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Calcium Signalling in Breast Cancer Associated Bone Pain.

Calcium (Ca2+) is involved as a signalling mediator in a broad variety of physiological processes. Some of the fastest responses in human body like neuronal action potential firing, to the slowest gene transcriptional regulation processes are controlled by pathways involving calcium signalling. Under pathological conditions these mechanisms are also involved in tumoral cells reprogramming, resulting in the altered expression of genes associated with cell proliferation, metastatisation and homing to the secondary metastatic site. On the other hand, calcium exerts a central function in nocicepti

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… Advanced analogues of 2-Aminoethoxydiphenyl borate (2-APB), a concentration-dependent SOCE modulator, were shown to block SOCE in MDA-MB-231 cells reducing their viability [ 44 ]. … On the opposite hand, silencing MCU reduces the migration and the invasion capacities in MDA-MB-231 cells [ 59 , 60 ], impairing their ability to metastasise to other sites in-vivo [ 59 ]. 3.4. …

Parthenolide Inhibits the Proliferation of MDA-T32 Papillary Thyroid Carcinoma Cells in Vitro and in Mouse Tumor Xenografts and Activates Autophagy and Apoptosis by Downregulation of the Mammalian Target of Rapamycin (mTOR)/PI3K/AKT Signaling Pathway.

BACKGROUND This study aimed to examine the effects of the sesquiterpene lactone, parthenolide, on migration, autophagy, and apoptosis of MDA-T32 human papillary thyroid carcinoma cells in vitro and in mouse tumor xenografts. MATERIAL AND METHODS Cell proliferation and viability of MDA-T32 human papillary thyroid carcinoma cells were determined by MTT assay, and cell migration was studied using a transwell assay. Fluorescence microscopy using acridine orange (AO) and ethidium bromide (EB) staining evaluated apoptosis. Transmission electron microscopy was used to study the effects of parthenolid

The anti-tumor potential of sinomenine: a narrative review.

BACKGROUND AND OBJECTIVE: Currently, chemotherapy is the main treatment for most tumors. However, drug resistance and many adverse reactions associated with chemotherapy greatly limit its use. Therefore, an increasing number of researchers have shifted the research focus the anti-tumor activity of traditional Chinese medicine. The objective of this article is to review the anti-tumor mechanism of sinomenine and its derivatives to provide a reference for further study and clinical transformation. METHODS: In this study, we searched for relevant articles on the anti-tumor mechanism of Sinomeniu

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… In Gao et al. ’s study, sinomenine upregulates PDCD4 expression by mediating miR-29; PDCD4 obstructs the JNK and MEK/ERK pathways in MDA-MB-231 cells ( 20 ). However, the ERK signalling pathway is a double-edged sword in tumors. …

The role of EMT-related lncRNA in the process of triple-negative breast cancer metastasis.

Triple-negative breast cancer (TNBC) is the most malignant and fatal subtype of breast cancer, which has characterized by negativity expression of ER, PR, and HER2. Metastasis is the main factor affecting the prognosis of TNBC, and the process of metastasis is related to abnormal activation of epithelial-mesenchymal transition (EMT). Recent studies have shown that long non-coding RNA (LncRNA) plays an important role in regulating the metastasis and invasion of TNBC. Therefore, based on the metastasis-related EMT signaling pathway, great efforts have confirmed that LncRNA is involved in the mol

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… AFAP1-AS1 | Up | Wnt/β-catenin signaling pathway | AFAP1-AS1 inhibited MDA-MB-231 cells invsion and migration via β-catenin and p-GSK3. Up-regulation AFAP1-AS1 was correlated with poor OS and DFS in TNBC. … Down-regulation of ZEB-AS1 in MDA-MB-231 cells inhibited cell proliferation and invasion. Similarly, ZEB-AS1 attenuated tumor proliferation and lung metastasis in SCID mice. …

Curcumin Rewires the Tumor Metabolic Landscape: Mechanisms and Clinical Prospects.

Metabolic reprogramming is a fundamental hallmark and a key driver of malignant tumors. By reshaping glucose, lipid, and amino acid metabolism, as well as mitochondrial function, it sustains the abnormal proliferation and survival of tumor cells, making it a crucial target for anti-tumor therapy. Curcumin, a natural multi-target compound, exhibits unique advantages in intervening in tumor metabolic reprogramming due to its low toxicity and broad-spectrum regulatory properties. In various tumor models, it can directly modulate the activity of key glycolytic enzymes, such as hexokinase 2, lactat

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… In MDA-MB-231 cells, curcumin significantly increased the levels of intracellular Fe 2+ , malondialdehyde (MDA), lipid hydroperoxide (LOOH), and ROS by promoting HO-1 hyperactivation, while simultaneously inhibiting the expression of ferritin heavy chain (FTH) and GPX4 and depleting GSH [ 100 ]. …

Functional genomics for breast cancer drug target discovery.

