Naringenin Regulates FKBP4/NR3C1/NRF2 Axis in Autophagy and Proliferation of Breast Cancer and Differentiation and Maturation of Dendritic Cell

NRF2 is an important regulatory transcription factor involved in tumor immunity and tumorigenesis. In this study, we firstly identified that FKBP4/NR3C1 axis was a novel negative regulator of NRF2 in human breast cancer (BC) cells. The effect of FKBP4 appeared to be at protein level of NRF2 since it could not suppress the expression of NRF2 at mRNA level. Bioinformatics analysis and in vitro experiments further demonstrated that FKBP4 regulated NRF2 via regulating nuclear translocation of NR3C1. We then reported that naringenin, a flavonoid, widely distributed in citrus and tomato, could suppress autophagy and proliferation of BC cells through FKBP4/NR3C1/NRF2 signaling pathway in vitro and in vivo. Naringenin was also found to promote dendritic cell (DC) differentiation and maturation through FKBP4/NR3C1/NRF2 axis. Therefore, our study found that naringenin could induce inhibition of autophagy and cell proliferation in BC cells and enhance DC differentiation and maturation, at least in part, though regulation of FKBP4/NR3C1/NRF2 signaling pathway. Identification of FKBP4/NR3C1/NRF2 axis would provide insights for novel anti-tumor strategy against BC among tumor microenvironment.

Anticancer and Antimicrobial Activity of Red Sea Seaweeds Extracts-Mediated Gold Nanoparticles

Biosynthesis of gold nanoparticles (AuNPs) is emerging as a better alternative to traditional chemical-based techniques. During this study, extracts of different marine algae species Ulva rigida (green algae), Cystoseira myrica (brown Algae), and Gracilaria foliifera (red Algae) were utilized as reducing and capping agents to synthesize AuNPs. AuNPs capped by U. rigida, C. myrica, and G. foliifera were confirmed by the appearance of surface plasmonic bands at 528, 540, and 543 nm, respectively. Transmission electron microscopy revealed mostly spherical shapes of AuNPs having a size of about 9 nm, 11 nm, and 13 nm for C. myrica, and G. foliifera extracts, respectively. Fourier transform-infrared spectroscopy (FTIR) illustrated the major chemical constituents of U. rigida, C. myrica, and G. foliifera. LC50 values of the biosynthesized AuNPs against Artemia salina nauplii were calculated at a range of concentrations (5-188 μg ml−1) after 16 to 24h. AuNPs concentration-dependent lethality was noted and U. rigida extracts-mediated AuNPs presented the lowest cytotoxicity. The biosynthesized AuNPs exhibited significant anticancer activity (86.83%) against MCF-7 cell lines (human breast adenocarcinoma cell lines) at 188 µg/ml concentration. G. foliifera demonstrated the highest anticancer value (92.13%) followed by C. myrica (89.82%), and U. rigida (86.83%), respectively. The AuNPs synthesized by different algal extracts showed variable antimicrobial activity against the tested pathogenic microorganisms. AuNPs of U. rigida extracts showed significant antimicrobial activity against dermatophytic fungi Trichosporon cataneum (30 mm) followed by Trichophyton mantigrophytes (25 mm). Furthermore, it also exhibited mild activity against Escherichia coli (17 mm), Cryptococcus neoformans (15 mm), Candida albicans (13 mm), and Staphylococcus aureus (11mm), respectively whereas no effects were observed against Bacillus cereus. To conclude, AuNPs can be effectively synthesized by marine algal species, and particularly U. rigida extracts could be effective reducing agents for the green AuNPs synthesis. These AuNPs could potentially serve as efficient alternative anticancer agents against human breast adenocarcinoma and anti-dermatophytes associated with skin infections.

Characterization of cisplatin-loaded chitosan nanoparticles and rituximab-linked surfaces as target-specific injectable nano-formulations for combating cancer

