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Genistein is one of the main components of soy-based foods, which are widely known for their many benefits, including anti-cancer, anti-inflammatory, and antioxidant effects. In this study, we investigated the anti-metastasis effects of genistein on B16F10 melanoma cells. Our results showed that genistein strongly inhibited B16F10 cell proliferation and induced apoptosis in time- and concentration-dependent manners. Genistein altered the morphology of B16F10 cells to an elongated shape with slim pseudopodia-like protrusions. Moreover, genistein inhibited the invasion and migration abilities of B16F10 cells in a dose-dependent manner. On one hand, a high concentration of genistein (100 μM) significantly inhibited cell adhesion and migration, as shown by wound healing assays and transwell-migration and invasion assays. Furthermore, the expression levels of p-FAK, p-paxillin, tensin-2, vinculin, and α-actinin were decreased by genistein. As a result, genistein is believed to strongly downregulate the migration and invasion abilities of B16F10 cells via the FAK/paxillin pathway. Moreover, p-p38, p-ERK, and p-JNK levels were also dramatically decreased by treatment with genistein. Finally, genistein significantly decreased the gene expression of FAK, paxillin, vimentin, and epithelial-to-mesenchymal transition-related transcription factor Snail, as shown by real-time PCR (qPCR) analysis. On the other hand, a lower concentration of genistein (12.5 μM) significantly promoted both invasion and migration by activating the FAK/paxillin and MAPK signaling cascades. Taken together, this study showed for the first time that genistein exerts dual functional effects on melanoma cells. Our findings suggest that genistein regulates the FAK/paxillin and MAPK signaling pathways in a highly concentration-dependent manner. Patients with melanoma should therefore be cautious of consuming soy-based foods in their diets.

Nanoparticle drug delivery carriers, which can implement high performances of multi-functions, are of great interest, especially for improving cancer therapy. Herein, we reported a new approach to construct Mn 2+ -coordinated doxorubicin (DOX)-loaded poly(lactic- co -glycolic acid) (PLGA) nanoparticles as a platform for synergistic chemo-photothermal tumor therapy. DOX-loaded PLGA (DOX/PLGA) nanoparticles were first synthesized through a double emulsion-solvent evaporation method, and then modified with polydopamine (PDA) through self-polymerization of dopamine, leading to the formation of PDA@DOX/PLGA nanoparticles. Mn 2+ ions were then coordinated on the surfaces of PDA@DOX/PLGA to obtain Mn 2+ -PDA@DOX/PLGA nanoparticles. In our system, Mn 2+ -PDA@DOX/PLGA nanoparticles could destroy tumors in a mouse model directly, by thermal energy deposition, and could also simulate the chemotherapy by thermal-responsive delivery of DOX to enhance tumor therapy. Furthermore, the coordination of Mn 2+ could afford the high magnetic resonance (MR) imaging capability with sensitivity to temperature and pH. The results demonstrated that Mn 2+ -PDA@ DOX/PLGA nanoparticles had a great potential as a smart theranostic agent due to their imaging and tumor-growth-inhibition properties.

An unusual katsumadain dimer via a [2 + 2] cycloaddition, katsumadain C (1), and a unique chalcone-diarylheptanoid adduct via a Diels-Alder reaction, calyxin Y (2) with novel carbon frameworks, were isolated from the seeds of Alpinia katsumadai. Their structures and relative configurations were determined by spectroscopic evidence.

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