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1.
Biochemistry (Mosc) ; 89(Suppl 1): S127-S147, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38621748

RESUMEN

The strategies of future medicine are aimed to modernize and integrate quality approaches including early molecular-genetic profiling, identification of new therapeutic targets and adapting design for clinical trials, personalized drug screening (PDS) to help predict and individualize patient treatment regimens. In the past decade, organoid models have emerged as an innovative in vitro platform with the potential to realize the concept of patient-centered medicine. Organoids are spatially restricted three-dimensional clusters of cells ex vivo that self-organize into complex functional structures through genetically programmed determination, which is crucial for reconstructing the architecture of the primary tissue and organs. Currently, there are several strategies to create three-dimensional (3D) tumor systems using (i) surgically resected patient tissue (PDTOs, patient-derived tumor organoids) or (ii) single tumor cells circulating in the patient's blood. Successful application of 3D tumor models obtained by co-culturing autologous tumor organoids (PDTOs) and peripheral blood lymphocytes have been demonstrated in a number of studies. Such models simulate a 3D tumor architecture in vivo and contain all cell types characteristic of this tissue, including immune system cells and stem cells. Components of the tumor microenvironment, such as fibroblasts and immune system cells, affect tumor growth and its drug resistance. In this review, we analyzed the evolution of tumor models from two-dimensional (2D) cell cultures and laboratory animals to 3D tissue-specific tumor organoids, their significance in identifying mechanisms of antitumor response and drug resistance, and use of these models in drug screening and development of precision methods in cancer treatment.


Asunto(s)
Neoplasias , Medicina de Precisión , Animales , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Organoides , Evaluación Preclínica de Medicamentos , Microambiente Tumoral
2.
Scand J Immunol ; 99(5): e13356, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38605549

RESUMEN

In light of increasing resistance to PD1 antibody therapy among certain patient populations, there is a critical need for in-depth research. Our study assesses the synergistic effects of a MUC1 DNA vaccine and PD1 antibody for surmounting PD1 resistance, employing a murine CT26/MUC1 colon carcinoma model for this purpose. When given as a standalone treatment, PD1 antibodies showed no impact on tumour growth. Additionally, there was no change observed in the intra-tumoural T-cell ratios or in the functionality of T-cells. In contrast, the sole administration of a MUC1 DNA vaccine markedly boosted the cytotoxicity of CD8+ T cells by elevating IFN-γ and granzyme B production. Our compelling evidence highlights that combination therapy more effectively inhibited tumour growth and prolonged survival compared to either monotherapy, thus mitigating the limitations intrinsic to single-agent therapies. This enhanced efficacy was driven by a significant alteration in the tumour microenvironment, skewing it towards pro-immunogenic conditions. This assertion is backed by a raised CD8+/CD4+ T-cell ratio and a decrease in immunosuppressive MDSC and Treg cell populations. On the mechanistic front, the synergistic therapy amplified expression levels of CXCL13 in tumours, subsequently facilitating T-cell ingress into the tumour setting. In summary, our findings advocate for integrated therapy as a potent mechanism for surmounting PD1 antibody resistance, capitalizing on improved T-cell functionality and infiltration. This investigation affords critical perspectives on enhancing anti-tumour immunity through the application of innovative therapeutic strategies.


Asunto(s)
Anticuerpos , Mucina-1 , Neoplasias , Receptor de Muerte Celular Programada 1 , Vacunas de ADN , Animales , Ratones , Anticuerpos/metabolismo , Linfocitos T CD8-positivos , Línea Celular Tumoral , Mucina-1/genética , Neoplasias/metabolismo , Receptor de Muerte Celular Programada 1/metabolismo , Microambiente Tumoral
3.
Pharmacol Res ; 203: 107179, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38615876

RESUMEN

Exosomes, small yet vital extracellular vesicles, play an integral role in intercellular communication. They transport critical components, such as proteins, lipid bilayers, DNA, RNA, and glycans, to target cells. These vesicles are crucial in modulating the extracellular matrix and orchestrating signal transduction processes. In oncology, exosomes are pivotal in tumor growth, metastasis, drug resistance, and immune modulation within the tumor microenvironment. Exosomal proteins, noted for their stability and specificity, have garnered widespread attention. This review delves into the mechanisms of exosomal protein loading and their impact on tumor development, with a focus on the regulatory effects of natural products and traditional Chinese medicine on exosomal protein loading and function. These insights not only offer new strategies and methodologies for cancer treatment but also provide scientific bases and directions for future clinical applications.


