death Bcl-2 family member, and silencing of BNIP3 greatly inhibited silibinin-induced cell death, decreased ROS production, and sustained ΔΨm and ATP levels. | |
| Target pathways | Blocks the activation of AP-1 via MAPK signaling pathways. Raf/MEK/ERK pathway β1-integrin signaling pathway mTOR and ERK signalling pathways Jak2/STAT3/MMP2 signaling pathway EGFR signaling pathway | |
| IC50 | 100 µM/m against MCF-7 & MDA-MB-231 160 ± 22.2 μM against MCF-7 200 μM against MDA-MB-435/WT 290 μM against MDA-MB-435/DOX 217 μM against MCF-7/WT 572.3 μM against MCF-7/PAC | |
| Potency | In conclusion, the results demonstrate that the silibinin can be used as an experimental therapeutic for the management of TNBC metastatic cancer. | |
| Cell line/ mice model | HEK293, PC-3, DU-145, T-47D, MCF-7, MDA-MB-231, 4T1, MDA-MB-435/WT, MDA-MB-435/DOX, MCF-7/PAC | |
| Additional information | Induces autophagic cell death through ROS-dependent mitochondrial dysfunction and ATP depletion involving BNIP3 in MCF7 cells Represses endogenous LRP6 expression, and blocks Wnt3A-induced LRP6 phosphorylation and Wnt/β-catenin signaling activation (HEK293, PC-3, DU-145, MDA-MB-231 and T-47D) Increases the level of P21 (MDA-MB-231) Supresses PMA-induced MMP-9 expression in MCF-7 Inhibits telomerase expression in T47D human breast cancer cells Reduces DOX IC50 from 71 to 10 μg/mL (in DOX-resistant MDA-MB-231 cells) Blocks mammalian target of rapamycin signaling with a concomitant reduction in translation initiation (in MCF-7 cells) Inhibits the expression of Cdc42 and D4-GDI mRNAs Downregulation of ERα expression downstream resulting in induction of autophagy and apoptosis (MCF-7) Down-regulation of Bak, P53, P21, BRCA1, BCL-Xl (MCF-7) Causes downregulation of miR-21 and miR-155, and the upregulation of their apoptotic targets - CASP-9, BID, APAF-1, CASP-3, CASP-8, and PDCD4, upregulation of CASP-9 and BID (MCF-7) In combination with paclitaxel or cisplatin, silibinin causes significant decrease in anti-apoptotic Bcl-2 with increase in pro-apoptotic Bax, P53, BRCA1 and ATM mRNA levels Increases p53 expression (MCF-7) Silibinin, a flavonoid antioxidant from milk thistle (Silybum marianum L.), has attracted attention in the last decades for chemoprevention and chemotherapy of tumor cells. In combination with etoposide, it increases the expression of P53, P-P53, and P21 in MCF-7 cells, and individually increase p21 Inhibits phosphorylation of STAT3 and its principal upstream kinase, Jak2, inhibits nuclear translocation of STAT3, as well as its binding to the MMP2 gene promoter Reduces the EGFR ligand-induced CD44 and matrix metalloproteinase-9 (MMP-9) expression, suppresses the EGF-induced phosphorylation of EGFR and extracellular signal-regulated kinase1/2 (ERK1/2) Inhibits the expression of Rac1 mRNA (MDA-MB-231 cells) CAM assay results suggested that AND, Silbinin (SIL) and TA increase the anti-angiogenic potential of PTX. Thus, natural compounds can be used to improve the anti-cancer potential of PTX. | |
| PubChem ID | 31553 | |
| Additional PMIDs | 22110198 25891311 22820499 27402681 35083008 17214970 19181503 23886126 28027688 32791535 19509268 21166494 22101790 26117209 25773855 27066095 28440514 29515635 28843263 21847388 35083008 28027688 32473632 32791535 34000264 | |
| Additional sources of information | https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:249211-1 | |
| Safety | NA |