Cell death pathways: molecular mechanisms and therapeutic targets for cancer

MedComm, Journal Year: 2024, Volume and Issue: 5(9)

Published: Sept. 1, 2024

Abstract Cell death regulation is essential for tissue homeostasis and its dysregulation often underlies cancer development. Understanding the different pathways of cell can provide novel therapeutic strategies battling cancer. This review explores several key mechanisms apoptosis, necroptosis, autophagic death, ferroptosis, pyroptosis. The research gap addressed involves a thorough analysis how these be precisely targeted therapy, considering tumor heterogeneity adaptation. It delves into genetic epigenetic factors signaling cascades like phosphatidylinositol 3‐kinase/protein kinase B/mammalian target rapamycin (PI3K/AKT/mTOR) mitogen‐activated protein kinase/extracellular signal‐regulated (MAPK/ERK) pathways, which are critical death. Additionally, interaction microenvironment with cells, particularly influence hypoxia, nutrient deprivation, immune cellular interactions, explored. Emphasizing strategies, this highlights emerging modulators inducers such as B lymphoma 2 (BCL2) homology domain 3 (BH3) mimetics, tumour necrosis factor‐related apoptosis‐inducing ligand (TRAIL), chloroquine, innovative approaches to induce ferroptosis provides insights therapy's future direction, focusing on multifaceted circumvent drug resistance. examination evolving underlines considerable clinical potential continuous necessity in‐depth exploration within scientific domain.

Language: Английский

---

The molecular code of kidney cancer: A path of discovery for gene mutation and precision therapy

Molecular Aspects of Medicine, Journal Year: 2025, Volume and Issue: 101, P. 101335 - 101335

Published: Jan. 1, 2025

Renal cell carcinoma (RCC) is a malignant tumor with highly heterogeneous and complex molecular mechanisms. Through systematic analysis of TCGA, COSMIC other databases, 24 mutated genes closely related to RCC were screened, including VHL, PBRM1, BAP1 SETD2, which play key roles in signaling pathway transduction, chromatin remodeling DNA repair. The PI3K/AKT/mTOR particularly important the pathogenesis RCC. Mutations such as PIK3CA, MTOR PTEN are associated metabolic abnormalities proliferation. Clinically, mTOR inhibitors VEGF-targeted drugs have shown significant efficacy personalized therapy. Abnormal regulation reprogramming, especially glycolysis glutamine pathways, provides cells continuous energy supply survival advantages, GLS1 promising results preclinical studies. This paper also explores potential immune checkpoint combination targeted drugs, well application nanotechnology drug delivery In addition, unique mechanisms revealed individualized therapeutic strategies explored for specific subtypes TFE3, TFEB rearrangement type SDHB mutant type. review summarizes common gene mutations their mechanisms, emphasizes diagnosis, treatment prognosis, looks forward prospects multi-pathway therapy, immunotherapy treatment, providing theoretical support clinical guidance new development.

Language: Английский

---

Ellagic Acid and Cancer Hallmarks: Insights from Experimental Evidence

Biomolecules, Journal Year: 2023, Volume and Issue: 13(11), P. 1653 - 1653

Published: Nov. 15, 2023

Cancer is a complex and multifaceted disease with high global incidence mortality rate. Although cancer therapy has evolved significantly over the years, numerous challenges persist on path to effectively combating this disease. Natural compounds derived from plants, fungi, or marine organisms have garnered considerable attention as potential therapeutic agents in field of research. Ellagic acid (EA), natural polyphenolic compound found various fruits nuts, emerged prevention treatment agent. This review summarizes experimental evidence supporting role EA targeting key hallmarks cancer, including proliferation, angiogenesis, apoptosis evasion, immune inflammation, genomic instability, more. We discuss molecular mechanisms by which modulates signaling pathways targets involved these hallmarks, based vitro vivo studies. The actions make it promising candidate for therapy. Understanding its impact biology can pave way developing novel strategies combat

Language: Английский

---

Extraction of coronary thrombus-derived exosomes from patients with acute myocardial infarction and its effect on the function of adventitial cells

