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Next-Generation HDAC Inhibitors: Advancing Zinc-Binding Group Design for Enhanced Cancer Therapy.

Histone deacetylases (HDACs) are pivotal epigenetic regulators that control gene expression, cell proliferation, and differentiation, and their dysregulation is closely associated with the onset and progression of multiple cancers. The therapeutic importance of these enzymes is reflected by FDA approval of HDAC inhibitors for oncology indications. Despite this clinical success, most FDA-approved agents employ conventional zinc-binding groups (ZBGs) such as hydroxamic acid and 2-aminoanilide, which are frequently linked to metabolic instability, genotoxicity, and poor pharmacokinetic behavior.

Combinational Antitumor Strategies Based on the Active Ingredients of Toad Skin and Toad Venom.

A multidrug combination strategy is an important mean to improve the treatment of cancer and is the mainstream scheme of clinical cancer treatment. The active ingredients of traditional Chinese medicine, represented by toad skin and toad venom, have the advantages of high efficiency, low toxicity, wide action and multiple targets and have become ideal targets in combined treatment strategies for tumors in recent years. Toad skin and toad venom are traditional Chinese animal medicines derived from Bufo bufo gargarizans Cantor or Bufo melanostictus Schneider that have shown excellent therapeutic

Combinatorial targeting of cancer bone metastasis using mRNA engineered stem cells.

BACKGROUND: Bone metastases are common and devastating to cancer patients. Existing treatments do not specifically target the disease sites and are therefore ineffective and systemically toxic. Here we present a new strategy to treat bone metastasis by targeting both the cancer cells ("the seed"), and their surrounding niche ("the soil"), using stem cells engineered to home to the bone metastatic niche and to maximise local delivery of multiple therapeutic factors. METHODS: We used mesenchymal stem cells engineered using mRNA to simultaneously express P-selectin glycoprotein ligand-1 (PSGL-1)

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… MDA-MB-231 cells were plated in a 96-well plate at a density of 1.5 × 10 4 cells/well and treated with recombinant human TRAIL in addition to rhOPG or concentrated MSC supernatant containing an equivalent concentration of OPG (as determined by ELISA). …

Voltage-gated sodium channel as a target for metastatic risk reduction with re-purposed drugs.

ObjectiveTo determine the exact role of sodium channel proteins in migration, invasion and metastasis and understand the possible anti-invasion and anti-metastatic activity of repurposed drugs with voltage gated sodium channel blocking properties.Material and methodsA review of the published medical literature was performed searching for pharmaceuticals used in daily practice, with inhibitory activity on voltage gated sodium channels. For every drug found, the literature was reviewed in order to define if it may act against cancer cells as an anti-invasion and anti-metastatic agent and if it w

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… Yang et al. 60 found that NaV 1.5 was over-expressed in breast cancer cells with high metastatic potential, and the anticonvulsivant PHEN had the ability to reduce migration and invasion at clinically achievable concentrations in MDA-MB-231 cells (which are strongly metastatic) and showed no effects … Yang M, 2012 60 | At clinically achievable concentration PHEN inhibited migration and invasion of highly metastatic breast cancer MDA-MB-231 cell line, and had no effect on MCF-7 cell line which has a low metastatic potential and do not express VGSCs. …

An overview of the potential anticancer properties of cardamonin.

Cancer is one of the leading causes of mortality, contributing to 9.6 million deaths globally in 2018 alone. Although several cancer treatments exist, they are often associated with severe side effects and high toxicities, leaving room for significant advancements to be made in the field. In recent years, several phytochemicals from plants and natural bioresources have been extracted and tested against various human malignancies using both in vitro and in vivo preclinical model systems. Cardamonin, a chalcone extracted from the Alpinia species, is an example of a natural therapeutic agent that

Tumour-Derived Extracellular Vesicles (EVs): A Dangerous "Message in A Bottle" for Bone.

