Induced Cell Apoptosis Research Articles

Luteolin inhibits proliferation of lung cancer A549 cells by increasing ROS production and inhibiting the AKT/mTOR signaling pathway and HO-1 expression

To investigate the mechanism of luteolin for inhibiting proliferation of lung cancer A549 cells. A549 cells treated with different concentrations of luteolin for 48 h were evaluated for changes in cell viability, proliferation, reactive oxygen species (ROS) production and apoptosis using MTT assay, plate cloning assay, EdU staining, DCFH-DA assay and Hoechst33258 staining. The changes in cell autophagy were examined with MDC staining, and the expressions of apoptosis-related proteins (Bax, Bcl-2, and cleaved caspase-9), autophagy-related proteins (LC3B, Beclin 1, and P62), AKT/mTOR pathway proteins, and HO-1 protein were detected using Western blotting. Treatment with luteolin dose-dependently inhibited the viability and proliferation of A549 cells, increased intracellular ROS levels, up-regulated the expressions of Bax, cleaved caspase-9, and Beclin 1, increased the LC3B-II/LC3B-I ratio, down-regulated the expressions of Bcl-2 and P62, and induced cell apoptosis and autophagy. Luteolin also significantly inhibited the phosphorylation of AKT and mTOR and down-regulated the expression of HO-1 protein in the cells. Luteolin induces apoptosis and autophagy to inhibit proliferation of A549 cells by increasing ROS production, inhibiting the AKT/mTOR pathway and down-regulating HO-1 protein expression.

Shikonin induces the apoptosis and pyroptosis of EGFR-T790M-mutant drug-resistant non-small cell lung cancer cells via the degradation of cyclooxygenase-2

BackgroundThe T790M mutation in the epidermal growth factor receptor (EGFR) gene is the primary cause of resistance to EGFR-tyrosine kinase inhibitor (TKI) therapy in non-small cell lung cancer (NSCLC) patients. Previous research demonstrated that certain traditional Chinese medicine (TCM) monomers exhibit anti-tumor effects against various malignancies. This study aims to investigate the potentials of shikonin screened from a TCM monomer library containing 1060 monomers in killing EGFR-T790M drug-resistant NSCLC cells and elucidate the underlying mechanisms.MethodsMTT method was used to screen for the TCM monomers with significant killing effects on H1975 cells carrying the EGFR-T790M mutation. The influences of the identified monomer shikonin on cell growth were determined by the colony formation assay. Annexin-V/PI staining and JC-1 staining were applied to detect the effects of shikonin on cell apoptosis. The influences of shikonin on cell membrane integrity were detected by lactate dehydrogenase (LDH) release assay. Reactive oxygen species (ROS) generation was analyzed using DCFH-DA as probe. The mechanisms of shikonin affecting the stability of cyclooxygenase-2 (COX-2) were evaluated by using specific inhibitors for protein degradation pathways. Western blotting was performed to assess the effects of the alteration of COX-2 expression or enzymatic activity on the related signal pathways as well as the apoptotic and pyroptotic markers.ResultsShikonin was identified as a potent cytotoxic compound against EGFR-T790M-mutant NSCLC cells. Shikonin induced cell apoptosis and pyroptosis by triggering the activation of the caspase cascade and cleavage of poly (ADP-ribose) polymerase and gasdermin E by elevating intracellular ROS levels. Further investigations revealed that shikonin induced the degradation of COX-2 via the proteasome pathway, thereby decreasing COX-2 protein level and enzymatic activity and subsequently inhibiting the downstream PDK1/Akt and Erk1/2 signaling pathways through the induction of ROS production. Notably, COX-2 overexpression attenuated shikonin-induced apoptosis and pyroptosis, whereas COX-2 inhibition with celecoxib enhanced the cytotoxic effects of shikonin.ConclusionsCombination treatment with shikonin and COX-2 inhibitor may be a suitable therapeutic strategy for EGFR-T790M-mutant NSCLC treatment.