Asunto(s)
Productos Biológicos , Exosomas , Medicina Tradicional China , Neoplasias , Humanos , Exosomas/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Animales , Productos Biológicos/uso terapéutico , Productos Biológicos/farmacología , Microambiente Tumoral/efectos de los fármacos
4.
Int J Biol Macromol ; 264(Pt 2): 130705, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38458300

RESUMEN

The mitochondria are known to exert significant influence on various aspects of cancer cell physiology. The suppression of mitochondrial function represents a novel avenue for the advancement of anti-cancer pharmaceuticals. The heat shock protein HSP90 functions as a versatile regulator of mitochondrial metabolism in cancer cells, rendering as a promising target for anticancer interventions. In this work, a novel acid polysaccharide named as XQZ3 was extracted from Chlorella pyrenoidosa and purified by DEAE-cellulose and gel-filtration chromatography. The structural characteristic of XQZ3 was evaluated by monosaccharides composition, methylation analysis, TEM, FT-IR, and 2D-NMR. It was found that XQZ3 with a molecular weight of 29.13 kDa was a complex branched polysaccharide with a backbone mainly composed of galactose and mannose. It exhibited good antitumor activity in vitro and in vivo by patient-derived 3D organoid models and patient-derived xenografts models. The mechanistic investigations revealed that XQZ3 specifically interacted with HSP90, impeding the activation of the HSP90/AKT/mTOR signaling cascade. This, in turn, led to the induction of mitochondrial dysfunction, autophagy, and apoptosis, ultimately resulting in the demise of cancer cells due to nutrient deprivation. This study offers a comprehensive theoretical foundation for the advancement of XQZ3, a novel polysaccharide inhibitor targeting HSP90, with potential as an effective therapeutic agent against cancer.


Asunto(s)
Chlorella , Neoplasias , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Chlorella/metabolismo , Espectroscopía Infrarroja por Transformada de Fourier , Transducción de Señal , Proteínas HSP90 de Choque Térmico/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Apoptosis , Metabolismo Energético , Mitocondrias/metabolismo , Polisacáridos/farmacología , Polisacáridos/metabolismo
5.
Phytother Res ; 38(5): 2406-2447, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38433568

RESUMEN

The epidermal growth factor receptor (EGFR) is a transmembrane receptor tyrosine kinase (RTK) that maintains normal tissues and cell signaling pathways. EGFR is overactivated and overexpressed in many malignancies, including breast, lung, pancreatic, and kidney. Further, the EGFR gene mutations and protein overexpression activate downstream signaling pathways in cancerous cells, stimulating the growth, survival, resistance to apoptosis, and progression of tumors. Anti-EGFR therapy is the potential approach for treating malignancies and has demonstrated clinical success in treating specific cancers. The recent report suggests most of the clinically used EGFR tyrosine kinase inhibitors developed resistance to the cancer cells. This perspective provides a brief overview of EGFR and its implications in cancer. We have summarized natural products-derived anticancer compounds with the mechanistic basis of tumor inhibition via the EGFR pathway. We propose that developing natural lead molecules into new anticancer agents has a bright future after clinical investigation.


Asunto(s)
Productos Biológicos , Receptores ErbB , Neoplasias , Transducción de Señal , Receptores ErbB/metabolismo , Receptores ErbB/antagonistas & inhibidores , Humanos , Transducción de Señal/efectos de los fármacos , Productos Biológicos/farmacología , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Antineoplásicos/farmacología , Animales
6.
Pharmacol Res ; 203: 107148, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38522760

