Introduction Glioblastoma multiforme (GBM) is the most aggressive malignant primary brain tumor, characterized by poor prognosis. Moreover, cognitive impairment from the tumor and its treatments compromises patients' quality of life. Butyrylcholinesterase (BChE) inhibition enhances cognitive function. Notably, BCHE is overexpressed in GBM tissues; its downregulation suppresses tumor cell proliferation, migration, and invasion. This study aimed to identify a BChE inhibitor with dual functionality: anti-GBM efficacy and cognitive protection via modulation of neuroinflammation.Methods QY-69 was identified from an in-house BChE inhibitor library through cytotoxicity-based screening. Its anti-GBM effects were evaluated through colony formation, wound healing, and transwell assays. Orthotopic GBM mice were treated with QY-69 orally for 15 days. Tumor progression, cognitive function (Morris water maze), and neuroinflammation (microglia and astrocyte immunofluorescence) were analyzed.Results QY-69 exhibited significant antiproliferative activity at micromolar concentrations. In vitro assays demonstrated significant inhibition of GBM cell growth, migration, and invasion. Behavioral impairment in mice was improved, and the activation of astrocytes and microglia in peritumoral tissues was reduced, indicating a decrease in neuroinflammation.Discussion QY-69 demonstrated dual therapeutic potential in GBM by inhibiting tumor progression and alleviating cognitive impairment. However, its precise molecular mechanisms remain to be elucidated. Future research should employ transcriptomic and proteomic approaches to elucidate the molecular basis of its anti-GBM activity.Conclusion QY-69, a BChE inhibitor, exhibits potent anti-GBM activity and confers cognitive protection, positioning it as a promising dual-action therapeutic candidate. By inhibiting tumor progression and reducing neuroinflammation, it may enhance both survival and quality of life in GBM patients.

OBJECTIVE:This study aims to investigate whether butyrylcholinesterase (BChE) inhibitor QY-54 can be used to treat glioblastoma (GBM) and exert a neuroprotective profile. METHODS:At the cellular level, the effects of QY-54 on the proliferation, invasion, and migration of GBM cells from different species were investigated. At the animal level, the safety of QY-54 in normal mice, its anti-tumor effects in GBM mice, and its effects on cognition protective function were examined. RESULTS:At the cellular level, QY-54 exhibited significant inhibitory effects on the proliferation, migration, and invasion of GBM cells derived from different species. At the animal level, QY-54 showed low toxicity in normal mice. Moreover, it significantly inhibited GBM tumor growth, promoted tumor cell apoptosis, suppressed neuroinflammation, protected neurons, and improved the general condition and cognitive function of GBM mice. In Western blot experiments, QY-54 upregulated c-jun N-terminal kinase (JNK) levels to exert an inhibitory effect on glioma. CONCLUSION:QY-54 exhibits dual effects of anti-glioblastoma and cognitive improvement, by inhibiting BChE and activating the JNK signaling pathway. QY-54 is a highly promising drug for the treatment of glioblastoma with neuroprotective profile.

Aim: Physcion, an anthraquinone derivative, exhibits hepatoprotective, anti-inflammatory, anti-microbial and anti-cancer activities. In this study we examined whether and how physcion inhibited metastatic potential of human colorectal cancer cells in vitro . Methods: Human colorectal cancer cell line SW620 was tested. Cell migration and invasion were assessed using a wound healing and Transwell assay, respectively. The expression levels of transcription factor SOX2 in the cells were modulated with shRNA targeting SOX2 and SOX2 overexpressing plasmid. The expression of target molecules involved in epithelial-mesenchymal transition (EMT) process and the signaling pathways was determined with Western blots or qRT-PCR. ROS levels were measured using DCF-DA. Results: Physcion (2.5, 5 mol/L) did not affect the cell viability, but dose-dependently inhibited the cell adhesion, migration and invasion. Physcion also inhibited the EMT process in the cells, as evidenced by the increased epithelial marker E-cadherin expression, and by decreased expression of mesenchymal markers N-cadherin, vimentin, fibronectin and α-SMA, as well as transcriptional repressors Snail, Slug and Twist. Physcion suppressed the expression of SOX2, whereas overexpression of SOX2 abrogated the inhibition of physcion on metastatic behaviors. Physcion markedly increased ROS production and phosphorylation of AMPK and GSK3β in the cells, whereas the AMPK inhibitor compound C or the ROS inhibitor NAC abolished the inhibition of physcion on metastatic behaviors. Conclusion: Physcion inhibits the metastatic potential of human colorectal cancer cells in vitro via activating ROS/AMPK/GSK3β signaling pathways and suppressing SOX2.