USP33 Regulates DNA Damage Response and Carcinogenesis Through Deubiquitylating and Stabilising p53.

The de-ubiquitinase USP33 has been shown to possess either tumour-promoting or inhibitory effect on human cancer cells. However, all these findings are mainly based on invitro cell culture models, and the invivo evidence, which is more plausible to digest the functional role of USP33 in carcinogenic process, is still lacking. Here, we demonstrate that USP33 modulates DNA damage responses including cell cycle arrest and apoptosis induction through associating with p53. It directly interacts with p53 to mediate its de-ubiquitination and further stabilisation under DNA damage condition. Depletion of USP33 induces an enhanced level of p53 ubiquitination, which de-stabilises p53 protein leading to impaired DNA damage responses. Furthermore, USP33 silencing shows either promoted or inhibited effect on cell proliferation in human cancer cells with p53 WT and mutant background, respectively. Consistently, mice with hepatocyte-specific USP33 knockout are more sensitive to nitrosodiethylamine (DEN)-induced hepatocarcinogenesis compared to wild type mice. Thus, our invitro and invivo evidences illustrate that USP33 possesses anti-tumour activity via regulating p53 stability and activity.

Modulation of signature cancer-related genes in oral cancer cells (Ca9-22) by anethole treatment: Insights into therapeutic potential.

To explore an alternative strategy to chemotherapy to combat oral cancer, natural products and their derivates constitute one promising approach. In the last previous study, we have demonstrated the potential anti-tumor properties of anethole; an aromatic compound abundantly present in nature that serves as a major active ingredient found in plants like anise and fennel. In the current study, we aimed to investigate how this molecule inhibits oral cancer cell proliferation and induces apoptosis. This will be carried out by a transcriptomic study of its effects on the expression profile of cell cycle and apoptosis regulation genes in gingival cancer cells. cell cycle. Ca9-22 cells were treated with 10 μM of anethole (IC50) and cell proliferation was evaluated by MTT assay. The percentage of cells in different stages of the cell cycle was measured by flow cytometry. Cytotoxicity was evaluated by LDH assay and apoptosis was investigated by Pi/Annexin V assay following 24-hour treatment. Furthermore, we employed PCR array analysis to investigate alterations in the expression levels of oncogenes and tumor suppressor genes associated with cell cycle regulation and apoptosis. Finally, Gene-gene interactions were examined using the Gene MANIA database. Our findings demonstrate that anethole significantly attenuated the proliferation of Ca9-22 cells, leading to disturbances in cell cycle progression and eliciting cellular toxicity and apoptosis. By a double normalizing with two housekeeping genes (Actin and GAPDH), we show that, treatment with 10 μM of anethole alters (more than two-fold) the expression of 13 genes involved in the control of the cell cycle (8 were up regulated and 5 were down regulated) and 7 genes involved in the regulation of apoptosis (4 were up regulated and 3 downregulated by anethole). Finally, each group of genes modulated by anethole forms a network of connections between them or with other genes. Our study suggests that anethole holds promise as a potential alternative treatment for oral cancer by its ability to modify numerous oncogenes and tumor suppressor genes implicated in the cell cycle regulation and induction of apoptosis in oral cancer cells. These findings underscore the significance of further research into the potential therapeutic application of anethole as an alternative drug for managing oral cancer.

Curcumin: Epigenetic Modulation and Tumor Immunity in Antitumor Therapy.