RESUMEN

The gut microbiota, known as the "forgotten organ" and "human second genome," comprises a complex microecosystem. It significantly influences the development of various tumors, including colorectal, liver, stomach, breast, and lung cancers, through both direct and indirect mechanisms. These mechanisms include the "gut-liver" axis, the "lung-intestine" axis, and interactions with the immune system. The intestinal flora exhibits dual roles in cancer, both promoting and suppressing its progression. Traditional Chinese medicine (TCM) can alter cancer progression by regulating the intestinal flora. It modifies the intestinal flora's composition and structure, along with the levels of endogenous metabolites, thus affecting the intestinal barrier, immune system, and overall body metabolism. These actions contribute to TCM's significant antitumor effects. Moreover, the gut microbiota metabolizes TCM components, enhancing their antitumor properties. Therefore, exploring the interaction between TCM and the intestinal flora offers a novel perspective in understanding TCM's antitumor mechanisms. This paper succinctly reviews the association between gut flora and the development of tumors, including colorectal, liver, gastric, breast, and lung cancers. It further examines current research on the interaction between TCM and intestinal flora, with a focus on its antitumor efficacy. It identifies limitations in existing studies and suggests recommendations, providing insights into antitumor drug research and exploring TCM's antitumor effectiveness. Additionally, this paper aims to guide future research on TCM and the gut microbiota in antitumor studies.


Asunto(s)
Microbioma Gastrointestinal , Medicina Tradicional China , Neoplasias , Humanos , Neoplasias/microbiología , Neoplasias/metabolismo , Neoplasias/tratamiento farmacológico , Animales , Medicamentos Herbarios Chinos/uso terapéutico
7.
Biomed Pharmacother ; 174: 116497, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38552443

RESUMEN

The study of chemicals extracted from natural sources should be encouraged due to the significant number of cancer deaths each year and the financial burden imposed by this disease on society. The causes of almost all cancers involve a combination of lifestyle, environmental factors, and genetic and inherited factors. Modern medicine researchers are increasingly interested in traditional phytochemicals as they hold potential for new bioactive compounds with medical applications. Recent publications have provided evidence of the antitumor properties of phytochemicals, a key component of traditional Chinese medicine, thereby opening new avenues for their use in modern medicine. Various studies have demonstrated a strong correlation between apoptosis and autophagy, two critical mechanisms involved in cancer formation and regulation, indicating diverse forms of crosstalk between them. Phytochemicals have the ability to activate both pro-apoptotic and pro-autophagic pathways. Therefore, understanding how phytochemicals influence the relationship between apoptosis and autophagy is crucial for developing a new cancer treatment strategy that targets these molecular mechanisms. This review aims to explore natural phytochemicals that have demonstrated anticancer effects, focusing on their role in regulating the crosstalk between apoptosis and autophagy, which contributes to uncontrolled tumor cell growth. Additionally, the review highlights the limitations and challenges of current research methodologies while suggesting potential avenues for future research in this field.


Asunto(s)
Antioxidantes , Apoptosis , Autofagia , Neoplasias , Fitoquímicos , Humanos , Autofagia/efectos de los fármacos , Apoptosis/efectos de los fármacos , Fitoquímicos/farmacología , Fitoquímicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/metabolismo , Antioxidantes/farmacología , Animales , Antineoplásicos Fitogénicos/farmacología
8.
Bull Exp Biol Med ; 176(4): 501-504, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38491259

RESUMEN

High X-ray absorption combined with photothermal properties make bismuth nanoparticles (Bi NP) a promising agent for multimodal cancer theranostics. However, the synthesis of Bi NP by the "classical" chemical methods has numerous limitations, including potential toxicity of the produced nanomaterials. Here we studied in vitro toxicity of laser-synthesized Bi NP coated with Pluronic F-127 on mouse fibroblast cell line L929. The survival of L929 cells decreased linearly with increasing the concentration of Bi NP in a concentration range of 3-500 µg/ml; the LC50 value was 57 µg/ml. The unique combination of functional properties and moderate toxicity of the laser-synthesized Bi NP makes them a new promising platform for sensitization of multimodal cancer theranostics.


Asunto(s)
Nanopartículas del Metal , Animales , Ratones , Bismuto/toxicidad , Bismuto/química , Línea Celular Tumoral , Nanopartículas del Metal/toxicidad , Nanopartículas del Metal/química , Nanopartículas/toxicidad , Nanopartículas/química , Nanoestructuras , Neoplasias/metabolismo , Fototerapia/métodos
9.
Int J Nanomedicine ; 19: 2851-2877, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38529365

RESUMEN

Neutrophil extracellular traps (NETs) are extracellular fibers composed of deoxyribonucleic acid (DNA) and decorated proteins produced by neutrophils. Recently, NETs have been associated with the development of many diseases, including tumors. Herein, we reviewed the correlation between NETs and tumors. In addition, we detailed active compounds from traditional herbal medicine formulations that inhibit NETs, related nanodrug delivery systems, and antibodies that serve as "guiding moieties" to ensure targeted delivery to NETs. Furthermore, we discussed the strategies used by pathogenic microorganisms to evade NETs.