Breast cancer is a heterogeneous disease that develops through a multistep process via the accumulation of genetic/epigenetic alterations in various cancer-related genes. Current treatment options for breast cancer patients include surgery, radiotherapy, and chemotherapy including conventional cytotoxic and molecular-targeted anticancer drugs for each intrinsic subtype, such as endocrine therapy and antihuman epidermal growth factor receptor 2 (HER2) therapy. However, these therapies often fail to prevent recurrence and metastasis due to resistance. Overall, understanding the molecular mechani

Anti-Cancer Research Progress of Triptolide: Mechanisms of Action, Structural Modifications, Nanodelivery Systems and Clinical Challenges.

Triptolide is a bioactive diterpenoid lactone from traditional Chinese medicine with notable anti-tumor, immunosuppressive, and anti-inflammatory properties. However, its clinical utility is hampered by poor solubility, a narrow therapeutic index, and multi-organ toxicity. In response, extensive efforts have been made to improve its efficacy and safety profile. This review critically examines recent progress in Triptolide research, covering its mechanisms of action, derivative design, drug delivery systems, and cancer-specific applications. It also evaluates its clinical potential against panc

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… Under simulated tumor microenvironment conditions, TPL/NPs significantly lowered the IC 50 against MDA-MB-231 cells (4.96–9.5 μg/mL) compared to free Triptolide (28.02–31.94 μg/mL), induced higher apoptosis rates, and arrested the cell cycle at the G0/ G1 phase. …

Screening the Active Phytochemicals From Eclipta prostrata and Unraveling Their Molecular Insight Into Human Malignancies.

Current drugs against multiple human malignancies are limited, and developing new treatment strategies is improbable within a short time. So, considering the current situation, phytochemicals could be a viable option for developing chemotherapeutic agents for managing numerous types of malignancies. Therefore, we aimed to locate all phytochemicals of Eclipta prostrata and unravel their chemotherapeutic mechanisms and strategies individually. We defined 25 active compounds based on their anticancer activities after filtering through IMPPAT and literature search, and these compounds have chemoth

Identification of a DNA Methylation-Driven Genes-Based Prognostic Model and Drug Targets in Breast Cancer: In silico Screening of Therapeutic Compounds and in vitro Characterization.

DNA methylation is a vital epigenetic change that regulates gene transcription and helps to keep the genome stable. The deregulation hallmark of human cancer is often defined by aberrant DNA methylation which is critical for tumor formation and controls the expression of several tumor-associated genes. In various cancers, methylation changes such as tumor suppressor gene hypermethylation and oncogene hypomethylation are critical in tumor occurrences, especially in breast cancer. Detecting DNA methylation-driven genes and understanding the molecular features of such genes could thus help to enh

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… (D) The effects of (+)-JQ1 on the viability of MDA-MB-231 cells. (E) The IC 50 values of selected compounds in different cell lines. (F) The effects of (+)-JQ1 on apoptosis in MCF7 and MDA-MB-231 cell lines. * P < 0.05; ** P < 0.01; **** P < 0.0001. … . (+)-JQ1 showed comparable cytotoxicity in MCF7 and MDA-MB-231 cell lines, with IC 50 values of 13.57 μM and 13.72 μM, respectively. However, MCF10A cells (IC 50 = 30.74 μM) were much less sensitive to (+)-JQ1 than MCF7 and MDA-MB-231 cell lines. …

The Anti-Cancer Effect of Polyphenols against Breast Cancer and Cancer Stem Cells: Molecular Mechanisms.

The high incidence of breast cancer in developed and developing countries, and its correlation to cancer-related deaths, has prompted concerned scientists to discover novel alternatives to deal with this challenge. In this review, we will provide a brief overview of polyphenol structures and classifications, as well as on the carcinogenic process. The biology of breast cancer cells will also be discussed. The molecular mechanisms involved in the anti-cancer activities of numerous polyphenols, against a wide range of breast cancer cells, in vitro and in vivo, will be explained in detail. The in

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… Moreover, EGCG-exposed ERα-negative MDA-MB-231 cell lines, expressing mutated p53, showed a marked decrease in cell growth and up-regulation of ERα and IGF-1R, which resulted in an increased responsiveness of the cell to tamoxifen treatment [ 251 ]. … PARP cleavage was significantly induced in resveratrol-treated MDA-MB-231 cells, and was correlated with the activation of caspase-3 [ 286 ]. …

The bone-muscle connection in breast cancer: implications and therapeutic strategies to preserve musculoskeletal health.