Several studies have shown the importance of Extracellular Vesicles (EVs) in the intercellular communication between tumour and resident cells. Through EVs, tumour cells can trigger cell-signalling molecules and shuttle exogenous information to target cells, thus promoting spread of the disease. In fact, many processes are fuelled by EVs, such as tumour invasion and dormancy, drug-resistance, immune-surveillance escape, extravasation, extracellular matrix remodelling and metastasis. A key element is certainly the molecular profile of the shed cargo. Understanding the biochemical basis of EVs w

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… It has been described that co-culturing bone metastatic MDA-MB-231 cells with bone marrow-mesenchymal stem cells (BM-MSCs) suppresses their proliferation as well as sensitivity to chemotherapy, thus suggesting the acquisition of a “dormant” phenotype by tumour cells. … The iRGD DXR-sEVs proved to be efficacious in reducing MDA-MB-231 cells in an orthotopic mouse model of breast cancer, showing higher efficiency and less toxicity compared to free DXR [ 118 ]. 6. …

Extracellular Vesicles in Tumors: A Potential Mediator of Bone Metastasis.

As one of the most common metastatic sites, bone has a unique microenvironment for the growth and prosperity of metastatic tumor cells. Bone metastasis is a common complication for tumor patients and accounts for 15-20% of systemic metastasis, which is only secondary to lung and liver metastasis. Cancers prone to bone metastasis include lung, breast, and prostate cancer. Extracellular vesicles (EVs) are lipid membrane vesicles released from different cell types. It is clear that EVs are associated with multiple biological phenomena and are crucial for intracellular communication by transportin

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… -231 cell | Ultracentrifugation | NTA, TEM, western blot (CD9, TSG101) | miR-940 | Microarray analysis | RT-qPCR | / | Induces extensive osteoblastic lesions | Guo et al., 2019 | MDA-MB-231 cell | Ultracentrifugation | TEM, western blot (CD63, TSG101) | miR-20a-5p/SRCIN1 | / | RT-qPCR | Osteoclasts … Interestingly, the implantation of miR-940-overexpressing MDA-MB-231 cells induced extensive osteoblastic lesions in the resultant tumors by facilitating osteogenic differentiation of host mesenchymal cells, even though MDA-MB-231 breast cancer cells have commonly been considered an osteolytic-inducing …

Current Perspectives of the Applications of Polyphenols and Flavonoids in Cancer Therapy.

The development of anticancer therapies that involve natural drugs has undergone exponential growth in recent years. Among the natural compounds that produce beneficial effects on human health, polyphenols have shown potential therapeutic applications in cancer due to their protective functions in plants, their use as food additives, and their excellent antioxidant properties. The possibility of combining conventional drugs-which are usually more aggressive than natural compounds-with polyphenols offers very valuable advantages such as the building of more efficient anticancer therapies with l

Non-coding RNA/microRNA-modulatory dietary factors and natural products for improved cancer therapy and prevention: Alkaloids, organosulfur compounds, aliphatic carboxylic acids and water-soluble vitamins.

Non-coding small RNA molecules, the microRNAs (miRNAs), contribute decisively to the epigenetic regulation processes in cancer cells. Problematic pathogenic properties of cancer cells and the response of cancers towards anticancer drugs are highly influenced by miRNAs. Both increased drug activity and formation of tumor resistance are regulated by miRNAs. Further to this, the survival and proliferation of cancer cells and the formation of metastases is based on the modulated expression of certain miRNAs. In particular, drug-resistant cancer stem-like cells (CSCs) depend on the presence and abs

Targeting Cancer Through Thymoquinone: From Molecular Mechanisms to Clinical Prospects.