The application of traditional photodynamic therapy (PDT) is hindered by poor tissue penetration of external light and adaptive immune resistance. Here, we report an albumin-based chemiexcited photodynamic nanoreactor (CC@HSA/GOX@Z(Arg/1-MT)m) for anticancer therapy. Photosensitizer Ce6 and CPPO were incorporated into the hydrophobic domains of human serum albumin (HSA). High concentration of H2O2 reacts with CPPO to activate Ce6, generating singlet oxygen for immunogenic cell death (ICD) induction. This process fostered an immune-promoting tumor microenvironment, characterized by enhanced intratumoral infiltration of cytotoxic T lymphocytes, and a reduction in immunosuppressive cell infiltration. However, due to persistent stimulation of tumor antigens induced by ICD, the expression of IDO in the tumor was also upregulated. This upregulation contributed to the development of immune tolerance to subsequent treatments and limited the efficacy of immunotherapy. The addition of IDO inhibitor can compensate for this defect. CC@HSA/GOX@Z(Arg/1-MT)m could maintain its immune-promoting effects and alleviate post-treatment immune tolerance induced by elevated IDO expression. These findings demonstrated that the combination of IDO inhibitor and PDT represents a promising strategy for enhancing the immune response and ultimately inhibiting tumor growth.

BACKGROUND:The transcription factor (TF) MYB is crucial to many biological processes. Single-stranded DNA binding protein 2 (SSBP2), insulin gene enhancer protein 1 (ISL1) and glycolysis participated in the development of gastric cancer (GC). This study aims to explore the regulatory mechanism of the MYB/SSBP2/ISL1 axis in the development of GC. METHODS:The dataset GSE65801 of cancer tissue and paracancerous tissue samples from patients with GC was used to screen differential genes, identify GC-related key TFs and the target gene of TFs, and perform expression and survival correlation analysis. Subsequently, the expression was verified in GC tissues and cells by RT-qPCR, IHC and Western blot. CCK-8, cloning, Transwell, wound healing assay, flow cytometry and Kits testing detected the effects on cells. EMSA, Yeast one-hybrid, dual-luciferase assays, ChIP-seq analysis and ChIP-PCR analysis were used to verify transcription factor binding, and pull-down assay, CO-IP, and immunofluorescence (IF) were employed to confirm interaction. MYB action was further assessed by subcutaneous tumour experiments in nude mice. RESULTS:MYB is the key differential expression TF in GC, and SSBP2 is a key target gene of MYB. MYB had a higher expression, but SSBP2 had a lower expression in GC patients' gastric cancer tissue. SSBP2 is a direct target of MYB in GC cells. SSBP2 was transcriptionally repressed by MYB. SSBP2 further negatively regulates ISL1 expression. MYB knockdown inhibited glycolysis, proliferation, invasion, and migration abilities in GC cells both in vivo and in vitro, but it was also reversed by SSBP2 knockdown. SSBP2 overexpression inhibits glycolysis, cell proliferation, invasion and migration abilities in GC cells, but it was reversed by ISL1 overexpression. CONCLUSION:MYB mediates glycolysis and malignant progression in GC cells through regulation of the SSBP2/ISL1 axis.