Breast cancer and its therapies frequently result in significant musculoskeletal morbidity. Skeletal complications include bone metastases, pain, bone loss, osteoporosis, and fracture. In addition, muscle loss or weakness occurring in both the metastatic and curative setting is becoming increasingly recognized as systemic complications of disease and treatment, impacting quality of life, responsiveness to therapy, and survival. While the anatomical relationship between bone and muscle is well established, emerging research has led to new insights into the biochemical and molecular crosstalk be

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… In these studies, application of LIV results in a threefold reduction in MDA-MB-231 cell invasion through the extracellular matrix, likely mediated by decreased expression of matrix metalloproteinases that are required to degrade the matrix. … We also found that disruption of the Nucleoskeleton and Cytoskeleton (LINC) complex in MDA-MB-231 cells exposed to LIV abrogates the beneficial effects of the mechanical stimulus. …

Redefining Breast Cancer Care by Harnessing Computational Drug Repositioning.

Breast cancer faces significant therapeutic challenges, particularly for triple-negative breast cancer (TNBC), due to limited targeted therapies and drug resistance. Drug repositioning leverages existing safety and pharmacokinetic data to expedite the identification of new indications with cost-effective benefits compared to de novo drug discovery. In this critical narrative review, we examine recent advances in computational repositioning strategies for breast cancer, focusing on network-based methods, computer-aided drug design, artificial intelligence and machine learning, transcriptomic si

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… Quinacrine and irinotecan exhibited higher antiproliferative activity than lapatinib and gefitinib in MCF-7 cells; quinacrine outperformed both standard drugs in MCF-7 and MDA-MB-231 cell lines. Wnt pathway antagonists remain an unmet need in oncology. … This platform identified rifabutin as an agent for TNBC that was experimentally validated to inhibit the growth of MDA-MB-231 cells. The study of [ 79 ] presents a pathway-based analytical approach using breast cancer transcriptomic data from TCGA and METABRIC. …

Breast cancer metastasis to the bone: mechanisms of bone loss.

Breast cancer frequently metastasizes to the skeleton, interrupting the normal bone remodeling process and causing bone degradation. Osteolytic lesions are the end result of osteoclast activity; however, osteoclast differentiation and activation are mediated by osteoblast production of RANKL (receptor activator for NFκB ligand) and several osteoclastogenic cytokines. Osteoblasts themselves are negatively affected by cancer cells as evidenced by an increase in apoptosis and a decrease in proteins required for new bone formation. Thus, bone loss is due to both increased activation of osteoclasts

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… Evidence from an intratibial bone metastasis model indicates that when highly aggressive metastatic MDA-MB-231 cells express dysfunctional Runx2 or small hair-pin RNA for Runx2 , both osteoclastogenesis and osteolytic lesions decrease [ 40 ]. … Kang and colleagues [ 20 ] found that expression of two MMP genes, MMP1 and ADAMTS1 , discriminated between a subline of osteotropic metastatic MDA-MB-231 cells and the parental line. Where do the MMPs come from? Cancer cells, osteoblasts, osteoclasts and endothelial cells produce MMPs. …

Autophagic mechanisms in longevity intervention: role of natural active compounds.

The term 'autophagy' literally translates to 'self-eating' and alterations to autophagy have been identified as one of the several molecular changes that occur with aging in a variety of species. Autophagy and aging, have a complicated and multifaceted relationship that has recently come to light thanks to breakthroughs in our understanding of the various substrates of autophagy on tissue homoeostasis. Several studies have been conducted to reveal the relationship between autophagy and age-related diseases. The present review looks at a few new aspects of autophagy and speculates on how they m

From HDAC to Voltage-Gated Ion Channels: What's Next? The Long Road of Antiepileptic Drugs Repositioning in Cancer.

Cancer is a major health burden worldwide. Although the plethora of molecular targets identified in the last decades and the deriving developed treatments, which significantly improved patients' outcome, the occurrence of resistance to therapies remains the major cause of relapse and mortality. Thus, efforts in identifying new markers to be exploited as molecular targets in cancer therapy are needed. This review will first give a glance on the diagnostic and therapeutic significance of histone deacetylase (HDAC) and voltage gated ion channels (VGICs) in cancer. Nevertheless, HDAC and VGICs hav

Nanoparticles for Targeted Drug Delivery to Cancer Stem Cells: A Review of Recent Advances.

