Triple-negative breast cancer (TNBC) accounts for 15% of overall breast cancer. A lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2 receptor) makes TNBC more aggressive and metastatic. Wnt signaling is one of the important pathways in the cellular process; in TNBC it is aberrantly regulated, which leads to the progression and metastasis. In this study, we designed a therapeutic strategy using a combination of a low dose of paclitaxel and a Wnt signaling inhibitor (XAV939), and examined the effect of the paclitaxel-combined XAV939 treatment on diverse breast cancer lines including TNBC cell lines (MDA-MB-231, MDA-MB-468, and BT549) and ER+ve cell lines (MCF-7 and T-47D). The combination treatment of paclitaxel (20 nM) and XAV939 (10 µM) exerted a comparable therapeutic effect on MDA-MB-231, MDA-MB-468, BT549, MCF-7, and T-47D cell lines, relative to paclitaxel with a high dose (200 nM). The paclitaxel-combined XAV939 treatment induced apoptosis by suppressing Bcl-2 and by increasing the cleavage of caspases-3 and PARP. In addition, the in vivo results of the paclitaxel-combined XAV939 treatment in a mice model with the MDA-MB-231 xenograft further confirmed its therapeutic effect. Furthermore, the paclitaxel-combined XAV939 treatment reduced the expression of β-catenin, a key molecule in the Wnt pathway, which led to suppression of the expression of epithelial-mesenchymal transition (EMT) markers and angiogenic proteins both at mRNA and protein levels. The expression level of E-cadherin was raised, which potentially indicates the inhibition of EMT. Importantly, the breast tumor induced by pristane was significantly reduced by the paclitaxel-combined XAV939 treatment. Overall, the paclitaxel-combined XAV939 regimen was found to induce apoptosis and to inhibit Wnt signaling, resulting in the suppression of EMT and angiogenesis. For the first time, we report that our combination approach using a low dose of paclitaxel and XAV939 could be conducive to treating TNBC and an external carcinogen-induced breast cancer.

Psoriasis is a recurrent skin disease described as keratinocyte hyperproliferation and aberrant differentiation. Erianin, a bibenzyl compound extracted from Dendrobium chrysotoxum, has displayed antitumor and anti-angiogenesis effects. However, the effects of erianin on a human keratinocyte cell line (HaCaT) are not fully understood. In the present study, we explored the effect of erianin on proliferation and apoptosis in HaCaT cells. Our results indicated that treatment with erianin ranging from 12.5 nM to 50 nM inhibited proliferation and induced apoptosis of HaCaT cells. In addition, erianin-induced apoptosis was accompanied by elevated reactive oxygen species (ROS). The ROS scavenger N-acetyl-cysteine (NAC) attenuated this elevation. Moreover, treatment with erianin induced activation of the c-Jun N-terminal kinase (JNK)/c-Jun signaling pathway and suppressed the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, while pretreatment with NAC also reversed these effects. Collectively, these data demonstrated that erianin inhibited proliferation and induced apoptosis of HaCaT cells through ROS-mediated JNK/c-Jun and AKT/mTOR signaling pathways. Erianin could be recognized as a potential anti-psoriasis drug.