Spectral analysis, in vitro cytotoxicity and antibacterial studies of bioactive principles from the leaves of Conocarpus lancifolius, a common tree of Jazan, Saudi Arabia

The objective of the present study was to analyse the bioactive compounds of the leaves of Conocarpus lancifolius (C. lancifolius). The GC-MS analysis of the hot methanolic extract of the leaves (HMEL) of C. lancifolius exhibited the bioactive compounds such as 1-(3-Methoxy-2-nitrobenzyl) iso quinoline, morphin-4-ol-6,7-dione, 1-bromo-N-methyl-, phytol, hexadecanoic acid, 2,3-dihydroxypropyl ester, 2,2':4',2”-terthiophene, ethyl iso-allocholate, caryophyllene oxide, campesterol, epiglobulol, cholestan-3-ol, 2-methylene-, (3á,5à)-, dasycarpidan-1-methanol, acetate (ester) and oleic acid, eicosyl ester. The FT-IR analysis of HMEL of C. lancifolius showed a unique peak at 3184, 2413, 1657 cm-1 representing coumaric acid, chlorogenic acid and ferulic acid. The HMEL of C. lancifolius was actively inhibiting the proliferation of breast cancer cells MCF-7 ATCC at the concentration of 72.66 ± 8.21 µg/ml as IC50 value. The HMEL of C. lancifolius also revealed a good spectrum of activity against Gram-positive and Gram-negative bacterial cultures screened in this work. The activity observed has shown more or less similar effects against screened bacteria. However, the magnitude of potentiality was significantly lesser compared to standard ciprofloxacin disc at p< 0.001 level (99% confidence intervals). Furthermore, the study demonstrating the bioactive compounds can be isolated from the leaves of C. lancifolius.

Exosomal MicroRNA-204 Derived from Bone Marrow Mesenchymal Stem Cells (BMSCs) Inhibits Cell Proliferation and Induces Apoptosis Through NF-κB Signaling Pathway in Breast Cancer

Our study intends to assess the relationship between exosomes derived from bone marrow mesenchymal stem cells (BMSC-exo) and breast cancer. BMSC-exo were isolated and characterized by transmission electron microscopy. After transfection of BMSCs with miR-204 inhibitor, breast cancer cells were incubated with BMSC-exo followed by analysis of cell proliferation by CCK-8 assay, cell apoptosis by flow cytometry, and expression of apoptosis-related protein and NF-κB signaling by western blot. The co-culture of BMSC-exo with breast cancer cells enhanced miR-204 transcription, inhibited cell proliferation and induced apoptosis. Further, BMSC-exo accelerated apoptosis as demonstrated by the increased level of Bax and casepase-3 and decreased Bcl-2 expression, as well as reduced NF-κB signaling activity. But knockdown of miR-204 abolished the effect of BMSC-exo on apoptosis and proliferation with NF-κB signaling activation. In conclusion, miR-204 from BMSC-exo restrains growth of breast cancer cell and might be a novel target for treating breast cancer.

Hydroxycamptothecin Impedes the Mesenchymal Stem Cells (MSCs)-Triggered Migrative Features of Breast Cancer Cells via Suppressing the Protein Kinase B/Mitogen-Activated Protein Kinase (AKT/MAPK) Activation in Bone Marrowmesenchymal Stem Cells

The current study aimed to dissect the impacts and mechanisms of hydroxycamptothecin on breast cancer. Collect conditioned medium from MSCs cells to apply it into the co-culture system of breast cancer cells, which were pre-treated with hydroxycamptothecin. The cell counting kit was employed to measure the proliferation potential of cells, while the phosphorylation degrees of AKT/MAPKrelated proteins were examined via Western blotting. Then the cellular migration was test by transwell. Finally, the transcriptional and translational levels of IL-6 and RANTES in cells were detected by real-time PCR and enzyme-linked immunosorbent assay. HC could remarkably influence the interplay between MSC and breast malignant cells, reduce the MSC-activated migrative behavior of breast malignant cells and impede the capability of MSC to maintain the migration of cancer cells. RANTES and IL-6 exerted a synergistic induction in the migrative feature of breast cancer cells. HC could retard the migrating activities of breast cancer cells via diminishing the RANTES and IL-6 levels. Hydroxycamptothecin could impede the proliferative and migrative activities of MSC, of which the impediment was accompanied by an inhibitory impact on the secretory production of two growth factors IL-6 and RANTES from MSC, thereby enhancing the migration of breast malignant cells.