The present study was carried out to develop cisplatin-loaded chitosan nanoparticles (CCNP) and cisplatin-loaded chitosan nanoparticle surface linked to rituximab (mAbCCNP) as targeted delivery formulations. The two formulations (CCNP and mAbCCNP) exhibited significant physicochemical properties. The zetapotential (ZP) values of CCNP and mAbCCNP were 30.50 ± 5.64 and 26.90 ± 9.09 mV, respectively; while their particle sizes were 308.10 ± 1.10 and 349.40 ± 3.20 z.d.nm, respectively. The poly dispersity index (PDI) of CCNP was 0.257 ± 0.030 (66.6% PDI), while that of mAbCCNP was 0.444 ± 0.007 (57.60% PDI). Differential scanning calorimetry (DSC) revealed that CCNP had endothermic peaks at temperatures ranging from 135.50 to 157.69 °C. A sharp exothermic peak was observed at 95.79 °C, and an endothermic peak was observed at 166.60 °C. The XRD study on CCNP and mAbCCNP revealed distinct peaks at 2θ. Four peaks at 35.38°, 37.47°, 49.29°, and 59.94° corresponded to CCNP, while three distinct peaks at 36.6°, 49.12°, and 55.08° corresponded to mAbCCNP. The in vitro release of cisplatin from nanoparticles followed zero order kinetics in both CCNP and mAbCCNP. The profile for CCNP showed 43.80% release of cisplatin in 6 h (R2 = 0.9322), indicating linearity of release with minimal deviation. However, the release profile of mAbCCNP showed 22.52% release in 4 h (R2 = 0.9416), indicating linearity with sustained release. In vitro cytotoxicity studies on MCF-7 ATCC human breast cancer cell line showed that CCNP exerted good cytotoxicity, with IC50 of 4.085 ± 0.065 µg/mL. However, mAbCCNP did not elicit any cytotoxic effect. At a dose of 4.00 µg/mL cisplatin induced early apoptosis and late apoptosis, chromatin condensation, while it produced secondary necrosis at a dose of 8.00 µg/mL. Potential delivery system for cisplatin CCNP and mAbCCNP were successfully formulated. The results indicated that CCNP was a more successful formulation than mAbCCNP due to lack of specificity of rituximab against MCF-7 ATCC human breast cancer cells.

Elevated SOX11 expression distinguishes basal-like human breast cancer.

Patients diagnosed with basal-like breast cancer face a more aggressive disease course and more dismal prognosis than patients diagnosed with luminal A and luminal B breast cancer molecular subtypes (1-4). We mined published microarray data (5, 6) to understand in an unbiased fashion the most distinguishing transcriptional features of tumors from patients with basal or basal-like subtype breast cancer. We observed transcriptome-wide differential expression of SRY-box 11, SOX11, when comparing tumors of patients with basal-like breast cancer with that of other PAM50 molecular subtypes. SOX11 mRNA was present at significantly higher quantities in the tumors of patients with basal-like breast cancer. Analysis of patient survival data revealed that SOX11 primary tumor expression was correlated with overall survival, with higher SOX11 associated with inferior outcomes - in basal-like patients but not in luminal A, luminal B, HER2+, or normal-like patients. Elevated SOX11 expression appears to distinguish basal-like human breast cancer from the other molecular subtypes.

Comparison of mucin-1 in human breast cancer and canine mammary gland tumor: a review study

Mucin-1 (MUC-1) is a transmembrane glycoprotein, which bears many similarities between dogs and humans. Since the existence of animal models is essential to understand the significant factors involved in breast cancer mechanisms, canine mammary tumors (CMTs) could be used as a spontaneously occurring tumor model for human studies. Accordingly, this review assessed the comparison of canine and human MUC-1 based on their diagnostic and therapeutic aspects and showed how comparative oncology approaches could provide insights into translating pre-clinical trials from human to veterinary oncology and vice versa which could benefit both humans and dogs.

High VEGF-A expression distinguishes basal-like human breast cancer.

Patients diagnosed with basal-like breast cancer face a more aggressive disease course and more dismal prognosis than patients diagnosed with luminal A and luminal B breast cancer molecular subtypes (1-4). We mined published microarray data (5, 6) to understand in an unbiased fashion the most distinguishing transcriptional features of tumors from patients with basal or basal-like subtype breast cancer. We observed transcriptome-wide differential expression of the vascular endothelial growth factor A, VEGFA, when comparing tumors of patients with basal-like breast cancer with that of other PAM50 molecular subtypes. VEGF-A mRNA was present at significantly higher quantities in the tumors of patients with basal-like breast cancer. Analysis of patient survival data revealed that VEGF-A primary tumor expression was correlated with recurrence-free survival, with higher VEGF-A associated with inferior outcomes - in basal-like patients but not in luminal A, luminal B, HER2+, or normal-like patients. High VEGF-A expression appears to distinguish basal-like human breast cancer from the other molecular subtypes.