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Over the last decade, researchers have paid more and more attention to the natural compound curcumin for its potential application in anticancer therapy. However, the application of curcumin has been limited owing to its rapid metabolism in the body. HO-3867, a stable curcumin analog, shows potent antitumor activities against various tumor cells. Yet, information on HO-3867's impact on non-small-cell lung cancer (NSCLC) cells is lacking. Herein, we evaluated the cytotoxicity of HO-3867 in NSCLC cells. We discovered that HO-3867 suppressed the viability of NSCLC cells containing wild-type p53. In NSCLC cells, HO-3867 promotes both apoptosis and ferroptosis, the latter of which is a newly discovered mode of cell death. Mechanically, HO-3867-induced apoptosis relied on the inhibition of Mcl-1 and Bcl-2 and the upregulation of Bax. Moreover, NSCLC cells undergo ferroptosis when treated with HO-3867 via activating the p53-DMT1 axis and suppressing GPX4. Additionally, HO-3867 caused an accumulation of reactive oxygen species (ROS) in NSCLC in a way that was dependent on the presence of iron. Our findings point to the possibility that HO-3867 might be employed as a therapeutic agent for treating NSCLC. [ABSTRACT FROM AUTHOR]

Objective. To investigate the absorption property of the representative hydrolyzable tannin, namely corilagin, and its hydrolysates gallic acid (GA) and ellagic acid (EA) from the Fructus Phyllanthi tannin fraction (PTF) in vitro. Methods. Caco-2 cells monolayer model was established. Influences of PTF on Caco-2 cells viability were detected with MTT assay. The transport across monolayers was examined for different time points, concentrations, and secretory directions. The inhibitors of P-glycoprotein (P-gp), multidrug resistance proteins (MRPs), organic anion transporting polypeptide (OATP) and sodium/glucose cotransporter 1 (SGLT1), and tight junction modulators were used to study the transport mechanism. LC-MS method was employed to quantify the absorption concentration. Results. The apparent permeability coefficient (Papp) values of the three compounds were below 1.0 × 10−6 cm/s. The absorption of corilagin and GA were much lower than their efflux, and the uptake of both compounds was increased in the presence of inhibitors of P-gp and MRPs. The absorption of EA was decreased in the company of OATP and SGLT1 inhibitors. Moreover, the transport of corilagin, GA, and EA was enhanced by tight junction modulators. Conclusion. These observations indicated that the three compounds in PTF were transported via passive diffusion combined with protein mediated transport. P-gp and MRPs might get involved in the transport of corilagin and GA. The absorption of EA could be attributed to OATP and SGLT1 protein. [ABSTRACT FROM AUTHOR]