Induced Cell Apoptosis Research Articles

Lung cancer remains the leading cause of cancer-related mortality worldwide, highlighting the urgent need for the development of novel therapeutic agents. Glycyrrhiza glabra, a medicinally significant plant, is known for its rich composition of diverse phytochemicals. However, its role in the induction of apoptosis in lung cancer cells has not been well elucidated. The present study aimed to evaluate the apoptosis-associated cytotoxic and antiproliferative effects of Glycyrrhiza glabra methanol extract (GGME) on non-small cell lung cancer (A549) cells. The viability of GGME-treated A549 cells was assessed using an MTT assay, which revealed a significant antiproliferative effect at 200 µg/ml (p < 0.05). Morphological changes were observed via phase-contrast inverted microscopy. To elucidate the mode of cell death, Annexin V/PI staining was performed, and the mRNA levels of the pro-apoptotic Bax and anti-apoptotic Bcl-2 genes were quantified by real-time PCR. Interestingly, while Bax expression increased 4-fold (p < 0.01) compared to the control, Bcl-2 levels remained unchanged. Despite this pro-apoptotic shift in gene expression, the cells predominantly underwent necrotic cell death rather than apoptosis. Furthermore, LC-MS/MS analysis identified vanillic acid, fumaric acid, syringic acid, and thymoquinone as the major compounds in GGME. In conclusion, GGME exerts a antiproliferative effect primarily through necrosis rather than apoptosis.

Head and neck squamous cell carcinoma (HNSCC) remains a prevalent and aggressive malignancy, characterized by a lack of targeted therapies and limited clinical benefits. Here, we conducted an optimized whole-genome CRISPR screen across five HNSCC cell lines aimed at identifying actionable genetic vulnerabilities for rapid preclinical evaluation as novel targeted therapies. Given their critical role in cancer, cyclin-dependent kinases (CDKs) were prioritized for further investigation. Among these, CDK7 was identified as an essential and targetable gene across all five cell lines, prompting its selection for in-depth functional and molecular characterization. Genetic and pharmacological inhibition of CDK7 significantly and consistently reduced tumor cell proliferation due to generalized cell cycle arrest and apoptosis induction. Additionally, CDK7 knockout (KO) and selective inhibitors (YKL-5-124 and samuraciclib) demonstrated potent antitumor activity, effectively suppressing tumor growth in HNSCC patient-derived organoids (PDOs), as well as in both cell line- and patient-derived xenograft (PDX) mouse models with minimal toxicity. Mechanistically, CDK7 inhibition led to a broad downregulation of gene sets related to cell cycle progression and DNA repair, and significantly reduced the transcription of essential genes and untargetable vulnerabilities identified by our CRISPR screen. These findings highlight CDK7 as a promising therapeutic target for HNSCC. Our study provides strong evidence of the robust antitumor activity of CDK7-selective inhibition in disease-relevant preclinical models, strongly supporting its progression to clinical testing.

This review is devoted to research in the field of photodynamic and photothermal therapies for malignant tumors. Special attention in the review is given to photosensitizers based on compounds with a tetrapyrrole ring system, their metal complexes, BODIPY and aza-BODIPY derivatives, squaraines, and photoactivators based on metal complexes with other ligands such as phenanthroline and its derivatives, metronidazole, pyridine, and imidazole derivatives. Additionally, the review considers nanosized carriers for photosensitizers, such as organic and inorganic nanoparticles, liposomes, and extracellular vesicles. This review also discusses the dark toxicity and phototoxicity of these compounds and the processes of free oxygen radical formation, mitochondrial dysfunction, and induction of apoptosis in cancer cells. It has been established that nanoscale delivery systems are more promising for use in photodynamic and photothermal therapy compared to molecular photosensitizers. This is due to their improved solubility in physiological environments, selective accumulation in tumors, prolonged photoactivity, and lower therapeutic dose, which allows for the minimization of the side effects of treatment. Among the molecular photosensitizers under consideration, amphiphilic tetrapyrroles appear to be the most promising. Specifically, tetrapyrrole complexes of indium (III) and iridium (III) with non-porphyrin ligands exhibit favorable photophysical and biological characteristics. The review also indicates that photosensitizers tend to localize in the mitochondria of tumor cells, contributing to oxidative stress and apoptosis activation. This review may be of interest to biochemists and oncologists.