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(1), P. e0313582 - e0313582

Published: Jan. 16, 2025

Background Type I acute myocardial infarction (T1MI) has a very high morbidity and mortality rate. The role of thrombus-derived exosomes (TEs) in T1MI is unclear. Methods objective this study was to identify the optimal thrombolytic drug concentration for extracting TEs. To end, series time combinations were tested. Subsequently, effect TEs on thrombus-adjacent cells investigated. Finally, we conducted lncRNA microarray analysis extracted (GSE213115). Results been demonstrated promote necrosis, autophagy, ferroptosis human cardiomyocytes, while inhibiting proliferation migration umbilical vein endothelial (HUVECs). Furthermore, can stimulate smooth muscle cells, induce transformation from contractile secretory phenotype. Bioinformatics revealed that five lncRNAs, AC068418.2, AC010186.3, AL031430.1, AC121333.1, AL136526.1, exhibited significant differential expression TE regulated cell autophagy by directly binding TP53, TP63, RELA, respectively. Conclusions We demonstrate as potential target research direction treatment heart failure after T1MI. may regulate through enrichment certain lncRNAs.

Language: Английский

---

Changing the Landscape of Solid Tumor Therapy from Apoptosis-Promoting to Apoptosis-Inhibiting Strategies

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(6), P. 5379 - 5396

Published: May 28, 2024

The many limitations of implementing anticancer strategies under the term “precision oncology” have been extensively discussed. While some authors propose promising future directions, others are less optimistic and use phrases such as illusion, hype, false hypotheses. reality is revealed by practicing clinicians cancer patients in various online publications, one which has stated that “in quest for next cure, few researchers bother to look back at graveyard failed medicines figure out what went wrong”. message clear: Novel therapeutic with catchy names (e.g., synthetic “lethality”) not fulfilled their promises despite decades extensive research clinical trials. main purpose this review discuss key challenges solid tumor therapy surprisingly continue be overlooked Nomenclature Committee on Cell Death (NCCD) numerous other authors. These include: impact chemotherapy-induced genome chaos multinucleation) resistance relapse, oncogenic function caspase 3, cell anastasis (recovery from late stages apoptosis), pitfalls ubiquitously used preclinical chemosensitivity assays “viability” growth delay studies live animals) score pro-survival responses “lethal” events. outlined herein underscore need new directions management tumors.

Language: Английский

---

Utilizing network p harmacology to investigate the probable mechanism of Danshen chuanxiong drug pair in Kawasaki disease

Tropical Journal of Pharmaceutical Research, Journal Year: 2025, Volume and Issue: 23(12), P. 2001 - 2015

Published: Jan. 17, 2025

Purpose: To investigate the primary components and effect of Danshen-Chuanxiong (DS-CX) in treatment Kawasaki disease. Methods: Active ingredients DS-CX targets action were screened via Traditional Chinese Medicine Systematic Pharmacology (TCMSP) SwissTargetPrediction databases. Targets disease queried OMIM, GeneCards, DRUGBANK, Disgenet databases, intersected with drug targets. Protein-protein interaction maps (PPIs) constructed using STRING database Cytoscape software, core genes screened. Pathway enrichment analyses (DAVID database, Gene Ontology (GO) function Kyoto Encyclopedia Genes Genomes (KEGG)) conducted for targeting crossover Results: A total 64 active corresponding potential target obtained. Also, 928 human related to obtained from GeneCards Potential was disease-related genes, a 55 The PPI network built Cyotoscape overlapping further 61 their effects on GO-function analysis revealed that affected by positively regulating gene expression. KEGG found mainly enriched pathways involved cancer. Conclusion: regulates (AKT1, IL6, TP53) other through which turn act cancer pathway. Thus, demonstrates anti-inflammatory anti-platelet activities helps blood vessel repair remodeling Further studies validate Danshen Chuanxiong are needed determine its mechanism action.