Curcumin is the main ingredient of the Chinese herbal turmeric rhizome, used to treat tumors, diabetes, inflammation, neurodegenerative diseases, cardiovascular diseases, metabolic syndrome, and liver diseases. The antitumor effects of curcumin have received even more attention. One of the main mechanisms of antitumor effects includes inhibition of tumor invasion and migration, induction of tumor cell apoptosis, and inhibition of various cell signaling pathways. It has been found that the antitumor biological activity of curcumin in the body is associated with epigenetic mechanisms. That also implies that curcumin may act as a potential epigenetic modulator to influence the development of tumor diseases. The immune system plays an essential role in the development of tumorigenesis. Tumor immunotherapy is currently one of the most promising research directions in the field of tumor therapy. Curcumin has been found to have significant regulatory effects on tumor immunity and is expected to be a novel adjuvant for tumor immunity. This paper summarizes the antitumor effects of curcumin from four aspects: molecular and epigenetic mechanisms of curcumin against a tumor, mechanisms of curcumin modulation of tumor immunotherapy, reversal of chemotherapy resistance, and novel drug delivery system of curcumin, which provide new directions for the development of new antitumor drugs.

Evaluation of Chelidonium Majus L. Alkaloid Effect on VEGF Gene Expression and Cell Apoptosis in the Burkitt Lymphoma Cell Line

Background: Burkitt lymphoma (BL) is a type of mature B-cell non-Hodgkin’s lymphoma that commonly develops in children and young adults. Vascular endothelial growth factor (VEGF) is acknowledged as a vital regulator of angiogenesis in both normal and disease states. In light of the adverse effects linked to chemical treatments, this study aimed to explore the anticancer effects of Chelidonium majus L. alkaloid on the Daudi BL cell line and to evaluate the expression of the VEGF gene. Materials and Methods: This project was an experimental study. The cytotoxic effects of the alkaloid derived from Chelidonium majus L. on the Daudi and normal cells were evaluated using MTT assays (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide). The induction of apoptosis in cells was measured utilizing Annexin V/propidium iodide (PI) flow cytometry. Additionally, the expression levels of the VEGF gene were determined via a Real-time PCR assay. Data were entered into SPSS, version 21. Student’s t-test and ANOVA test were used for comparisons of groups. Results: The 50% cytotoxic concentration (CC50) of the alkaloid from Chelidonium majus L. was found to be 56.35µg/mL in the Daudi cell. Findings from flow cytometry aligned with those from MTT assays. Real-time PCR assay results showed a significant decrease in the VEGF gene expression (P<0.009). Effects observed after 48 hours of treatment across various concentrations of Chelidonium majus L. alkaloid demonstrated dose-dependency. However, in peripheral blood mononuclear cells (PBMCs) as a control, the alkaloid did not significantly affect the expression of the VEGF gene (P>0.05). Conclusion: The alkaloid is derived from Chelidonium majusL. Appears to influence angiogenesis by down-regulating the VEGF gene expression, suggesting its potential as a complementary agent in chemotherapy for Burkitt lymphoma. However; further research is required to evaluate the effectiveness of the Chelidonium majusL. Extract as a definitive treatment for Burkitt lymphoma.

Discovery of a Novel Co-crystal of Chrysin and Oroxylin a with Anticancer Properties from Leaves of Oroxylum indicum.

