Eriocalyxin B (EriB), a natural ent-kaurane diterpenoid isolated from Isodon eriocalyx var. laxiflora, has been reported to exhibit anti-tumor and anti-inflammatory activities. The mechanisms of action of its anti-angiogenic and anti-tumor activities were further elucidated by our research team using various in vitro and in vivo models. The anti-angiogenic activities of EriB were investigated in human endothelial cells, zebrafish and mouse models, while the anti-tumor effects were evaluated in both estrogen receptor (ER)-positive and ER-negative human breast cancer cells as well as breast xenograft mouse models. Results showed that EriB at 50 or 100 nM could significantly suppress vascular endothelial growth factors (VEGF)-induced cell proliferation, tube formation and cell migration in human endothelial cells, which involved down-regulation of VEGFR-2 signaling pathway [1]. The inhibitory activity on angiogenesis were also observed in zebrafish embryos and mouse matrigel plug models. While in human breast cancer cells, EriB at 1.5 or 2.25 mM induced apoptosis and triggered autophagy by inhibition of Akt/mTOR/p70S6K signaling pathway, as well as coordinated the crosstalk between apoptosis and autophagy [2]. Furthermore, EriB treatment (10 mg/kg) could induce autophagy and anti-angiogenic effects in breast xenograft-bearing mice. Our recent comprehensive transcriptome analysis in zebrafish embryos illustrated that EriB at 10 or 15 mM could enrich several pathways, such as glutathione metabolism, phototransduction, and metabolism of xenobiotics by cytochrome P450 [3]. The target genes involved in the regulation of signaling pathways by EriB were newly identified, which will provide new insight of the biological activities of this natural compound. In conclusion, the multi-targeted activities of EriB were further verified through the molecular studies and functional tests in cell-based and animal models. The great potential of this compound to be developed as an anti-cancer agent for breast cancer is warranted.
References:
[1] Zhou et al., Oncotarget. 2016;7(50):82820-82835.
[2] Zhou et al., Biochem Pharmacol. 2017;142:58-70.
[3] Zhou et al., Mol Omics. 2018;14(3):156-169.