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Lilii Bulbus is a folk medicine for both culinary and medicinal purpose. In traditional medicine theory, Lilii Bulbus is usually used as an complementary therapy for nourishing the heart and lung, clearing heat in the treatment of mental instability and depression. In this study, NLPS-1a (Mw = 2610 Da, DP = 16), a water-soluble non-starch Lilii Bulbus polysaccharides, was isolated and purified. Structural analysis showed that NLPS-1a mainly contained Man and Glc with a molar ratio of 11.137 and 9.427. The glycosidic linkages of NLPS-1a were 1,3-Manp (59.93%), 1,2-Glcp (37.93%), T-Glcp (1.21%) and T-Manp (0.93%), indicating the highly-linear structures. In addition, NLPS-1a could significantly repair the injury of PC12 cells induced by corticosterone (CORT), reduce Lactate dehydrogenase (LDH) leakage and decrease the cell apoptosis in a dose-dependent manner. Above all, the results indicated that NLPS-1a had protective effects against CORT-induced neurotoxicity in PC12 cells, and might be a natural antidepressant, which enriched the study of the metabolic mechanism between herbal polysaccharides and antidepressant., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Heat shock protein 90 (Hsp90) serves as an ATP-dependent molecular chaperone for numerous cell signaling proteins, including many oncogenes and clinically validated cancer targets that are involved in cell proliferation and survival. Recent studies have shown that the Hsp90 inhibitor, SNX-2112, effectively inhibits tumor cell growth and angiogenesis in hematological and solid tumors. However, little is known about the effects of SNX-2112 on leukemias that are resistant to chemotherapy, which is emerging as a major clinical problem. In this study, the effects of SNX-2112 on the multidrug-resistant human chronic myeloid leukemia (CML) K562/ADR cell line were investigated. We observed that SNX-2112 exhibited dose- and time-dependent inhibitory activities against K562/ADR cells. These effects included the induction of apoptosis and secondary necrosis in addition to cell cycle arrest at the G1 and G2 phases. Furthermore, SNX-2112-induced apoptosis was predominantly mediated by the mitochondrial pathway, initiated by the release of cytochrome c and the participation of Bcl-2 family proteins. SNX-2112 also induced the activation of the caspase-3, -8 and -9 cascade and the subsequent cleavage of PARP in K562/ADR cells. Moreover, the inactivation of the Akt and NF-κB signaling pathways may be involved in SNX-2112-induced apoptosis. The expression levels of P-glycoprotein (P-gp) and several chaperons related to drug resistance and apoptosis were also shown to be inhibited, including the Grp78 and Hsp90 isoforms, Grp94 and Trap1. Taken together, these results provide a possible molecular mechanism for the anti-cancer effect of SNX-2112 on K562/ADR cells and provide new insights into the future application of SNX-2112 as a therapeutic agent for anti-multidrug-resistant leukemias., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

A new zwitterionic monolayer film of sulfobetaine was constructed by grafting novelly designed N,N-dimethyl (beta-hydroxyethyloxyethyl) ammonium propanesulfonate (DHAPS) to hydroxyl groups of glass in the presence of hexamethylene diisocyanate (HDI) as a coupling agent and dibutyltin dilaurate (DBTDL) as a catalyst. Experiments of blood adhesion proved that the zwitterionic film possessed excellent hydrophilicity and very good biocompatibility and provided an appropriate biomimetic interface for adhesion and proliferation of cells. Thus, the monitoring of the cell proliferation and apoptotic processes on the zwitterionic surface during an incubation process was achieved, using different techniques, such as electrochemical impedance spectroscopy, scanning electron microscopy, flow cytometric assay, and Trypan blue staining. K562 leukemia cells, as a model, cultured in vitro on the zwitterionic surface kept their viability for 5 days and remained healthy and undifferentiated, indicating that the zwitterionic surface did not have a deleterious effect on cell growth in normal conditions. Thus, this man-made interface would be applicable to the growth of cells and the study of biomaterial-cell interaction and has potential applications in medicine and cytobiology.

Triple-negative breast cancer (TNBC) is a malignant tumor without specific therapeutic targets and a poor prognosis. Chemotherapy is currently the first-line therapeutic option for TNBC. However, due to the heterogeneity of TNBC, not all of TNBC patients are responsive to chemotherapeutic agents. Therefore, the demand for new targeted agents is critical. β -tubulin isotype III (Tubb3) is a prognostic factor associated with cancer progression, including breast cancer, and targeting Tubb3 may lead to improve TNBC disease control. Shikonin, the active compound in the roots of Lithospermun erythrorhizon suppresses the growth of various types of tumors, and its efficacy can be improved by altering its chemical structure. In this work, the anti-TNBC effect of a shikonin derivative (PMMB276) was investigated, and its mechanism was also investigated. This study combines flow cytometry, immunofluorescence staining, immunoblotting, immunoprecipitation, siRNA silencing, and the iTRAQ proteomics assay to analyze the inhibition potential of PMMB276 on TNBC. In vivo study was performed, Balb/c female murine models with or without the small molecule treatments. Herein, we screened 300 in-house synthesized analogs of shikonin against TNBC and identified a novel small molecule, PMMB276; it suppressed cell proliferation, induced apoptosis, and arrested the cell cycle at the G2/M phase, suggesting that it could have a tumor suppressive role in TNBC. Tubb3 was identified as the target of PMMB276 using proteomic and biological activity analyses. Meanwhile, PMMB276 regulated microtubule dynamics in vitro by inducing microtubule depolymerization and it could act as a tubulin stabilizer by a different process than that of paclitaxel. Moreover, suppressing or inhibiting Tubb3 with PMMB276 reduced the growth of breast cancer in an experimental mouse model, indicating that Tubb3 plays a significant role in TNBC progression. The findings support the therapeutic potential of PMMB276, a Tubb3 inhibitor, as a treatment for TNBC. Our findings might serve as a foundation for the utilization of shikonin and its derivatives in the development of anti-TNBC. A small novel molecule, i.e., α-lipoic acyl shikonin, modified form of a natural product (shikonin), acts as a novel inhibitor of Tubb3. [Display omitted] [ABSTRACT FROM AUTHOR]

