Triple-negative breast cancer (TNBC) is a kind of breast cancer that lacks estrogen, progesterone, and human epidermal growth factor receptor 2. This cancer is responsible for more than 15–20% of all breast cancers and is of particular research interest as it is therapeutically challenging mainly because of its low response to therapeutics and highly invasive nature. The non-availability of specific treatment options for TNBC is usually managed by conventional therapy, which often leads to relapse. The focus of this review is to provide up-to-date information related to TNBC epidemiology, risk factors, metastasis, different signaling pathways, and the pathways that can be blocked, immune suppressive cells of the TNBC microenvironment, current and investigation therapies, prognosis, and the role of artificial intelligence in TNBC diagnosis. The data presented in this paper may be helpful for researchers working in the field to obtain general and particular information to advance the understanding of TNBC and provide suitable disease management in the future.

Green nanotechnology is the evolution of cost-effective and environmentally friendly processes for the production of metal-based nanoparticles due to medicinal importance and economic value. The aim of the present study was to biosynthesize and characterize silver nanoparticles (AgNPs) using the seed extract of Ajwa dates (Aw). The anti-bacteriostatic activity of biosynthesized Aw–AgNPs against Gram-positive and Gram-negative bacterial strains was evaluated. The anti-biofilm activity was examined by the tissue culture plate method. Lastly, the anti-cancer potential of Aw–AgNPs was investigated against the human breast cancer cell line HCC712. UV–visible absorption spectra exhibited the plasmon resonance peak at 430 nm, with the solution undergoing rapid color changes that verified the existence of biosynthesized silver nanoparticles in the solution. TEM and SEM images illustrated that the Aw–AgNPs were spherical and between 15 and 80 nm in diameter. The reduction and stabilization of Aw–AgNPs was due to the functional groups present in the biomolecules of the Ajwa seeds, as identified by FTIR. The Aw–AgNPs exhibited significant anti-bacterial activity against all the tested bacterial strains. Moreover, the Aw–AgNPs efficiently hampered the biofilm formation of the bacterial strains and exhibited cytotoxicity at various concentrations. Overall, these findings suggest that biosynthesized Aw–AgNPs may be used as a potential therapeutic formulation against bacterial infections and breast cancer.

ATP-binding cassette transporter G2 (ABCG2) is an efflux transporter related to the clinical multidrug resistance (MDR) phenomenon. Identifying ABCG2 inhibitors could help discover extraordinary curative strategies for carcinoma remediation. Hitherto, there is no medication drug inhibiting ABCG2 transporter, notwithstanding that a considerable number of drugs have been submitted to clinical-trial and investigational phases. In the search for unprecedented chemical compounds that could inhibit the ABCG2 transporter, an in silico screening was conducted on the Naturally Occurring Plant-based Anticancer Compound-Activity-Target (NPACT) database containing 1574 compounds. Inhibitor-ABCG2 binding affinities were estimated based on molecular docking and molecular minimization (MM) calculations and compared to a co-crystallized inhibitor (BWQ) acting as a reference inhibitor. Molecular dynamics (MD) simulations pursued by molecular mechanics-generalized Born surface area (MM-GBSA) binding energy estimations were further executed for compounds with MM-GBSA//MM binding energies lower than BWQ (calc. − 60.5 kcal/mol). NPACT00968 and NPACT01545 demonstrated auspicious inhibitory activities according to binding affinities (ΔG_binding) over the 100 ns MD simulations that were nearly one and a half folds compared to BWQ (− 100.4, − 94.7, and − 62.9 kcal/mol, respectively). Throughout the 100 ns MD simulations, structural and energetical analyses unveiled outstanding stability of the ABCG2 transporter when bound with NPACT00968 and NPACT01545. In silico calculations hold a promise for those two inhibitors as drug candidates of ABCG2 transporter and emphasize that further in vitro and in vivo experiments are guaranteed. Graphical