Thymoquinone (TQ), the active compound in Nigella sativa (black seed), has shown promising effects against cancer in many laboratory studies. In this review, we explore how TQ works on different aspects of cancer, from stopping cancer cell growth and spread, to triggering cancer cell death, reducing inflammation, and helping the immune system fight back. We also highlight how TQ may overcome one of the biggest problems in cancer treatment-chemoresistance. When used together with common treatments like chemotherapy, radiation, or immunotherapy, TQ has been shown to improve their effects and red

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… Downregulation of CXCR4 was further correlated with the inhibition of CXCL12-mediated migration and invasion of MDA-MB-231 cells [ 35 ]. …

Strategies to overcome the main challenges of the use of CRISPR/Cas9 as a replacement for cancer therapy.

CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats-associated protein 9) shows the opportunity to treat a diverse array of untreated various genetic and complicated disorders. Therapeutic genome editing processes that target disease-causing genes or mutant genes have been greatly accelerated in recent years as a consequence of improvements in sequence-specific nuclease technology. However, the therapeutic promise of genome editing has yet to be explored entirely, many challenges persist that increase the risk of further mutations. Here, we highlighted the main challenges fa

Modulation of angiogenesis with siRNA inhibitors for novel therapeutics.

Cancer and many other serious diseases are characterized by the uncontrolled growth of new blood vessels. Recently, RNA interference (RNAi) has reinvigorated the therapeutic prospects for inhibiting gene expression and promises many advantages over binding inhibitors, including high specificity, which is essential for targeted therapeutics. This article describes the latest developments using small-interfering RNA (siRNA) inhibitors to downregulate various angiogenic and tumor-associated factors, both in cell-culture assays and in animal disease models. The majority of research efforts are cur

Revisiting Curcumin in Cancer Therapy: Recent Insights into Molecular Mechanisms, Nanoformulations, and Synergistic Combinations.

Curcumin has been extensively investigated as an anticancer agent, yet its clinical application remains constrained by low bioavailability, incomplete mechanistic understanding, and limited therapeutic optimization. In light of growing resistance to conventional chemotherapies and the demand for safer, multi-targeted agents, this review revisits curcumin with a contemporary lens. We critically evaluate the literature published since 2020, focusing on newly elucidated molecular mechanisms by which curcumin regulates tumor progression, including modulation of oncogenic signaling pathways (Wnt/β-

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… Proliferation, invasion, and migration of TNBC cells are inhibited by curcumin, including Gli1-overexpressing MDA-MB-231 cells. Furthermore, curcumin reduces the Hedgehog signaling pathway, EMT, and stemness in MDA-MB-231 cells [ 128 ]. …

Another Weapon against Cancer and Metastasis: Physical-Activity-Dependent Effects on Adiposity and Adipokines.

Physically active behavior has been associated with a reduced risk of developing certain types of cancer and improved psychological conditions for patients by reducing anxiety and depression, in turn improving the quality of life of cancer patients. On the other hand, the correlations between inactivity, sedentary behavior, and overweight and obesity with the risk of development and progression of various cancers are well studied, mainly in middle-aged and elderly subjects. In this article, we have revised the evidence on the effects of physical activity on the expression and release of the ad

An understanding of mitochondria and its role in targeting nanocarriers for diagnosis and treatment of cancer.

Nanotechnology has changed the entire paradigm of drug targeting and has shown tremendous potential in the area of cancer therapy due to its specificity. In cancer, several targets have been explored which could be utilized for the better treatment of disease. Mitochondria, the so-called powerhouse of cell, portrays significant role in the survival and death of cells, and has emerged as potential target for cancer therapy. Direct targeting and nanotechnology based approaches can be tailor-made to target mitochondria and thus improve the survival rate of patients suffering from cancer. With thi

A Preclinical Evaluation of the Antitumor Activities of Edible and Medicinal Mushrooms: A Molecular Insight.

Cancer is the leading cause of morbidity and mortality around the globe. For certain types of cancer, chemotherapy drugs have been extensively used for treatment. However, severe side effects and the development of resistance are the drawbacks of these agents. Therefore, development of new agents with no or minimal side effects is of utmost importance. In this regard, natural compounds are well recognized as drugs in several human ailments, including cancer. One class of fungi, "mushrooms," contains numerous compounds that exhibit interesting biological activities, including antitumor activity

Recent progress on the effects of microRNAs and natural products on tumor epithelial-mesenchymal transition.