Pd/CeO2 with different crystal faces can significantly affect the methane oxidation process, but the catalytic behavior in electric field is not clear yet. The supported Pd/CeO2 with rod, octahedral and cubic morphologies were synthesized by hydrothermal method, and their methane oxidation efficiency in electric field was measured. The structure of Pd/CeO2 and reaction mechanism in electric field were investigated by XRD, BET, XPS, H2-TPR, TEM and in situ DRIFTs. Studies show that the synergistic effect between electric field and (1 1 1) crystal plane in octahedral CeO2 is the strongest and (1 1 0) in rod CeO2 is the main active restraint crystal plane. The Pd atoms on the surface of Pd/CeO2-oct are exposed to the most amount of Pd atoms and the main Pd nanoparticles are present. Pd species on CeO2-cube and CeO2-rod surface with relatively low activity exist mainly in the form of Pd2+ and Pd4+, whereas Pd0 and Pd2+ on the Pd/CeO2-oct surface are more favorable for CH4 oxidation in the catalytic cycle. Pd4+ is inactive for CH4 oxidation. In addition, H migration from Pd active site to the support induced by hydrogen spillover can enhance the oxidation activity of CH4 in electric field. The conversion of carbonate/hydrogencarbonate to formate is an advantageous step in the methane oxidation process, with the active sequence being octahedral (1 1 1) > cubic (1 0 0) > rod (1 1 0) faces in/without electric field.

The high level of tyrosinase leads to the generation of neuromelanin, further causing the abnormality of redox-related protein level and mediating the occurrence and development of Parkinson's disease (PD). However, the existing tyrosinase inhibitors are mostly natural product extracts or polyphenolic derivatives, which hindered them from penetrating the blood-brain barrier (BBB). Herein, we obtained a novel tyrosinase inhibitor, 2-06 (tyrosinase: monophenolase IC50 = 70.44 ± 22.69 μM, diphenolase IC50 = 1.89 ± 0.64 μM), through the structure-based screening method. The compound 2-06 presented good in vitro and in vivo safety, and can inhibit the tyrosinase and melanogenesis in B16F10. Moreover, this compound showed neuroprotective effects and Parkinsonism behavior improving function. 2-06 was proved to penetrate the BBB and enter the central nervous system (CNS). The exploration of the binding mode between 2-06 and tyrosinase provided the foundation for the subsequent structural optimization. This is the first research to develop a central-targeting tyrosinase inhibitor, which is crucial for in-depth study on the new strategy for utilizing tyrosinase inhibitors to treat PD.

Angelica sinensis is a perennial herb widely distributed around the world, and angelica polysaccharide (APS) is a polysaccharide extracted from Angelica sinensis. APS is one of the main active components of Angelica sinensis. A large number of studies have shown that APS has hematopoietic, promoting blood circulation, radiation resistance, lowering blood glucose, enhancing the body immunity and other pharmacological effects in a variety of diseases. However, different extraction methods and extraction sites greatly affect the efficacy of APS. In recent years, with the emerging of new technologies, there are more and more studies on the combined application and structural modification of APS. In order to promote the comprehensive development and in-depth application of APS, this narrative review systematically summarizes the effects of different drying methods and extraction sites on the biological activity of APS, and the application of APS in the treatment of diseases, hoping to provide a scientific basis for the experimental study and clinical application of APS.