Paeoniflorin Enhances the Sensitivity of ER-Positive Breast Cancer Cells to Tamoxifen through Promoting Sirtuin 4

Tamoxifen is an effective drug for treating patients with advanced estrogen receptor-positive (ER+) breast cancer (BC), but not for all ER + BC patients. Drug tolerance is the biggest obstacle. In this study, we designed an experiment to investigate whether paeoniflorin affects the ER + BC cell’s sensitivity to tamoxifen in the T47D and MCF-7 cell lines. Herein, we found that paeoniflorin inhibited cell proliferation without inducing apoptosis. However, it enhanced tamoxifen-induced apoptosis in both cell lines. Immunoblotting revealed that paeoniflorin significantly increased the already elevated Bax/Bcl2 protein expression ratio and the caspase 3 activity levels, both induced by tamoxifen. Paeoniflorin was also found to increase SIRT4 expression, and deletion of SIRT4 could significantly reverse the inhibition of cell proliferation induced by paeoniflorin and significantly decrease paeoniflorin-enhanced apoptosis induced by tamoxifen. Moreover, protein expression detection revealed that paeoniflorin enhanced the tamoxifen-induced inhibition of STAT3 activation. Besides, the deletion of SIRT4 could significantly increase STAT3 activation in the T47D and MCF-7 cells. In conclusion, paeoniflorin suppressed STAT3 activation to enhance the sensitivity of ER-positive breast cancer cells to tamoxifen through promoting SIRT4 expression.

Biocompatible Electrochemical Sensor Based on Platinum-Nickel Alloy Nanoparticles for In Situ Monitoring of Hydrogen Sulfide in Breast Cancer Cells

Hydrogen sulfide (H2S), an endogenous gasotransmitter, is produced in mammalian systems and is closely associated with pathological and physiological functions. Nevertheless, the complete conversion of H2S is still unpredictable owing to the limited number of sensors for accurate and quantitative detection of H2S in biological samples. In this study, we constructed a disposable electrochemical sensor based on PtNi alloy nanoparticles (PtNi NPs) for sensitive and specific in situ monitoring of H2S released by human breast cancer cells. PtNi alloy NPs with an average size of 5.6 nm were prepared by a simple hydrothermal approach. The conversion of different forms of sulfides (e.g., H2S, HS−, and S2−) under various physiological conditions hindered the direct detection of H2S in live cells. PtNi NPs catalyze the electrochemical oxidation of H2S in a neutral phosphate buffer (PB, pH 7.0). The PtNi-based sensing platform demonstrated a linear detection range of 0.013–1031 µM and the limit of detection was 0.004 µM (S/N = 3). Moreover, the PtNi sensor exhibited a sensitivity of 0.323 μA μM−1 cm−2. In addition, the stability, repeatability, reproducibility, and anti-interference ability of the PtNi sensor exhibited satisfactory results. The PtNi sensor was able to successfully quantify H2S in pond water, urine, and saliva samples. Finally, the biocompatible PtNi electrode was effectively employed for the real-time quantification of H2S released from breast cancer cells and mouse fibroblasts.

Identification of AHSA1 as a Potential Therapeutic Target for Breast Cancer: Bioinformatics Analysis and In Vitro Studies

Background: Shenling Baizhu Powder (SBP), a famous Traditional Chinese Medicine (TCM) formulation, has been widely used in the adjuvant treatment of cancers, including breast cancer. This study aims to identify potential new targets for breast cancer treatment based on the network pharmacology of SBP. Methods: By analyzing the relationship between herbs and target proteins, potential targets of multiple herbs in SBP were identified by network pharmacology analysis. Besides, by comparing the data of breast cancer tissue with normal tissue, upregulated genes in two breast cancer expression profiles were found. Thereafter, the expression level and prognosis of activator of heat shock protein 90 (HSP90) ATPase activity 1 (AHSA1) were further analyzed in breast cancer by bioinformatics analysis, and the network module of AHSA1 binding protein was constructed. Furthermore, the effect of knocking down AHSA1 on the proliferation, migration, and invasion of breast cancer cells was verified by MTT, clone formation assay, and transwell assay. Results: Vascular endothelial growth factor A (VEGFA), intercellular adhesion molecule 1 (ICAM1), chemokine (C-X-C motif) ligand 8 (CXCL8), AHSA1, and serpin family E member 1 (SERPINE1) were associated with multiple herbs in SBP. AHSA1 was remarkably upregulated in breast cancer tissues and positively correlated with poor overall survival and disease metastasis-free survival. Furthermore, knockdown of AHSA1 significantly inhibited the migration and invasion in MCF-7 and MDA-MB-231 breast cancer cells but had no obvious effect on proliferation. In addition, among the proteins that bind to AHSAl, the network composed of proteasome, chaperonin, and heat shock proteins is closely connected, and these proteins are associated with poor prognosis in a variety of cancers. Conclusion: AHSA1 is positively correlated with breast cancer progression and might act as a novel therapeutic target for breast cancer.

Extracellular Vesicles as Mediators of Therapy Resistance in the Breast Cancer Microenvironment

Resistance to various therapies, including novel immunotherapies, poses a major challenge in the management of breast cancer and is the leading cause of treatment failure. Bidirectional communication between breast cancer cells and the tumour microenvironment is now known to be an important contributor to therapy resistance. Several studies have demonstrated that crosstalk with the tumour microenvironment through extracellular vesicles is an important mechanism employed by cancer cells that leads to drug resistance via changes in protein, lipid and nucleic acid cargoes. Moreover, the cargo content enables extracellular vesicles to be used as effective biomarkers for predicting response to treatments and as potential therapeutic targets. This review summarises the literature to date regarding the role of extracellular vesicles in promoting therapy resistance in breast cancer through communication with the tumour microenvironment.