Cancer stem cells (CSCs) are a subpopulation of cells that can initiate, self-renew, and sustain tumor growth. CSCs are responsible for tumor metastasis, recurrence, and drug resistance in cancer therapy. CSCs reside within a niche maintained by multiple unique factors in the microenvironment. These factors include hypoxia, excessive levels of angiogenesis, a change of mitochondrial activity from aerobic aspiration to aerobic glycolysis, an upregulated expression of CSC biomarkers and stem cell signaling, and an elevated synthesis of the cytochromes P450 family of enzymes responsible for drug

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… In a study with MDA-MB-231 cells, PLGA NPs loaded with PTX and SLM and coated with hyaluronic acid (HLA) showed a high binding efficiency against CD44 + cells and cytotoxicity against both bulk tumor cells and CSCs [ 39 ]. 3.2. …

Stochasticity of anticancer mechanisms underlying clinical effectiveness of vorinostat.

The Food and Drug Administration (FDA) has approved vorinostat, also called Zolinza®, for its effectiveness in fighting cancer. This drug is a suberoyl-anilide hydroxamic acid belonging to the class of histone deacetylase inhibitors (HDACis). Its HDAC inhibitory potential allows it to accumulate acetylated histones. This, in turn, can restore normal gene expression in cancer cells and activate multiple signaling pathways. Experiments have proven that vorinostat induces histone acetylation and cytotoxicity in many cancer cell lines, increases the level of p21 cell cycle proteins, and enhances p

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… -231 cells in a xenograft mouse model ( in vivo ) | MTS assay | Sensitized Hs578T and TNBC MDA-MB-231 cells to AFP464 | [ 64 ] Chou-Talalay method | Enhanced AFP464 anticancer effect ( in vivo ) Western blot analysis qRT-PCR | Immunofluorescence | Immunohistochemical staining | Primary PyMT cells … After 24 h MDA MB 231 cell treatment with Vorinostat-PEG-PLGA micelles, the percentage of cell destruction was approximately 55 % compared to 36 % for the free agent. …

Withania somnifera: Progress towards a Pharmaceutical Agent for Immunomodulation and Cancer Therapeutics.

Chemotherapy is one of the prime treatment options for cancer. However, the key issues with traditional chemotherapy are recurrence of cancer, development of resistance to chemotherapeutic agents, affordability, late-stage detection, serious health consequences, and inaccessibility. Hence, there is an urgent need to find innovative and cost-effective therapies that can target multiple gene products with minimal adverse reactions. Natural phytochemicals originating from plants constitute a significant proportion of the possible therapeutic agents. In this article, we reviewed the advances and t

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… Furthermore, Withania root extracts have been shown to influence the EMT in breast cancer in in vitro and in xenograft mouse models supplemented with MDA-MB-231 cells [ 117 , 118 ]. … Interestingly, transfection of MDA-MB-231 cells with ER-α inhibited Withaferin A-induced apoptosis but failed to obstruct the Withaferin A-induced cell cycle arrest at the G2/M phase. …

Food-derived compounds targeting ferroptosis for cancer therapy: from effects to mechanisms.

Ferroptosis is distinctive type programmed cell death. Tumor cells, with their higher iron levels, render them more susceptible to ferroptosis Inducing ferroptosis can activate immune cells, regulate immune evasion, and inhibit the biology activity of cancer cells. Therefore, ferroptosis-induced cancer cell death could become a promising approach for cancer treatment. Dietary compounds are an important source for drug discovery, and there has been an increasing amount of literature on food-derived ferroptosis inducers and their applications in cancer treatment. This review provides an overview

Anti-Cancer Natural Products and Their Bioactive Compounds Inducing ER Stress-Mediated Apoptosis: A Review.

Cancer is the second biggest cause of death worldwide. Despite a number of studies being conducted, the effective mechanism for treating cancer has not yet been fully understood. The tumor-microenvironment such as hypoxia, low nutrients could disturb function of endoplasmic reticulum (ER) to maintain cellular homeostasis, ultimately leading to the accumulation of unfolded proteins in ER, so-called ER stress. The ER stress has a close relation with cancer. ER stress initiates unfolded protein response (UPR) to re-establish ER homeostasis as an adaptive pathway in cancer. However, persistent ER

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… BFA, isolated from the fungus Eupenicillium brefeldianum , upregulated PERK, CHOP, BIM and downregulated Bcl-2 in MDA-MB-231 cells. These results suggest that mitochondrial dysfunction is involved in BFA-induced ER stress-mediated apoptosis [ 116 ]. … Fucoidan (a polysaccharide extracted from brown seaweed such as Cladosiphon okamuranus and Fucus evanescens ) facilitated ER stress by activating eIF2α, CHOP along with suppressing IRE1, XBP1 in MDA-MB-231 cells. …