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Deoxyelephantopin, a sesquiterpene lactone extracted and purified from Elephantopus scaber, has been shown to exhibit antitumor and hepatoprotective activities. The purpose of this study was to investigate the antiproliferative and apoptosis-inducing properties of deoxyelephantopin in SiHa cells and to elucidate the underlying molecular mechanisms. Deoxyelephantopin inhibited growth of SiHa cells and triggered apoptosis. Apoptosis was accompanied by sequential activation of caspases (8, 9, 3, and 7) and reactive oxygen species (ROS) production. Downregulation of antiapoptotic proteins (Bcl2 and Bcl-xL) and upregulation of apoptotic protein (bax) were also detected. Our results demonstrated that deoxyelephantopin-induced G2/M phase arrest was associated with a marked increase in the levels of p53 and p21 and a decrease in phospho-signal transducer and activator of transcription 3 (pSTAT3-Tyr705), cyclin-dependent kinase 1 (cdc2), and cyclin B1. The expression of p-Akt and p-mTOR was downregulated. p-ERK was inhibited while p-JNK and p-p38 was activated on deoxyelephantopin treatment. Our findings provided the first evidence that STAT3/p53/p21 signaling, MAPK pathway, PI3k/Akt/mTOR pathway, caspase cascades, and ROS play critical roles in deoxyelephantopin-induced G2/M phase arrest and apoptosis of SiHa cells.

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In recent decades, reduced antimicrobial effectiveness, increased bacterial infection, and newly emerged microbial resistance have become global public issues, leading to an urgent need to find effective strategies to counteract these problems. Strategies targeting bacterial virulence factors rather than bacterial survival have attracted increasing interest, since the modulation of virulence factors may prevent the development of drug resistance in bacteria. Spices are promising natural sources of antivirulence compounds owing to their wide availability, diverse antivirulence phytochemical constituents, and generally favorable safety profiles. Essential oils are the predominant and most important antivirulence components of spices. This review addresses the recent efforts of using spice essential oils to inhibit main bacterial virulence traits, including the quorum sensing system, biofilm formation, motility, and toxin production, with an intensive discussion of related mechanisms. We hope that this review can provide a better understanding of the antivirulence properties of spice essential oils, which have the potential to be used as antibiotic alternatives by targeting bacterial virulence. K E Y W O R D Sbiofilm, mechanisms, motility, quorum sensing, spice essential oils, toxin 1018

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