Asunto(s)
Trampas Extracelulares , Neoplasias , Humanos , Trampas Extracelulares/metabolismo , Neutrófilos/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Extractos Vegetales
10.
Angew Chem Int Ed Engl ; 63(18): e202400249, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38372669

RESUMEN

The cell membrane is a crucial component of cells, protecting their integrity and stability while facilitating signal transduction and information exchange. Therefore, disrupting its structure or impairing its functions can potentially cause irreversible cell damage. Presently, the tumor cell membrane is recognized as a promising therapeutic target for various treatment methods. Given the extensive research focused on cell membranes, it is both necessary and timely to discuss these developments, from materials design to specific biomedical applications. This review covers treatments based on functional materials targeting the cell membrane, ranging from well-known membrane-anchoring photodynamic therapy to recent lysosome-targeting chimaeras for protein degradation. The diverse therapeutic mechanisms are introduced in the following sections: membrane-anchoring phototherapy, self-assembly on the membrane, in situ biosynthesis on the membrane, and degradation of cell membrane proteins by chimeras. In each section, we outline the conceptual design or general structure derived from numerous studies, emphasizing representative examples to understand advancements and draw inspiration. Finally, we discuss some challenges and future directions in membrane-targeted therapy from our perspective. This review aims to engage multidisciplinary readers and encourage researchers in related fields to advance the fundamental theories and practical applications of membrane-targeting therapeutic agents.


Asunto(s)
Proteínas de la Membrana , Neoplasias , Humanos , Membrana Celular/química , Proteínas de la Membrana/metabolismo , Fototerapia , Neoplasias/metabolismo
11.
Am J Physiol Cell Physiol ; 326(4): C1226-C1236, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38406827

RESUMEN

Cancer and chemotherapy induce a severe loss of muscle mass (known as cachexia), which negatively impact cancer treatment and patient survival. The aim of the present study was to investigate whether cannabidiol (CBD) administration may potentially antagonize the effects of cisplatin in inducing muscle atrophy, using a model of myotubes in culture. Cisplatin treatment resulted in a reduction of myotube diameter (15.7 ± 0.3 vs. 22.2 ± 0.5 µm, P < 0.01) that was restored to control level with 5 µM CBD (20.1 ± 0.4 µM, P < 0.01). Protein homeostasis was severely altered with a ≈70% reduction in protein synthesis (P < 0.01) and a twofold increase in proteolysis (P < 0.05) in response to cisplatin. Both parameters were dose dependently restored by CBD cotreatment. Cisplatin treatment was associated with increased thiobarbituric acid reactive substances (TBARS) content (0.21 ± 0.03 to 0.48 ± 0.03 nmol/mg prot, P < 0.05), catalase activity (0.24 ± 0.01 vs. 0.13 ± 0.02 nmol/min/µg prot, P < 0.01), whereas CBD cotreatment normalized TBARS content to control values (0.22 ± 0.01 nmol/mg prot, P < 0.01) and reduced catalase activity (0.17 ± 0.01 nmol/min/µg prot, P < 0.05). These changes were associated with increased mRNA expression of GPX1, SOD1, SOD2, and CAT mRNA expression in response to cisplatin (P < 0.01), which was corrected by CBD cotreatment (P < 0.05). Finally, cisplatin treatment increased the mitochondrial protein content of NDUFB8, UQCRC2, COX4, and VDAC1 (involved in mitochondrial respiration and apoptosis), and CBD cotreatment restored their expression to control values. Altogether, our results demonstrated that CBD antagonize the cisplatin-induced C2C12 myotube atrophy and could be used as an adjuvant in the treatment of cancer cachexia to help maintain muscle mass and improve patient quality of life.NEW & NOTEWORTHY In an in vitro model, cisplatin treatment led to myotube atrophy associated with dysregulation of protein homeostasis and increased oxidative stress, resulting in increased apoptosis. Cotreatment with cannabidiol was able to prevent this phenotype by promoting protein homeostasis and reducing oxidative stress.