Language: Английский

---

HDAC inhibitor regulates the tumor immune microenvironment via pyroptosis in triple negative breast cancer

Molecular Carcinogenesis, Journal Year: 2024, Volume and Issue: 63(9), P. 1800 - 1813

Published: June 11, 2024

Abstract Pyroptosis, an inflammatory form of cell death, promotes the release immunogenic substances and stimulates immune recruitment, a process, which could turn cold tumors into hot ones. Thus, instigating pyroptosis in triple‐negative breast cancer (TNBC) serves as viable method for restoring antitumor immunity. We analyzed effects Histone Deacetylase Inhibitors (HDACi) on TNBC cells using Cell Counting Kit‐8 colony formation assay. Apoptosis lactate dehydrogenase (LDH) assays were utilized to determine death. The pyroptotic executor was validated by quantitative real‐time polymerase chain reaction western blot. Transcriptome investigate pyroptosis‐inducing mechanisms. A subcutaneously transplanted tumor model generated BALB/c mice evaluate infiltration cells. HDACi significantly diminished proliferation, “balloon”‐like became apparent. led intra extracellular material exchange, signified LDH uptake propidium iodide. Among gasdermin family, expressed maximum quantities GSDME, expression GSDMA, GSDMB, GSDME augmented post treatment. Pyroptosis instigated via activation caspase 3‐GSDME pathway with potential mechanisms being cycle arrest altered intracellular REDOX balance due aberrant glutathione metabolism. In vivo experiments demonstrated that can activate pyroptosis, limit growth, escalate CD8+ lymphocyte CD11b+ along increased presence granzyme B tumors. instigate TNBC, promoting consequently intensifying efficacy anticancer

Language: Английский

---

Role of intrinsic apoptosis in environmental exposure health outcomes

Trends in Molecular Medicine, Journal Year: 2023, Volume and Issue: 30(1), P. 56 - 73

Published: Dec. 5, 2023

Language: Английский

---

The regulatory effects of p53 on the typical and atypical ferroptosis in the pathogenesis of osteosarcoma: A systematic review

Frontiers in Genetics, Journal Year: 2023, Volume and Issue: 14

Published: March 29, 2023

Study background: As a rare condition, osteosarcoma affects approximately 3% of all cancer patients. Its exact pathogenesis remains largely unclear. The role p53 in up- and down-regulating atypical typical ferroptosis primary objective the present study is investigating regulating osteosarcoma. Methods: Preferred Reporting Items for Systematic Reviews Meta-Analysis (PRISMA) Patient, Intervention, Comparison, Outcome, Studies (PICOS) protocol were used initial search. literature search was performed six electronic databases, including EMBASE, Cochrane library trials, Web Science, PubMed, Google Scholar, Scopus Review, using keywords connected by Boolean operators. We focused on studies that adequately defined patient profiles described PICOS. Results discussion: found played fundamental down-regulatory roles ferroptosis, resulting either advancement or suppression tumorigenesis, respectively. Direct indirect activation inactivation downregulated its regulatory Enhanced tumorigenesis attributed to expression genes associated with development. Modulation target protein interactions, especially SLC7A11, resulted enhanced tumorigenesis. Conclusion: Typical functions p53. MDM2 inactivated p53, leading downregulation whereas upregulated ferroptosis. Further should be unmask possible clinical applications management

Language: Английский

---

Silencing of FAM111B inhibits tumor growth and promotes apoptosis by decreasing AKT activity in ovarian cancer

Experimental Biology and Medicine, Journal Year: 2023, Volume and Issue: 248(12), P. 1043 - 1055

Published: April 24, 2023

Ovarian cancer is the most lethal gynecological tumor in women worldwide. FAM111B (family with sequence similarity 111 member B) an oncoprotein associated multiple cancers, but its biological functions ovarian remain elusive. In this study, was overexpressed tissues and cell lines. Functional studies vitro revealed that silencing of inhibited proliferation, invasion, migration, as well increased apoptosis. Furthermore, arrested cycle at G1/S phase. western blot assays demonstrated resulted downregulation phospho-AKT (p-AKT) protein expression, upregulation p53 caspase-1 expression. The xenograft animal model growth, enhanced apoptosis, Ki-67 proliferating nuclear antigen (PCNA) expression vivo. Conversely, overexpression exhibited opposite effects on xenograft. It previously established inactivating AKT progression. This study found inhibits growth promotes apoptosis by decreasing activity cancer. Caspase-1 signaling also influenced function SKOV3 cells. Collectively, our results demonstrate a potential therapeutic strategy against

Language: Английский

---