Considerable attention has been directed towards exploring the potential efficacy of miR-155 in the realm of cancer immunotherapy. Elevated levels of miR-155 in dendritic cells (DCs) have been shown to enhance their maturation, migration, cytokine secretion, and their ability to promote T cell activation. In addition, overexpression of mir155 in M2 macrophages boost the polarization towards the M1 phenotype. Conversely, miR-155 has the propensity to induce the accumulation of immunosuppressive cells like regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) in the tumor tissue. To account for this discrepancy, it is imperative to get help from a drug that could deal with immunosuppressive effect. Curcumin (CUR) exhibits the capacity to prompt Tregs converse into T helper 1 cells, fostering the polarization of M2 tumor-associated macrophage towards the M1 phenotype, and impeding the recruitment and aggregation of MDSCs within the tumor microenvironment. Nonetheless, CUR is known to exert an immunosuppressive impact on DCs by hindering the expression of maturation markers, cytokines, and chemokines, thereby prevent DCs response to immunostimulatory agents. Hence, a reactive oxygen species/glutathione dual responsive drug conveyance platform (CUR/miR155@DssD-Hb NPs) was devised to co-deliver CUR and miR155, with the aim of exploring their synergistic potential in bolstering a sustained and robust anti-tumor immune response. In vitro and in vivo results have suggested that CUR/miR155@DssD-Hb NPs can effectively inhibit the viability of 4T1 and B16F10 tumor cells, trigger the release of damage associated molecular patterns, stimulate DCs maturation, subsequent activation of CD8+ T cells, diminish immunosuppressive cell populations (MDSCs, Tregs, M2 TAMs and exhausted T cells), promote the formation of long-term immunity and lessen the formation of metastatic nodules in the lungs. In summary, the co-delivery system integrating CUR and miR155 (CUR/miR155@DssD-Hb NPs) demonstrates promise as a promising strategy for the immunotherapy of melanoma and triple negative breast cancer.

Many chemotherapeutic agents can induce immunogenic cell death (ICD), which leads to the release of danger-associated molecular patterns (DAMPs) and tumor-associated antigens. This process promotes dendritic cells (DCs) maturation and cytotoxic T lymphocyte (CTL) infiltration. However, cancer cells can employ diverse mechanisms to evade the host immune system. Recent studies have shown that stimulator of interferon genes (STING) agonists, such as cGAMP, can amplify ICD-triggered immune responses and enhance the infiltration of immune cells into the tumor microenvironment (TME). Building upon these findings, we constructed a doxorubicin (DOX) and cGAMP co-delivery system (DOX/cGAMP@NPs) for melanoma and triple-negative breast cancer (TNBC) therapy. The results demonstrated that DOX could effectively destroy tumors and induce the release of DAMPs by ICD. Furthermore, in orthotopic 4T1 tumors mice model and subcutaneous B16 tumor mice model, cGAMP could promote the maturation of DCs and CD8+ T cell activation and infiltration by inducing the secretion of type I interferons and pro-inflammation cytokine, which amplified the antitumor immune response induced by DOX. This strategy also promoted the depletion of immunosuppressive cells, potentially alleviating the immunosuppressive TME. In conclusion, our study highlights the combination of DOX-induced ICD and the immune-enhancing properties of cGAMP holds significant implications for future research and clinical applications.

Triple-negative breast cancer (TNBC) remains the second most-life-threatening carcinoma to women worldwide. Compared to conventional chemotherapeutic drugs, natural compounds, especially curcumin (CUR), have been proven to have therapeutical potential in TNBC treatment. To improve the accumulation of CUR at tumor sites, a reactive oxygen species (ROS)-responsive nanocarrier was developed (CUR@Bio/PE-NPs) with CUR entrapment and biotin conjugation, exhibiting a strong affinity for breast cancer cells. CUR@Bio/PE-NPs demonstrated a particle size of 142.9 nm, good stability, and an encapsulation efficiency of 63.67%, while realizing a positive feedback loop of ROS-accelerated CUR release and CUR-induced ROS generation in tumor cells. In vitro studies revealed that CUR@Bio/PE-NPs induced ROS generation effectively and promoted similar to 1.30- and 1.36-fold cellular uptake of Nile red@Bio/PE-NPs compared to nontargeted nanoparticles in MDA-MB-231 and 4T1 cells, respectively. In addition, CUR@Bio/PE-NPs suppressed their proliferation (IC50, MDA-MB-231:3.277 mu g/mL, 4T1:5.259 mu g/mL) with increased apoptosis and cell cycle arrest while preventing cell-migration and invasion. Importantly, in a 4T1 tumor xenografted mice model, nanoformulation prolonged curcumin accumulation at tumor sites, modulated the tumor immune microenvironment and prevented tumor growth and lung metastases without significant toxicity. In short, the in vitro and in vivo results suggested CUR@Bio/PE-NPs as a promising strategy for TNBC therapy.

