Cancer: Breast, gastric, Leydig cell, gall bladder
Action: Potentiates chemotherapy, restores T cell function, MDR, induces apoptosis
Estrogen Agonist
Icariin is a pure extract of the traditional Chinese medicine Herba epimedii. It is a flavonoid found in several species of the genus Epimedium (L.).
The estrogenic activities of icariin (ICA) and its derivatives were investigated, and their structure-estrogenic activity relationship determined. Icaritin (ICT) and desmethylicaritin (DICT) were derived from ICA. The estrogenic activities of ICA, ICT and DICT were examined by cell proliferation and progestogen receptor mRNA expression of estrogen-receptor-positive MCF-7 cells.
These studies indicated that ICT and DICT both markedly enhanced the proliferation of MCF-7 cells; as compared to estradiol (100%); their relative proliferative effects (RPE) were 90% and 94%, respectively. Those phenomena were not observed with ICA. Results demonstrate that ICT and DICT (nonconjugated forms) possess estrogen-like activity; however, ICA appears to have no estrogenicity in the MCF-7 cell line model in vitro (Ye et al., 2005).
Gastric Cancer
In an in vitro study, the inhibitory effect and underlying molecular mechanism of icariin was investigated on the invasive and migration properties of human gastric cancer cell line BGC-823. At 50% growth-inhibiting concentration, icariin significantly suppressed tumor cells migration and invasion, which were traceable to down-regulation of Rac1 and VASP.
Together with icariin, the selected siRNA targeting Rac1 or VASP reinforced these inhibitory effects. Moreover, transfection with Rac1 plasmids pcDNA3-EGFP-Rac1-Q61L led to the enhancement in expression level of both Rac1 and VASP.
These results indicate that icariin exerts negative effects on tumor cell invasion and migration via the Rac1-dependent VASP pathway and may be a potential anti-cancer drug (Wang et al., 2010).
Gallbladder Cancer; Gemcitabine
Icariin, by suppressing NF-κB activity, exerts anti-tumor activity, and potentiates the anti-tumor activity of gemcitabine in gallbladder cancer. Combined administration of gemcitabine and icariin may offer a better therapeutic option for patients with gallbladder cancer. Icariin (40-160 µg/mL) dose-dependently suppressed cell proliferation and induced apoptosis in both GBC-SD and SGC-996 cells, with SGC-996 cells being less sensitive to the drug. Icariin (40 µg/mL) significantly enhanced the anti-tumor activity of gemcitabine (0.5 µmol/L) in both GBC-SD and SGC-996 cells (Zhang et al., 2013).
Restores T cell function
Tumor-induced myeloid-derived suppressor cells (MDSCs) are a critical barrier to effective immunotherapy of cancer. We identified that Docetaxel and a natural compound, Icariin, can target MDSCs with preferential apoptosis of M2 cells and polarization of the surviving cells towards M1 cells. Such strategic targeting of MDSCs restored T cell function accompanied by tumor retardation in vivo (Djeu & Wei, 2012).
Leydig Cell (Testicle)
Findings suggest a novel anti-cancer effect of icariin in Leydig cell tumor, derived from interstitial cells (rare neoplasm) through activation of the mitochondrial pathway and down-regulation of the expression of piwil4 (Wang et al., 2011).
Induces Apoptosis
Icariin triggered the mitochondrial/caspase apoptotic pathway indicated by enhanced Bax-to-Bcl-2 ratio, loss of mitochondrial membrane potential., cytochrome c release, and caspase cascade. Moreover, icariin induced a sustained activation of the phosphorylation of c-Jun N-terminal kinase (JNK) but not p38 and ERK1/2, and SP600125 (an inhibitor of JNK) almost reversed icariin-induced apoptosis in SMMC-7721 cells. In addition, icariin provoked the generation of reactive oxygen species (ROS) in SMMC-7721 cells, while the anti-oxidant N-acetyl cysteine almost completely blocked icariin-induced JNK activation and apoptosis. Taken together, these findings suggest that icariin induces apoptosis through a ROS/JNK-dependent mitochondrial pathway (Li et al., 2010).
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