BackgroundHuangqi Fuling Decoction (HQFLT) is a traditional Chinese medicine prescription that is applied to treat a variety of diseases. However, the mechanism of HQFLT in the treatment of gastric cancer is still unclear, which hinders its clinical application.MethodsComponents and targets of HQFLT were collected from TCMSP, TCMID and ETCM databases, and potential targets of gastric cancer were collected from GEO database. The intersection targets of component disease were imported into STRING database to construct protein–protein interaction network, and the intersection targets were analyzed by GO and KEGG to explore the involved biological processes. The network topology analysis of intersection targets was carried out using Cytoscape software, and hub genes were selected according to the degree value. To further identify the main active components of HQFLT, we used UPLC-MS/MS techniques for analysis and intersected with network pharmacological results to obtain the most critical components. Molecular docking techniques were used to calculate the binding energy of intersection components and hub genes. Regarding cell experiments, the effect of HQFLT on the viability of gastric cancer cells was detected by CCK-8 assay, and the effect of HQFLT on cell proliferation was verified by flow cytometry and colony formation assay. The transwell experiment was conducted to investigate the effect of HQFLT on tumor metastasis. qRT-PCR and Western blot were used to detect the regulatory effects of HQFLT on hub genes and key signaling pathways.ResultsA total of 189 active components, and 278 targets of HQFLT and 1817 targets of gastric cancer were obtained by network pharmacology. A total of 51 intersection targets were screened by Venny method. These targets were mainly involved in signal transduction, apoptosis regulation and angiogenesis, and may be involved in the regulation of MAPK signaling pathway. A total of 5 hub genes were obtained after degree screening by Cytoscape, namely IL6, PTGS2, ICAM1, VCAMI and CCL2, which showed significant differences in clinical staging, molecular typing and survival prognosis. After the intersection of 44 components obtained from UPLC-MS and network pharmacology, Calycosin was obtained. The results of molecular docking showed that the compound had strong binding ability with hub genes. Regarding cell experiments, HQFLT had the ability to inhibit proliferation, block cell cycle, induce cell apoptosis, inhibit colony formation, and inhibit migration and invasion of gastric cancer cells. qRT-PCR and Western blot experiments confirmed that HQFLT could down-regulate the expression of hub genes and inhibit the activation of RAS-MER-ERK signaling pathway.ConclusionHQFLT inhibited the proliferation and metastasis of gastric cancer. The mechanism may involve the regulation of the RAS-MEK-ERK signaling pathway, with ICAM1 and VCAM1 being potential targets for targeted therapy.Graphical Supplementary InformationThe online version contains supplementary material available at 10.1186/s12906-025-05111-6.

POU2F1 facilitates the malignant phenotypes and aerobic glycolysis of pituitary adenoma by activating LDHA transcription.

Phenolic zingerone nanoparticles impede cell cycle progression to compete against human urothelial carcinoma.

Effects of CdTe quantum dot exposure on the calcium signaling pathway in rat dorsal root ganglion cells ND7/23.

USF2 regulates the JAK2/STAT3 pathway through PEX3-mediated SLC25A17 upregulation to affect lipid metabolism and promote the progression of lung adenocarcinoma.

Caulerpin suppresses tumor-associated angiogenesis and tumor growth via Hippo signaling in cervical cancer.

Discovery of novel thiourea benzenesulfonamides based 1,8-naphthalimide derivatives as carbonic anhydrase IX inhibitors that induce ferroptosis and inhibit triple-negative breast cancer metastasis.

Mechanisms underlying the therapeutic effects of Amygdalin in treating Cervical Cancer based on multi-omics analysis.

TMEFF2 promotes hyperplastic prostate progression by degrading BAX via TRIM17.

Discovery of novel covalent PI3Kδ inhibitors bearing alaninamide moiety by lysine-targeted covalent strategy.

pH-responsive chitosan-sodium alginate nanocarriers for curcumin delivery against brain cancer.

In vitro cultured biomass of Rindera graeca, a rare endemic plant, is an efficient renewable source of bioactive naphthoquinones, e.g., rinderol, a potential bioactive inducer of apoptosis in cancer cells. Bioengineering strategies, as biomass immobilization on functionalized biomaterial-based scaffolds, elicitation by chitosan, and in situ extraction of metabolites, are tested for intensifying naphthoquinones production in R. graeca hairy roots. The aim of the study was to investigate the effects of hybrid poly(lactic)–chitosan scaffolds on biomass proliferation and rinderol production in R. graeca hairy roots. Effects of chitosan origin (fungal or squid), molecular mass (350–1800 kDa), and concentration (up to 45%) in the developed hybrid scaffolds have been quantitatively identified, and the results were compared to the reference culture system containing an unmodified PLA-based construct. Applying PLA–chitosan scaffold containing 33% of fungal chitosan resulted in 635 times higher rinderol production (3660 µg gDW−1) than the application of reference scaffolds. Among the tested parameters, the chitosan concentration in the hybrid scaffolds revealed significant importance in rinderol production. To sum up, the developed hybrid PLA-chitosan scaffold may be recognized as a functional key element supporting the production of naphthoquinones in cultures of R. graeca biomass.

Licoricidin suppresses growth and metastasis of hepatocellular carcinoma by targeting PI3K/AKT signaling.

Efficient composite partnering of crab shell-derived chitosan with tin oxide for anticancer and other biomedical applications.