Cancer is a major public health concern worldwide in terms of mortality. The exact reason behind the development of cancer is not understood clearly, but it is evidenced that alcohol consumption, radiation, and exposure to chemicals are main players in this pathogenesis. The current mode of treatments such as surgery, chemotherapy, and radiotherapy are effective, but, still, cancer is a major problem leading to death and other side effects. However, safer and effective treatment modules are needed to overcome the adverse effects of current treatment modules. In this regard, natural compounds have been recognized to ameliorate diseases by exerting anti-inflammatory, anti-oxidative, and anti-tumor potential through several mechanisms. Mangiferin, a xanthone C-glucoside, is found in several plant species including Mangifera indica (mango), and its role in disease prevention has been confirmed through its antioxidant and anti-inflammatory properties. Furthermore, its anti-cancer-potential mechanism has been designated through modulation of cell signaling pathways such as inflammation, angiogenesis, PI3K/AKT, apoptosis, and cell cycle. This article extensively reviews the anticancer potential of mangiferin in different cancers through the modulation of cell signaling pathways. Moreover, the synergistic effects of this compound with some commonly used anti-cancer drugs against different cancer cells are discussed. More clinical trials should be performed to reconnoiter the anti-cancer potential of this compound in human cancer treatment. Further, understanding of mechanisms of action and the safety level of this compound can help to manage diseases, including cancer.

The Bcl-2 protein has a vital function in controlling the programmed cell doom of mitochondria. If programmed cell death signals are obstructed, an imbalance between cell survival and death will occur, which is a significant reason for cancer. Therefore, the Bcl-2 protein was identified as a possible therapeutic target for carcinoma treatment. Herein, the Natural Products Atlas (NPAtlas) compounds were virtually screened, seeking potent inhibitors towards the Bcl-2 protein. The performance of AutoDock Vina software to predict the docking score and pose of the investigated compounds was first validated according to the available experimental data. Based on the validated AutoDock Vina parameters, the NPAtlas database was filtered against the Bcl-2 protein. The natural compounds with docking scores less than that of the venetoclax (calc. −10.6 kcal/mol) were submitted to MD simulations, followed by MM-GBSA binding energy calculations. According to MM-GBSA//200 ns MD simulations, saquayamycin F (NPA002200) demonstrated promising binding affinity with a ΔG_binding value of −53.9 kcal/mol towards the Bcl-2 protein when compared to venetoclax (ΔG_binding = −50.6 kcal/mol). The energetical and structural analyses showed a great constancy of the saquayamycin F inside the Bcl-2 protein active site. Moreover, the ADMET and drug-likeness features of the saquayamycin F were anticipated, indicating its good oral bioavailability. According to in silico computations, saquayamycin F is proposed to be used as a therapeutic agent against the wild-type Bcl-2 protein and warrants further experimental assays.

Garlic’s main bioactive organosulfur component, diallyl trisulfide (DATS), has been widely investigated in cancer models. However, DATS is not suitable for clinical use due to its low solubility. The current study seeks to improve DATS bioavailability and assess its chemopreventive and chemosensitizing properties in an AOM-induced colorectal cancer model. The polyethylene glycol coated Distearoylphosphatidylcholine/Cholesterol (DSPC/Chol) comprising DATS-loaded DATSL and doxorubicin (DOXO)-encapsulated DOXL liposomes was prepared and characterized. The changes in the sensitivity of DATS and DOXO by DATSL and DOXL were evaluated in RKO and HT-29 colon cancer cells. The synergistic effect of DATSL and DOXL was studied by cell proliferation assay in the combinations of IC₁₀, IC₂₅, and IC₃₅ of DATSL with the IC₁₀ of DOXL. AOM, DATSL, and DOXL were administered to different groups of mice for a period of 21 weeks. The data exhibited ~93% and ~46% entrapment efficiency of DATSL and DOXL, respectively. The size of sham liposomes was 110.5 nm, whereas DATSL and DOXL were 135.5 nm and 169 nm, respectively. DATSL and DOXL exhibited significant sensitivity in the cell proliferation experiment, lowering their IC₅₀ doses by more than 8- and 14-fold, respectively. However, the DATSL IC₁₀, IC₂₅, and IC₃₅ showed escalating chemosensitivity, and treated the cells in combination with DOXL IC₁₀. Analysis of histopathological, cancer marker enzymes, and antioxidant enzymes revealed that the high dose of DATSL pretreatment and DOXL chemotherapy is highly effective in inhibiting AOM-induced colon cancer promotion. The combination of DATSL and DOXL indicated promise as a colorectal cancer treatment in this study. Intermolecular interactions of DATS and DOXO against numerous cancer targets by molecular docking indicated MMP-9 as the most favourable target for DATS exhibiting binding energy of −4.6 kcal/mol. So far, this is the first research to demonstrate the chemopreventive as well as chemosensitizing potential of DATSL in an animal model of colorectal cancer.