Asunto(s)
Cannabidiol , Neoplasias , Humanos , Cisplatino/toxicidad , Cannabidiol/farmacología , Cannabidiol/metabolismo , Cannabidiol/uso terapéutico , Caquexia/metabolismo , Catalasa/metabolismo , Calidad de Vida , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/farmacología , Fibras Musculares Esqueléticas/metabolismo , Atrofia Muscular/inducido químicamente , Atrofia Muscular/prevención & control , Atrofia Muscular/tratamiento farmacológico , Estrés Oxidativo , Neoplasias/metabolismo , ARN Mensajero/metabolismo
12.
Sci Rep ; 14(1): 4112, 2024 02 19.
Artículo en Inglés | MEDLINE | ID: mdl-38374190

RESUMEN

Arginine, a semi-essential amino acid, is critical for cell growth. Typically, de novo synthesis of arginine is sufficient to support cellular processes, however, it becomes vital for cancer cells that are unable to synthesise arginine due to enzyme deficiencies. Targeting this need, arginine depletion with enzymes such as arginase (ARG) has emerged as a potential cancer therapeutic strategy. Studies have proposed using high dose insulin to induce a state of hypoaminoacidaemia in the body, thereby further reducing circulating arginine levels. However, the mitogenic and metabolic properties of insulin could potentially counteract the therapeutic effects of ARG. Our study examined the combined impact of insulin and ARG on breast, lung, and ovarian cell lines, focusing on cell proliferation, metabolism, apoptosis, and autophagy. Our results showed that the influence of insulin on ARG uptake varied between cell lines but failed to promote the proliferation of ARG-treated cells or aid recovery post-ARG treatment. Moreover, insulin was largely ineffective in altering ARG-induced metabolic changes and did not prevent apoptosis. In vitro, at least, these findings imply that insulin does not offer a growth or survival benefit to cancer cells being treated with ARG.


Asunto(s)
Arginasa , Insulina , Neoplasias , Humanos , Apoptosis , Arginasa/metabolismo , Arginina/metabolismo , Insulina/farmacología , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo
13.
Adv Healthc Mater ; 13(11): e2303779, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38288884

RESUMEN

Nanomaterials that generate reactive oxygen species (ROS) upon light irradiation have significant applications in various fields, including photodynamic therapy (PDT) that is widely recognized as a highly momentous strategy for the eradication of cancer cells. However, the ROS production rate of photosensitizers, as well as the tumor hypoxia environment, are two major challenges that restrict the widespread application of PDT. In this study, a cancer-thylakoid hybrid membrane-camouflaged thulium oxide nanoparticles (Tm2O3) for tumor-homing phototherapy through dual-stage-light-guided ROS generation and oxygen self-supply is developed. Tm2O3 as a type II photosensitizer are viable for NIR-stimulated ROS generation due to the unique energy levels, large absorption cross section, and long lifetime of the 3H4 state of Tm ions. The thylakoid membrane (TK) plays a catalase-like role in converting hydrogen peroxide into oxygen and also acts as a natural photosensitizer that can generate lethal ROS through electron transfer when exposed to light. In addition, fluorescence dye DiR is embedded in the hybrid membrane for in vivo tracing as well as photothermal therapy. Results show that tumors in Tm2O3@TK-M/DiR group are effectively ablated following dual-stage-light irradiation, highlighting the promising potential of rare-earth element-based type II photosensitizers in various applications.


Asunto(s)
Nanopartículas , Oxígeno , Fotoquimioterapia , Fármacos Fotosensibilizantes , Especies Reactivas de Oxígeno , Tulio , Animales , Tulio/química , Especies Reactivas de Oxígeno/metabolismo , Ratones , Humanos , Oxígeno/química , Oxígeno/metabolismo , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Nanopartículas/química , Fotoquimioterapia/métodos , Óxidos/química , Línea Celular Tumoral , Ratones Endogámicos BALB C , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/metabolismo , Fototerapia/métodos
14.
Med Oncol ; 41(3): 66, 2024 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-38281254

