Three new oxygenated yohimbane-type alkaloids from Ophiorrhiza japonica.

A series of oxygenated yohimbane alkaloids, including three new compounds, ophiorrhines H-J (1-3), and seven known compounds, were isolated from the aerial parts of Ophiorrhiza japonica. The structures with absolute configurations were elucidated by extensive MS and NMR spectroscopic methods, as well as the single crystal X-ray diffraction and ECD calculations. Ophiorrhines H (1) and I (2) represent key oxygenated intermediates in the formation of aromatic ring E in the demethoxycarbonyl-3,14-dihydrogambirtannine (10). Ophiorrhine J (3) is a highly oxidized yohimbane derivative with the planar superconjugated system. The cytotoxic activities of all alkaloids against five human cancer cell lines were evaluated.

Corrigendum: ß-Sitosterol and Gemcitabine Exhibit Synergistic Anti-Pancreatic Cancer Activity by Modulating Apoptosis and Inhibiting Epithelial-Mesenchymal Transition by Deactivating Akt/GSK-3ß Signaling.

[This corrects the article DOI: 10.3389/fphar.2018.01525.].

ß-Sitosterol and Gemcitabine Exhibit Synergistic Anti-pancreatic Cancer Activity by Modulating Apoptosis and Inhibiting Epithelial-Mesenchymal Transition by Deactivating Akt/GSK-3ß Signaling.

ß-sitosterol (BS), a major bioactive constituent present in plants, has shown potent anti-cancer activity against many human cancer cells, but its activity in pancreatic cancer (PC) cells has rarely been reported. Gemcitabine (GEM) is one of the first-line drugs for PC therapy, however, the treatment effect is not sustained due to prolonged drug resistance. In this study, we firstly studied the anti-PC activity and the mechanism of BS alone and in combination with GEM in vitro and in vivo. BS effectively inhibited the growth of PC cell lines by inhibiting proliferation, inducing G0/G1 phase arrest and apoptosis, suppressed the NF- kB activity, and increased expression of the protein Bax but decreased expression of the protein Bcl-2. Moreover, BS inhibited migration and invasion and downregulated epithelial-mesenchymal transition (EMT) markers and AKT/GSK-3ß signaling pathways. Furthermore, the combination of BS and GEM exhibited a significant synergistic effect in MIAPaCa-2 and BXPC-3 cells. More importantly, the combined treatment with BS and GEM lead to significant growth inhibition of PC xenografts. Overall, our data revealed a promising treatment option for PC by the combination therapy of BS and GEM.