Objective To explore the efficacy of Si-jun-zi Decoction in treating alcoholic liver disease and its mechanism. Methods Male C57BL/6 mice were randomly divided into normal group (group A), alcohol model group (group B), low-dose Si-jun-zi Decoction group (group C), and high-dose Si-jun-zi Decoction group (group D). Mice in the groups B-D were intragastrically administered ethanol solution (6 g/kg) with a volume fraction of 0.56 per day, while mice in group A were intragastrically administered an equal dose of normal saline per day. Meanwhile, mice in groups C and D were given Si-jun-zi Decoction at 5 and 10 g/kg per day, respectively. The body mass was measured once every 5 d. The experiment lasted for 18 d. After gavage, fresh feces were collected to analyze the changes in intestinal flora by 16S rDNA gene sequencing. After anesthesia, blood was collected from the canthus, and serum was collected for intestinal permeability test. Blood, liver, and spleen tissues were collected. The liver and spleen indices as well as the content of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (T-BIL), alkaline phosphatase (ALP), triglyceride (TG), and total cholesterol (TC) were measured in each group. The morphological changes of liver and spleen were observed in each group using hematoxylin-eosin and oil red O staining. Results Compared with group B, group D had significantly different body mass and liver and spleen indices (t=3.53-4.41,P<0.05), and significantly lower serum ALP, T-BIL, and TG levels (t=3.51-5.60,P<0.05). Compared with group B, groups C and D had significantly decreased serum ALT, AST, and TC levels (t=2.19-7.62,P<0.05). The pathological results showed that compared with group B, the morphology of hepatic cords in the liver tissues of groups C and D were back to normal, and the accumulation of liver fat was reduced; the red marrow and white marrow in the spleen tissue were clearly demarcated. The results of intestinal permeability showed that the intestinal permeability of group D was significantly lower than that of group B (t=3.19,P<0.05). The results of intestinal flora showed that compared with group B, the diversity of intestinal flora in mice of groups C and D was increased, with the content of beneficial bacteria such as Dubosiella,Bifidobacterium, and Allobaculum increased and that of pathogenic bacteria such as Prevotellaceae_UCG-001 and Alloprevotella decreased. Conclusion Si-jun-zi Decoction effectively ameliorates alcohol-induced liver injury in mice. The mechanism may be achieved by regulating intestinal flora.

Background:Triple negative breast cancer (TNBC) is one of the most aggressive tumors with high metastasis and mortality, which constitutes 15~20% of all breast cancers. Chemotherapy remains main therapeutic option in the treatment of patients with TNBC.Methods:We developed reactive oxygen species (ROS)-responsive galactosylated nanoparticles (DOX@NPs) as an efficiently targeted carrier for doxorubicin (DOX) delivery to inhibit the growth of TNBC in vitro and in vivo. DOX@NPs were composed of polyacrylate galactose and phenylboronic derivatives conjugation. The in vitro cytotoxicity, cellular uptake, cell apoptosis and cycle distribution of tumor cells treated with different formulations were investigated. Meanwhile in vivo biodistribution and antitumor effects were investigated in a 4T1 tumor-bearing mouse model.Results:DOX@NPs showed good ROS responsiveness and rapid DOX release in the presence of H2O2. Furthermore, our data suggested that DOX@NPs could effectively trigger tumor cells apoptosis and cycle arrest, efficiently accumulate into tumor sites, and suppress tumor growth without adverse side effects.Conclusion:Our results suggested DOX@NP with potent potential as a promising nanocarrier for TNBC therapy, which deserved further investigation for other cancer treatment.