RESUMEN

Targeting programmed cell death (PCD) has been emerging as a promising therapeutic strategy in cancer. Pyroptosis, as a type of PCDs, leads to the cleavage of the gasdermin family and the secretion of pro-inflammatory factors. Gasdermin D (GSDMD) and gasdermin E (GSDME) are the two main executors of pyroptosis. Pyroptosis in tumor and immune cells is essential for tumor progression. Natural products, especially Chinese medicinal herb and their bioactive compounds have recently been regarded as anti-tumor agents that regulate cell pyroptosis under different circumstances. Here, we review the underlying mechanisms of natural products that activate pyroptosis in tumor cells and inhibit pyroptosis in immune cells. Pyroptosis activation in tumor cells leads to tumor cell death, yet pyroptosis inhibition in immune cells may prevent tumor occurrence. Elucidation of the signaling pathways involved in pyroptosis contributes to the understanding of the anti-tumor role of natural products and their potential clinical applications. Therefore, we outline a promising strategy for cancer therapy and prevention using natural products via modulation of pyroptosis.


Asunto(s)
Productos Biológicos , Neoplasias , Humanos , Piroptosis , Productos Biológicos/farmacología , Productos Biológicos/uso terapéutico , Gasderminas , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Apoptosis , Neoplasias/tratamiento farmacológico , Neoplasias/prevención & control , Neoplasias/metabolismo
15.
J Ethnopharmacol ; 324: 117811, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38286156

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Traditionally, the roots of Kaempferia galanga has been used to treat high blood pressure, chest pain, headache, toothache, rheumatism, indigestion, cough, inflammation and cancer in Asia. Nevertheless, most of its pharmacological studies were focused on ethanolic extracts and volatile oils. The exact active chemical constituents and their underlying mechanisms are still poorly understood, especially towards its anti-cancer treatment. Inhibition of angiogenesis is an important atrategy to inhibit tumor growth. It has been reported that the low polar component of the plant possessed anti-angiogenic activity. Yet, the potent compound which is responsible for the effect and its molecular mechanism has not been reported. AIM OF THE STUDY: To determine the potent anti-angiogenic component in K.galanga and its mechanism of action. MATERIAL AND METHODS: The low polar components of the plant were concentrated using the methods of supercritical fluid extraction (SFE), subcritical extraction (SCE) and steam distillation (SD). The anti-angiogenic activity of the three extracts was evaluated using a zebrafish model. The content of the active compound in those extracts was determined with HPLC analysis. The in-vitro and in-vivo activity of the isolated compound was evaluated using human umbilical vein endothelial cells (HUVECs) model, the aortic ring assay and the matrigel plug assay, respectively. Its molecular mechanism was further studied by the western blotting assay and computer-docking experiments. Besides, its cytotoxicity on cancer and normal cell lines was evaluated using the cell-counting kit. RESULTS: HPLC results showed that trans-ethyl p-methoxycinnamate (TEM) was the major component of the extracts. The extract of SFE showed the best effect as it has the highest content of TEM. TEM could inhibit vascular endothelial growth factor (VEGF)-induced viability, migration, invasion and tube formation in human umbilical vein endothelial cells (HUVECs) in vitro. Moreover, it inhibited VEGF-induced sprout formation ex vivo and vessel formation in vivo. Mechanistic study showed that it could suppress tyrosine kinase activity of the receptor of VEGF (VEGFR2) and alter its downstream signaling pathways. In addition, the molecular docking showed that the binding of TEM and VEGFR2 is stable, which mainly attributed to the non-covalent binding interaction. Beside, TEM possessed little toxicity to both cancer and normal cells. CONCLUSION: TEM is the major anti-angiogenic component present in K. galanga and its anti-angiogenic property rather than toxicity provides scientific basis for the traditional use of K. galanga in cancer treatment.


Asunto(s)
Alpinia , Neoplasias , Zingiberaceae , Animales , Humanos , Factor A de Crecimiento Endotelial Vascular/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Extractos Vegetales/química , Pez Cebra , Simulación del Acoplamiento Molecular , Zingiberaceae/química , Células Endoteliales de la Vena Umbilical Humana , Neoplasias/metabolismo , Inhibidores de la Angiogénesis/farmacología , Inhibidores de la Angiogénesis/uso terapéutico , Movimiento Celular , Proliferación Celular , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo
16.
Naunyn Schmiedebergs Arch Pharmacol ; 397(7): 4961-4979, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38180556