As the number of new cancer cases increases every year, there is a necessity to develop new drugs for the treatment of different types of cancers. Plants' resources are considered to be huge reservoirs for therapeutic agents in nature. Among all the medicinal plants, Oroxylum indicum is one of the most widely used medicinal plants in India, China, and Southeast Asian countries. Combinatorial drug treatment, on the other hand, is favored over single drug treatment in order to target multiple biomolecular moieties that help in the growth and development of cancer. Therefore, combinatorial drug treatment using a co-crystal of multiple drugs gives researchers an idea of the development of a new type of drug for targeting multiple targets. In this study, a new co-crystal of chrysin and oroxylin A was isolated from the leaves of O. indicum, and its anticancer properties were studied in cervical cancer cells HeLa. This study was conducted with the aim of identifying new anticancer compounds from the leaves of Oroxylum indicum and studying the anticancer properties of the isolated compound. In this study, we elucidated the structure of a new co-crystal compound, which was isolated from the leaf extract of Oroxylum indicum. The apoptosis induction mechanism of the newly discovered co-crystal in HeLa cells was also studied. A crystal compound from the chloroform extract of leaves of Oroxylum Indicum was isolated by solvent fractionation and chromatographic methods involving HPLC. The molecular structure of the isolated crystal was elucidated by Single Crystal-XRD, FT-IR analysis, and further determined by LC-MS. The antiproliferative activity was carried out using an MTT assay and fluorescence microscopy, and the mechanism of apoptosis was determined using Western blotting techniques. The novel co-crystal consists of two active pharmaceutical ingredients (APIs) in a 1:1 ratio, i.e., oroxylin A and chrysin. The isolated new co-crystal induced death in HeLa cells with a very low IC50 value of 8.49μM. It induced caspase-dependent apoptosis in HeLa cells by activation of Caspase-3 through inhibition of ERKs and activation of p38 of MAPK cell signalling pathway. This study presents the first report on the discovery of a naturally occurring co-crystal of chrysin and oroxylin A and the involvement of ERKs and p38 of MAPK pathways in the induction of apoptosis in HeLa cells by the co-crystal. Our study sheds light on the development of a co-crystal of chrysin and oroxylin A in a specific ratio of 1:1 for combination therapy of the two APIs. The purified co-crystal was found to be more efficient compared to the compounds present individually. Further analysis of the physiochemical properties and molecular mechanisms of the isolated co-crystal in different cancer cells is warranted for its application in therapeutics.

Combination of chemotherapy and c-MET inhibitors has synergistic effects in c-MET overexpressing pancreatic cancer cells.

Pancreatic ductal adenocarcinoma (PDAC) remains as one of the most lethal malignancies. c-MET is an important oncogenic kinase involved in PDAC progression. We determined the anticancer effect of c-MET inhibitors, crizotinib and cabozantinib, combined with chemotherapeutic agents, doxorubicin, oxaliplatin and gemcitabine, against different PDAC and a lung adenocarcinoma cell line expressing different levels of c-MET. MTT assay was performed to assess cell growth inhibition. Synergistic combinations were evaluated in spheroid cultures, while apoptosis was determined through Hoechst33258 staining. The effect of drug combinations on cell cycle and apoptosis induction was examined by RNase/PI flow cytometric assay. We also evaluated reactive oxygen species (ROS) levels using 2',7'-dichlorofluorescein-diacetate (DCFH-DA) assay to explore the possible mechanisms contributing to synergism. Combination of crizotinib or cabozantinib with doxorubicin exhibited synergistic effects in c-MET overexpressing cells. Conversely, combinations of c-MET inhibitors with other agents were additive or even antagonistic. Combination index (CI) values calculated with Calcusyn software were 0.631-0.730 for crizotinib and 0.542-0.746 for cabozantinib co-administrations. Synergistic combinations showed significant spheroid growth inhibition and apoptosis induction in Suit-2, c-MET dependent PDAC cells. These combinations also significantly increased the number of cells in both apoptotic sub-G1 phase and the G2/M phase compared to single-drug treatment. Increased ROS production seemed to be a possible mechanism underlying synergism. In conclusion, c-MET inhibitors synergize with DNA damaging agent, doxorubicin, in cancer cells with c-MET overexpression, indicating that these combination therapies may be a promising cancer therapeutic strategy.

M1 macrophage-derived exosomes alleviate leukemia by causing mitochondrial dysfunction.