Lysosome-Associated Membrane Protein Type 2A (LAMP2A) serves as the critical rate-limiting component of chaperone-mediated autophagy (CMA), governing substrate translocation into lysosomes. Accumulating studies indicate that LAMP2A downregulation leads to CMA impairment in multiple cancer malignancies. In this study, we found that LAMP2A is significantly upregulated in head and neck squamous cell carcinoma (HNSCC) compared to normal tissues. Cell functional studies performed on FaDu and CAL-27 cells showed that downregulation of LAMP2A inhibited cell proliferation and stemness, and induced cell apoptosis. Since CMA specifically targets proteins containing a pentapeptide motif (KFERQ-like motif) in a LAMP2A-dependent manner, we further employed an integrated proteomic-interactomic approach combined with KFERQ motif analysis. This comprehensive strategy identified Selenium Binding Protein 1 (SELENBP1) as a novel putative CMA substrate in HNSCC. Subsequent validation confirmed that knockdown of CMA receptor LAMP2A significantly increased SELENBP1 protein levels both in vitro and in vivo. CO-IP assays confirmed that SELENBP1 interacts with the CMA chaperone protein heat shock cognate 71 kDa protein (HSPA8) in a KFERQ motif ("EKVIQ")-dependent manner. Overexpression of SELENBP1 attenuated HNSCC cell proliferation and viability. Most importantly, silencing of SELENBP1 partially rescued the tumor-suppressive phenotypes induced by LAMP2A knockdown, suggesting that SELENBP1 mediated the effects of LAMP2A knockdown on HNSCC. This study provides insights into the role of the LAMP2A-CMA-SELENBP1 axis in the development of novel therapies for HNSCC. Implications: This study provides a novel insight into the role of CMA during the pathogenesis of HNSCC.

Immune checkpoint combination therapy, particularly dual LAG-3/PD-1 blockade, demonstrates superior clinical efficacy over monotherapy in cancers like melanoma, yet its mechanistic synergy requires further validation. In this study, we established a cell co-culture model by co-culturing LAG-3+PD-1+ Jurkat cells induced by phytohemagglutinin (PHA) and human tumor cells with high expression of LAG-3 and PD-1 major ligands to characterize the combination effect of LBL-007 with anti-PD-1 antibodies and the mechanism of action in cancer immunotherapy. The results showed that the combination of LBL-007 and anti-PD-1 antibodies in the cell co-culture model enhanced the ability of activated Jurkat cells to kill tumor cells compared with monotherapy. Furthermore, this combination also inhibited the apoptosis of Jurkat cells and promoted IL-2, IL-10, and TNF secretion from Jurkat cells. Tumor cell death via apoptosis induced by activated Jurkat cells was observed, which was enhanced by combined LBL-007 and anti-PD-1 antibody treatment. The combination of LBL-007 and anti-PD-1 antibodies delayed tumor growth and promoted tumor cell apoptosis compared with monotherapy in human LAG-3 transgenic mice subjected to transplantation with colorectal tumor cells. Taken together, the combination of LBL-007 and anti-PD-1 antibodies plays an enhanced antitumor role by improving T cell viability and activity as well as by promoting T cell-induced apoptosis, thereby suggesting this combination as a potential effective strategy for cancer immunotherapy.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-21400-z.

While lung cancer remains a lethal disease despite treatment advances, some parasitic infections can demonstrate cancer-modulating roles and exhibit anti-tumor effects. The emergence of hydatid cysts as a potential anti-cancer treatment has sparked optimism for the development of more successful therapies. This research examines the effect of hydatic cysts on the growth and proliferation of lung tumor cells, as well as the underlying molecular mechanisms involved. The laminated layer (LL) of the hydatid cyst antigens was administered to lung cancer cells with varying dosages and durations. The MTT assay was applied to evaluate cell viability. After exposure to different concentrations of LL antigens, the apoptosis, necrosis, cell cycle, and intracellular reactive oxygen species (ROS) of the cell culture were measured using flow cytometry. The expression levels of SOX-9, β-catenin, CD133, and CD44 genes were assessed using Real-Time PCR. Treating A549 cells with varying concentrations of LL antigens resulted in a decrease in viable cells, which depended on both time and dosage. Treatment with cysts led to apoptosis induction and a reduction in necrosis percentage in a dose-dependent manner. The induction of apoptosis correlated with elevated ROS production and a notable decrease in the expression of invasion-related genes (β-catenin, CD133, and CD44) (P < 0.05). However, this reduction in expression was not statistically significant for SOX-9. Exposing lung cancer cells to precise amounts of crude LL antigens resulted in cell death, apoptosis, increased intracellular ROS levels, and reduced expression of genes linked to cancer cell growth and invasion. These results lay the groundwork for further exploring purified Echinococcus granulosus parasite antigens as potential drug targets in cancer treatment.