RESUMEN

Sesamol (SM), a well-known component isolated from sesame seeds (Sesamum indicum), used in traditional medicines in treating numerous ailments. However, numerous molecular investigations revealed the various mechanisms behind its activity, emphasizing its antiproliferative, anti-inflammatory, and apoptosis-inducing properties, preventing cancer cell spread to distant organs. In several cells derived from various malignant tissues, SM-regulated signal transduction pathways and cellular targets have been identified. This review paper comprehensively describes the anticancer properties of SM and SM-viable anticancer drugs. Additionally, the interactions of this natural substance with standard anticancer drugs are examined, and the benefits of using nanotechnology in SM applications are explored. This makes SM a prime example of how ethnopharmacological knowledge can be applied to the development of contemporary drugs.


Asunto(s)
Benzodioxoles , Fenoles , Humanos , Benzodioxoles/farmacología , Fenoles/farmacología , Fenoles/química , Animales , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/metabolismo , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos/farmacología , Antineoplásicos/química , Apoptosis/efectos de los fármacos
17.
Small ; 20(1): e2304491, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37653587

RESUMEN

A composite nanoagent capable of phototriggered tumor microenvironment (TME) regulation is developed based on copper (II) metal-organic frameworks (MOFs) with encapsulation of blebbistatin (Bb) and surface modification of fibroblast activation protein-αtargeted peptide (Tp). Tp enables active targeting of the nanoagents to cancer-associated fibroblast (CAF) while near-infrared light triggers Cu2+ -to-Cu+ photoreduction in MOFs, which brings about the collapse of MOFs and the release of Bb and Cu+ . Bb mediates photogeneration of hydroxyl radicals (•OH) and therefore inhibits extracellular matrix production by inducing CAF apoptosis, which facilitates the penetration of nanoagent to deep tumor tissue. The dual-channel generation of •OH based on Bb and the Cu+ species, via distinct mechanisms, synergistically reinforces oxidative stress in TME capable of inducing immunogenic cell death, which activates the antitumor immune response and therefore reverses the immunosuppressive TME. The synergistic antitumor phototherapy efficacy of such a type of nanoagent based on the abovementioned TME remodeling is unequivocally verified in a cell-derived tumor xenograft model.


Asunto(s)
Fibroblastos Asociados al Cáncer , Estructuras Metalorgánicas , Neoplasias , Humanos , Estructuras Metalorgánicas/metabolismo , Fibroblastos Asociados al Cáncer/metabolismo , Microambiente Tumoral , Cobre/metabolismo , Neoplasias/metabolismo , Línea Celular Tumoral
18.
Postgrad Med J ; 100(1180): 96-105, 2024 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-37978049

RESUMEN

PURPOSE: We aimed to investigate the pharmacological effects and mechanisms of the Aitongping formula for treating cancer pain. METHODS: We enrolled 60 cancer patients with Numeric Rating Scale above 4 and grouped them randomly as a Control group (N = 30) and a Patch group (N = 30). We also established bone cancer mice models via tumor implantation. And the animal groups were established as a Sham group, a tumor cell implantation (TCI) group, a TCI + Patch group, and a Patch group. RESULTS: After the validation of successful tumor implantation, we identified candidate miRNAs and genes that were dysregulated in TCI mice and compared their expressions between different mice groups. We also observed the effect of Aitongping patch in vitro in mice primary microglia. The time to disease progression and cancer stability were prolonged by Aitongping patch in cancer patients. And the daily morphine dose was lower, and patients' quality of life was improved in the Patch group. Moreover, Aitongping patch alleviated cancer pain and inhibited microglia activation after the successful implantation of bone tumor in TCI mice. We also observed the dysregulation of miR-150-5p and chemokine CXC motif ligand 12 (CXCL12) mRNA in TCI mice. And CXCL12 was found to be targeted by miR-150-5p. Aitongping patch was found to upregulate miR-150-5p and downregulate CXCL12 in vivo and in vitro. CONCLUSION: Aitongping patch could alleviate cancer pain via suppressing microglia activation, and the downregulation of miR-150-5p, as well as the upregulation of CXCL12 mRNA and protein, induced by tumor implantation or lipopolysaccharide stimulation, was restored by Aitongping treatment.