Epithelial-mesenchymal transition (EMT) is a biological process of phenotypic transition of epithelial cells that can promote physiological development as well as tissue healing and repair. In recent years, cancer researchers have noted that EMT is closely related to the occurrence and development of tumors. When tumor cells undergo EMT, they can develop enhanced migration and local tissue invasion abilities, which can lead to metastatic growth. Nevertheless, two researches in NATURE deny its necessity in specific tumors and that is discussed in this review. The degree of EMT and the detection

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… Transducing miR-300 inhibitor in low-metastatic HN-4 and MCF-7 cells could induce EMT, but miR-300 could reduce TWIST expression in highly metastatic HN-12 and MDA-MB-231 cells. … Breast cancer cell EMT in MDA-MB-231 cells and MCF-7 cells is significantly inhibited by 3,6-dihydroxyflavone, by downregulating TWIST, SLUG, SNAIL, and N-CAD expression while decreasing E-CAD. As a result, tumor invasion, migration, and stem cell formation were inhibited. …

Bioactivities and Mechanisms of Action of Sinomenine and Its Derivatives: A Comprehensive Review.

Sinomenine, an isoquinoline alkaloid extracted from the roots and stems of Sinomenium acutum, has been extensively studied for its derivatives as bioactive agents. This review concentrates on the research advancements in the biological activities and action mechanisms of sinomenine-related compounds until November 2023. The findings indicate a broad spectrum of pharmacological effects, including antitumor, anti-inflammation, neuroprotection, and immunosuppressive properties. These compounds are notably effective against breast, lung, liver, and prostate cancers, exhibiting IC50 values of appro

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… Song et al. revealed that SIN (0.25–1 mM) impeded the binding of NF-κB to IκB and the nuclear translocation of NF-κB in MDA-MB-231 cells, as depicted in Figure 3 . … Moreover, 7Cc ( 11 ) had the highest selective index (SI) values for MCF-7 and MDA-MB-231 cells (15.73 and 33.57, respectively) compared to the normal human cell line MCF10A [ 69 ]. 4. Anti-Inflammatory Activity and Analgesic Activity 4.1. …

Beyond boundaries: unraveling innovative approaches to combat bone-metastatic cancers.

Evidence demonstrated that bones, liver, and lungs are the most common metastasis sites in some human malignancies, especially in prostate and breast cancers. Bone is the third most frequent target for spreading tumor cells among these organs and tissues. Patients with bone-metastatic cancers face a grim prognosis characterized by short median survival time. Current treatments have proven insufficient, as they can only inhibit metastasis or tumor progression within the bone tissues rather than providing a curative solution. Gaining a more profound comprehension of the interplay between tumor c

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… Furthermore, the gold clusters were found to suppress the formation of osteoclasts from bone marrow-derived mononuclear cells in vitro , both when activated by MDA-MB-231 cells and when induced by RANKL. … In addition, the gold clusters appeared to reduce the expression of factors related to osteolysis in MDA-MB-231 cells, consequently inhibiting the activation of the NF-κB pathway in bone marrow-derived mononuclear cells. …

Resveratrol Nanoformulations for Cancer Management: A Comprehensive Review of Disease-Specific Strategies and Clinical Translational Barriers.

Cancer remains a leading cause of mortality worldwide, highlighting the need for therapeutic strategies that reduce systemic toxicity and drug resistance. Resveratrol (RES), a natural polyphenolic stilbenoid, possesses antioxidant, anti-inflammatory, pro-apoptotic, anti-metastatic, and chemosensitizing activities. However, its clinical translation is limited by poor aqueous solubility, chemical instability, rapid metabolic clearance, and consequently low systemic bioavailability. Nanotechnology-based drug delivery systems provide a promising strategy to address these limitations. This review s