Objective To investigate the effect of cryptotanshinone (CPT) on the apoptosis of HepG2 cells and the underlying mechanism. Methods The MTT assay was used to measure the effects of CPT at final concentrations of 0, 1, 5, 10, 20, 40, and 100 μmol/L on the viability of HepG2 cells. The median lethal concentration (IC50) of CPT for HepG2 cells was calculated. HepG2 cells were divided into groups A to D for 48 h culture with CPT at final concentrations of 0, 1, 5, and 10 μmol/L, respectively. The migration ability, mitochondrial membrane potential, and apoptosis rate of HepG2 cells were determined by wound healing assay, JC-1 staining, and flow cytometry, respectively. HepG2 cells were divided into groups E to H for culture with 0 μmol/L CPT+20 μmol/L Spautin-1, 1 μmol/L CPT+20 μmol/L Spautin-1, 5 μmol/L CPT+20 μmol/L Spautin-1, 10 μmol/L CPT+20 μmol/L Spautin-1, respectively. After 48 h culture, cell viability in groups E to H was measured by the MTT assay; LC3B-Ⅱ protein expression in groups A, D, and H was determined by Western blot; the mitochondrial membrane potential in groups A, D, E, and H was measured with JC-1 staining; and cell apoptosis in groups A, D, E, and H was measured by flow cytometry. Results With the increase of CPT concentrations, the viability of HepG2 cells was decreased significantly, with the IC50 value being 3.9 μmol/L after 48 h culture. As CPT concentrations increased, the migration ability of HepG2 cells was decreased significantly (t=5.96-29.63,P<0.05); the green/red fluorescence ratio was increased significantly (t=4.24-23.36,P<0.05); the apoptosis rate of HepG2 cells was increased significantly (t=7.30-18.15,P<0.05). There was a significant difference in cell viability between groups A to H (F=231.15,P<0.05), with higher cell viability in groups E-H than in groups A-D (t=3.96-18.80,P<0.05). Group H showed significantly lower expression of the autophagy-related protein LC3B-Ⅱ than group D (t=3.51,P<0.05). The JC-1 staining results showed that groups E and H significantly differed from group D in the green/red fluorescence ratio (t=3.58,14.76,P<0.05). The results of apoptosis by flow cytometry showed significant differences between group E and group D as well as between group H and group D (t=12.38,4.99,P<0.05). Conclusion CPT can effectively inhi-bit the viability of HepG2 cells through autophagy-mediated apoptosis.

Cancer-derived small extracellular vesicles (sEVs) serve as critical mediators of cell-to-cell communication. Manzamine A (MA), a unique marine-derived alkaloid with various bioactivities, exerts anticancer effects against several kinds of tumors, but it remains unclear whether it has the same activity against breast cancer. Here, we proved that MA inhibits MDA-MB-231 and MCF-7 cell proliferation, migration, and invasion in a time- and dose-dependent manner. In addition, MA promotes autophagosome formation but suppresses autophagosome degradation in breast cancer cells. Importantly, we also found that MA stimulates sEVs secretion and increases autophagy-related protein accumulation in secreted sEVs, further potentiated by autophagy inhibitor chloroquine (CQ). Mechanistically, MA decreases the expression level of RIP1, the key upstream regulator of the autophagic pathway, and reduces the acidity of lysosome. Overexpression of RIP1 activated AKT/mTOR signaling, thus attenuating MA-induced autophagy and the corresponding secretion of autophagy-associated sEVs. Collectively, these data suggested that MA is a potential inhibitor of autophagy by preventing autophagosome turnover, and RIP1 mediates MA-induced secretory autophagy, which may be efficacious for breast cancer treatment.