Asunto(s)
Dolor en Cáncer , MicroARNs , Neoplasias , Humanos , Ratones , Animales , Dolor en Cáncer/tratamiento farmacológico , Microglía/metabolismo , Calidad de Vida , MicroARNs/genética , Neoplasias/metabolismo , ARN Mensajero/metabolismo , Quimiocina CXCL12/genética , Quimiocina CXCL12/metabolismo
19.
Phytother Res ; 38(2): 880-911, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38088265

RESUMEN

Current pharmaceutical research is energetically excavating the pharmacotherapeutic role of herb-derived ingredients in multiple malignancies' targeting. Luteolin is one of the major phytochemical components that exist in various traditional Chinese medicine or medical herbs. Mounting evidence reveals that this phytoconstituent endows prominent therapeutic actions on diverse malignancies, with the underlying mechanisms, combined medication strategy, and pharmacokinetics elusive. Additionally, the clinical trial and pharmaceutical investigation of luteolin remain to be systematically delineated. The present review aimed to comprehensively summarize the updated information with regard to the anticancer mechanism, combined medication strategies, pharmacokinetics, clinical trials, and pharmaceutical researches of luteolin. The survey corroborates that luteolin executes multiple anticancer effects mainly by dampening proliferation and invasion, spurring apoptosis, intercepting cell cycle, regulating autophagy and immune, inhibiting inflammatory response, inducing ferroptosis, and pyroptosis, as well as epigenetic modification, and so on. Luteolin can be applied in combination with numerous clinical anticarcinogens and natural ingredients to synergistically enhance the therapeutic efficacy of malignancies while reducing adverse reactions. For pharmacokinetics, luteolin has an unfavorable oral bioavailability, it mainly persists in plasma as glucuronides and sulfate-conjugates after being metabolized, and is regarded as potent inhibitors of OATP1B1 and OATP2B1, which may be messed with the pharmacokinetic interactions of miscellaneous bioactive substances in vivo. Besides, pharmaceutical innovation of luteolin with leading-edge drug delivery systems such as host-guest complexes, nanoparticles, liposomes, nanoemulsion, microspheres, and hydrogels are beneficial to the exploitation of luteolin-based products. Moreover, some registered clinical trials on luteolin are being carried out, yet clinical research on anticancer effects should be continuously promoted.


Asunto(s)
Flavonas , Neoplasias , Humanos , Luteolina/farmacología , Luteolina/uso terapéutico , Preparaciones Farmacéuticas , Flavonas/farmacología , Flavonas/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Disponibilidad Biológica
20.
Nutr Cancer ; 76(1): 17-30, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37930032

RESUMEN

BACKGROUND: This study performed a meta-analysis to evaluate the combined effects of polyphenols and anti-programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) inhibitors. METHODS: Relevant studies were collected from electronic databases. Standardized mean differences (SMDs) or hazard ratio (HR) was calculated by Stata 15.0 software. RESULTS: Sixteen preclinical studies were included. The overall meta-analysis showed that, compared to anti-PD-1/PD-L1 alone, polyphenol combined therapy significantly reduced the tumor volume (SMD = -3.28), weight (SMD = -2.18), number (SMD = -2.17), and prolonged the survival (HR = 0.45) of mice (all P < 0.001). Pooled analysis of mechanism studies indicated polyphenol combined therapy could increase the number of cytotoxic CD8+ T cells (SMD = 3.88; P < 0.001), IFN-γ+ CD8+ T cells (SMD = 2.38; P < 0.001), decrease the number of myeloid-derived suppressor cells (SMD = -2.52; P = 0.044) and Treg cells (SMD = -4.00; P = 0.004) and suppress PD-L1 expression in tumors (SMD = -13.41; P < 0.001). Subgroup analyses demonstrated curcuminoids, flavonoids, and stilbene changed the tumor volume, the percentage of CD8+ T cells, IFN-γ+CD8+ T cells, and PD-L1 expression. CONCLUSION: Polyphenol supplementation may be a promising combined strategy for patients with poor response to anti-PD-1/PD-L1 monotherapy.


Asunto(s)
Antígeno B7-H1 , Neoplasias , Humanos , Animales , Ratones , Antígeno B7-H1/metabolismo , Inhibidores de Puntos de Control Inmunológico/metabolismo , Receptor de Muerte Celular Programada 1/metabolismo , Linfocitos T CD8-positivos , Polifenoles/farmacología , Polifenoles/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Suplementos Dietéticos
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