Four novel oxidovanadium( IV) complexes, [ VO(hntdtsc)( PHIP)] ( 1) (hntdtsc = 2-hydroxy-1-naphthaldehyde thiosemicarbazone, PHIP= 2-phenyl-imidazo[4,5-f]1,10-phenanthroline), [ VO(hntdtsc)( DPPZ)]( 2)( DPPZ= dipyrido[3,2-a:2',3'-c]phenazine), [ VO(satsc)( PHIP)]( 3) (satsc=salicylaldehyde thiosemicarbazone), and [ VO(satsc)( DPPZ)]( 4), have been prepared and characterized. The chemical nuclease activities and photocleavage reactions of the complexes were tested. All four complexes can efficiently cleave pBR322 DNA, and complex 1 has the best cleaving ability. The antitumor properties of these complexes were examined with three different tumor cell lines using MTT assay. Their antitumor mechanism has been analyzed using cell cycle analysis, fluorescence microscopy of apoptosis, and Annexin V- FITC/ PI assay. The results showed that the growth of human neuroblastoma ( SH- SY5Y, SK-N- SH) and human breast adenocarcinoma ( MCF-7) cells were inhibited significantly with very low IC50 values. Complex 1 was found to be the most potent antitumor agent among the four complexes. It can cause G0/G1 phase arrest of the cell cycle and exhibited significant induced apoptosis in SK-N- SH cells and displayed typical morphological apoptotic characteristics. In addition, they all displayed reasonable abilities to scavenge hydroxyl radical, and complex 1 was the best inhibitor. [ABSTRACT FROM AUTHOR]

Three oxovanadium complexes incorporating thiosemicarbazones and fluoro-phenanthroline derivatives [VO(hntdtsc)(CF 3 PIP)] ( 1 ) (hntdtsc = 2-hydroxyl-1-naphthaldehyde thiosemicarbazone, CF 3 PIP = 2-(2-trifluoromethyl phenyl)imidazole[4,5-f][1,10]phenanthroline [VO(hntdtsc)( m -CF 3 PIP)] ( 2 ) ( m -CF 3 PIP = 2-(3-trifluoromethyl phenyl)imidazole[4,5-f][1,10]phenanthroline), [VO(hntdtsc)( p -CF 3 PIP)] ( 3 ) ( p -CF 3 PIP = 2-(4-trifluoromethyl phenyl)imidazole[4,5-f][1,10]phenanthroline) were newly synthesized and characterized by elemental analysis and spectroscopic techniques. Their interactions with calf-thymus DNA (CT-DNA) and photocleavage properties with plasmid pBR322 DNA were investigated by a host of analytical methods. The results suggest that these three complexes interact with CT-DNA through an non-classical intercalative mode and can efficiently cleavage plasmid pBR322 DNA upon exposure to ultraviolet light. In addition, they all exhibited considerable anti-proliferative activity in vitro against human Hela, CaSki, SiHa, ECa9706, ECa109, MDA-MB-231 and MCF-7 tumor cell lines, to have an IC 50 values for cytotoxicity in the low micromole range 0.31–6.15 μM, which is very close to that of cisplatin (0.52–2.49 μM). Furthermore, their antitumor mechanism has been analyzed by the cell cycle arrest, and apoptosis analysis. The results showed that complexes 2 and 3 caused G0/G1 phase arrest in ECa9706 cells, but differentiatedly induced G0/G1 and S phase arrest in ECa109 cells. And significant apoptosis were observed in both the two tumor cell lines, which indicate these oxovanadium complexes induce proliferative suppression of ECa9706 and ECa109 cells via the induction of apoptosis. [ABSTRACT FROM AUTHOR]

Abstract: In this study, BODIPY-appended calix[4]arene was chosen as a fluorescent probe for intracellular pH. The compound with cell permeability can monitor the minor pH change near neutrality inside the cell and is the first BODIPY-derived probe reported for cytosolic pH. Owing to a high level of cell retention and minor cytotoxicity of the probe, stable fluorescence is provided in the cells for 24h, facilitating the precise observation of intracellular pH. A model of cell apoptosis was designed by exposure of the cells to a low concentration of hydrogen peroxide. An increase in the fluorescence of the cells confirmed that BODIPY-appended calix[4]arene sensed the fluctuation of the cellular pH during early cell apoptosis. The developed fluorescent pH probe will be useful for the study of cell apoptosis. [Copyright &y& Elsevier]