| Properties | Information | |
|---|---|---|
| PhytoCAT-ID | PhytoCAT-515 | |
| Phytochemical name or plant extracts | Matrine | |
| PMID | 24554536 | |
| Literature evidence | Overall, we conclude that matrine could induce apoptosis of human NPC cells via VEGF-A/ERK1/2 pathway, which supports the potential use of matrine in clinically treating NPC. © Georg Thieme Verlag KG Stuttgart · New York. | |
| IUPAC name | (1R,2R,9S,17S)-7,13-diazatetracyclo[7.7.1.02,7.013,17]heptadecan-6-one | |
| Phytochemicals’ class or type of plant extracts | Alkaloid | |
| Source of phytochemicals or plant Extracts | Sophora flavescens | |
| Geographical availability | Altay, Amur, China North-Central, China South-Central, China Southeast, Chita, Hainan, Inner Mongolia, Irkutsk, Japan, Khabarovsk, Korea, Manchuria, Mongolia, Primorye, Qinghai, Taiwan, Tibet, Xinjiang | |
| Plant parts | NA | |
| Other cancers | Breast cancer | |
| Target gene or protein | PTEN, miR-21 , AKT, Bad, p21(/WAF1/CIP1), p27(/KIP1), Bcl-2, Bax, VEGF, VEGFR-2, Caspase 3, Caspase 9, P-gp, MRP1, IKKβ, GRP78, eIF2α, CHOP, p62, mTOR, Topo I, LIN28A/Let-7 | |
| Gene or Protein evidence | Matrine up-regulated PTEN by downregulating miR-21 which in turn dephosphorylated Akt, resulting in accumulation of Bad, p21(/WAF1/CIP1) and p27(/KIP1). Western blot analysis of tumoral homogenates indicated that matrine therapy reduced the ratio of Bcl-2/Bax, downregulated the expressions of VEGF and VEGFR-2, and increased the activation of caspase-3 and caspase-9. Compared with control group, 0.6, 1.2 mg/mL Matrine reduced protein expressions of P-gp, MRP1, p-AKT, Bcl-2, but increased PTEN, Bax, and cleaved caspase-3 gradually, and unchanged caspase-3. The experimental results also suggested that the antitumor effects of matrine on breast cancer cells may be associated with the downregulation of IKKβ expression by matrine, as indicated by the western blot analysis results. Mechanistic investigations revealed that matrine treatment causes ER dilation and up-regulated the expression of ER stress markers GRP78, eIF2α, and CHOP, increases the levels of apoptotic in Michigan Cancer Foundation cells, subsequently, blocking the ER stress-mediated apoptosis pathway, significantly decreased matrine-induced apoptotic but still has significant difference between control group. Furthermore, matrine induced autophagy in MCF‑7 cells, manifesting as an accumulation of light chain 3 II and downregulation of p62. Additionally, matrine suppressed AKT and mammalian target of rapamycin (mTOR) phosphorylation, indicating that the AKT/mTOR pathway is involved in matrine‑induced apoptosis and autophagy. Our study uncovers the role of the LIN28A/Let-7 in BrCSCs renewal, and more importantly, elucidated a novel mechanism by which Matrine induces breast cancer involution. | |
| Target pathways | NF-κB signaling pathway miR-21/PTEN/Akt pathway PI3K/AKT signaling pathway LIN28A/Let-7 pathway ER stress-mediated apoptosis pathway AKT/mTOR pathway | |
| IC50 | 9.40 ± 1.12 mM against MDA-MB-468 | |
| Potency | Matrine inhibited MCF-7 cell growth in a concentration-and time-dependent manner, by inducing apoptosis and cell cycle arrest at G(1)/S phase. Administration of matrine inhibited the growth of primary tumors and their metastases to lungs and livers, in a dose-dependent manner, in a highly metastatic model of 4T1 breast cancer established in syngeneic Balb/c mice. This study suggests matrine may be a potent agent, from a natural resource, for treating metastatic breast cancer because of its anti-apoptotic, anti-proliferative and anti-angiogenic activities. | |
| Cell line/ mice model | MCF-7, 4T1 Balb/c mice, MCF-7/ADR, MDA-MB-231, BT-474, MDA-MB-468 | |
| Additional information | Matrine inhibited MCF-7/ADR cell growth, induced apoptosis, and reversed multidrug resistance for breast cancer cells through the regulation of downstream apoptosis factors of PI3K/AKT signaling pathway by decreasing cell phosphorylation of AKT level. Matrine suppression of self-renewal was dependent on regulation of LIN28A/Let-7 pathway in breast cancer stem cells | |
| PubChem ID | 91466 | |
| Additional PMIDs | 31615459 21061465 24554536 29130495 31595560 22832383 24137358 28185329 33000249 34080963 29434864 | |
| Additional sources of information | https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:518831-1 | |
| Safety | NA |