Triazole scaffolds, a series of 5-membered heterocycles, are well known for their high efficacy, low toxicity, and superior pharmacokinetics. Alzheimer's disease (AD) is the first neurodegenerative disorder with complex pathological mechanisms. Triazole, as an aromatic group with three nitrogen atoms, forms polar and non-polar interactions with diverse key residues in the receptor-ligand binding procedure, and has been widely used in the molecular design in the development of anti-AD agents. Moreover, considering the simple synthesis approaches, triazole scaffolds are commonly used to link two pharmacodynamic groups in one chemical molecule, forming multi-target directed ligands (MTDLs). Furthermore, the click reaction between azide- and cyano-modified enzyme and ligand provides feasibility for the new modulator discovery, compound tissue distribution evaluation, enzyme localization, and pharmacological mechanism study, promoting the diagnosis of AD course.

Triple negative breast cancer (TNBC) remains a serious carcinoma threatening women’s life. Natural compounds such as curcumin (CUR) have been shown promising potential in TNBC therapy without conventional toxicity like chemotherapeutics. To improve the therapeutic efficacy, a pH/redox nanocarrier (CUR@PCPP NPs) was developed for tumor specific delivery of CUR. CUR@PCPP NPs demonstrated good size distribution, encapsulation efficiency and stability in physiological conditions. While PEG detachment after exposure to extracellular tumor pH, facilitated cellular uptake of CUR@PCPP NPs, which subsequently released CUR due to intracellular redox environment. Thereafter, released CUR could efficiently induce apoptosis and cycle arrest, and inhibit TNBC cells. We further verified the biodistribution and antitumor effects in vivo and the results showed that CUR@PCPP NPs demonstrated high tumor specific accumulation and effectively suppressed tumor growth without obvious toxicity.

Abstract Purpose Designing and synthesizing dual- and multi-target drugs have raised considerable interests due to their advantages in improving potencies as antitumor agents. In previous studies, our group designed and synthesized a series of novel chalcone based tubulin and histone deacetylase (HDAC) dual-targeting inhibitors. Among them, compound B8HA exhibited promising potency for the treatment of triple-negative breast cancer. In this work, we highlighted its biological evaluations in MDA-MB-231 and 4T1 cells.Methods The in vitro antiproliferative efficacies of compound B8HA against MDA-MB-231, MDA-MB-468, MCF-7, 4T1, A549, HCT-116, HT-29 and K562 were evaluated with MTT assay. Moreover, the potencies of B8HA as inhibitors of HDAC and tubulin polymerase were also evaluated in vitro and vivo.Results Comparing to the classical HDACi SAHA, B8HA has higher potency to induce apoptosis and inhibits the migratory and invasive abilities of tumor cells under the same dose in vitro and vivo. B8HA as tubulin inhibition is also able to inhibit the formation of capillary-like structures as well as to disrupt existing tubules.Conclusion These results indicated that compound B8HA is a potent inhibitor of both HDAC and tubulin, leading to excellent in vitro and in vivo antiproliferative activities.

Triple negative breast cancer (TNBC) remains a serious carcinoma threatening women's life. Natural compounds such as curcumin (CUR) have shown promising potential in TNBC therapy without conventional toxicity like chemotherapeutics. To improve the therapeutic efficiency, a pH/redox nanocarrier (CUR@PCPP NPs) was developed for tumor specific delivery of CUR. CUR@PCPP NPs showed good size distribution, encapsulation efficiency and stability under physiological conditions. Detachment of polyethylene glycol (PEG) facilitated cellular uptake of CUR@PCPP NPs after exposure to extracellular tumor pH. Subsequently CUR was released due to the intracellular redox environment. Thereafter, released CUR could efficiently induce apoptosis and cycle arrest, and inhibit TNBC cells. We further verified the biodistribution and antitumor effects in vivo and the results showed that CUR@PCPP NPs demonstrated high tumor specific accumulation and effectively suppressed tumor growth without noticeable toxicity.