Acute myeloid leukemia (AML) is one type of blood cancer that initially has a high cure rate but frequently relapses and leading to death. Therefore, there is an urgent need for innovative AML treatments. The leukemia C1498 cells were co-cultured with M1 macrophage-derived exosomes (M1-exo), and the proliferation and apoptosis of C1498 cells were investigated using CCK-8 and flow cytometry, respectively. qPCR and Western blot were applied to determine the PGAM5 expression in M1-exo treated C1498 cells. The role of M1-exo-derived PGAM5 in mitochondria was examined via fluorescence staining. The anti-inflammatory effects of M1-exo-derived PGAM5 and M1-exo were evaluated by flow cytometry, HE staining, and immunohistochemistry in xenograft and nude mouse tumorigenic models. M1-exo exhibited a potent capability to attenuate C1498 cell proliferation, and induce cell apoptosis. In vivo experimentation demonstrated that administration of M1-exo led to a reduction in leukocyte count, alleviated inflammatory infiltration, decreased liver and spleen weights, and significantly diminished tumor size. PGAM5 was elevated in M1-exo, and knockdown of PGAM5 in C1498 cells and M1-exo enhanced proliferation and reduced apoptosis in C1498 cells. Concurrently, M1-exo-derived PGAM5 decreased mitochondrial membrane potential and increased calcium influx in vitro. In vivo, studies showed that knockdown of PGAM5 in M1-exo elevated liver and spleen weights, augmented tumor size, and intensified hepatic inflammatory infiltration. Our study reveals that M1-exo induces mitochondrial dysfunction against leukemia through PGAM5.

Research Progress on the Anti-Breast Cancer Effect and Mechanism of Oxymatrine

Oxymatrine (OMT), an alkaloid derived from Sophora flavescens, possesses a diverse array of pharmacological activities, encompassing anti-inflammatory, antiviral, antitumor, and immune regulatory properties. In recent times, significant strides have been made in investigating the efficacy of OMT against breast cancer. OMT exerts its anticancer influence through various mechanisms, including inhibition of tumor cell proliferation, suppression of tumor cell invasion and migration, induction of tumor cell apoptosis, and disruption of the cell cycle. This article systematically reviews the underlying mechanisms of OMT in breast cancer therapy by conducting a comprehensive search across multiple databases, such as CNKI, Wanfang, and PubMed, utilizing keywords like "OMT," "breast cancer," "pharmacology," and "pharmacokinetics," as well as incorporating both Chinese and English terms for "OMT," "triple-negative breast cancer," and "breast cancer." The objective is to delve into the potential applications of OMT in breast cancer treatment and furnish a valuable reference for future clinical investigations exploring the utilization of OMT in this field.

Single-cell transcriptome profiling of m6A regulator-mediated methylation modification patterns in elderly acute myeloid leukemia patients

Millions of people worldwide die of acute myeloid leukaemia (AML) each year. Although N6-methyladenosine (m6A) modification has been reported to regulate the pathogenicity of AML, the mechanisms by which m6A induces dysfunctional hematopoietic differentiation in elderly AML patients remain elusive. This study elucidates the mechanisms of the m6A landscape and the specific roles of m6A regulators in hematopoietic cells of elderly AML patients. Notably, fat mass and obesity-associated protein (FTO) was found to be upregulated in hematopoietic stem cells (HSCs), myeloid cells, and T-cells, where it inhibits their differentiation via the WNT signaling pathway. Additionally, elevated YT521-B homology domain family proteins 2 (YTHDF2) expression in erythrocytes was observed to negatively regulate differentiation through oxidative phosphorylation, resulting in leukocyte activation. Moreover, IGF2BP2 was significantly upregulated in myeloid cells, contributing to an aberrant chromosomal region and disrupted oxidative phosphorylation. m6A regulators were shown to induce abnormal cell-cell communication within hematopoietic cells, mediating ligand-receptor interactions across various cell types through the HMGB1-mediated pathway, thereby promoting AML progression. External validation was conducted using an independent single-cell RNA sequencing (scRNA-Seq) dataset. The THP-1 and MV411 cell lines were utilized to corroborate the m6A regulator profile; in vitro experiments involving short hairpin RNA (shRNA) targeting FTO demonstrated inhibition of cell proliferation, migration, and oxidative phosphorylation, alongside induction of cell cycle arrest and apoptosis. In summary, these findings suggest that the upregulation of m6A regulators in HSCs, erythrocytes, myeloid cells, and T-cells may contribute to the malignant differentiation observed in AML patients. This research provides novel insights into the pathogenesis of AML in elderly patients and identifies potential therapeutic targets.

Butyrate as a Potential Modulator in Gynecological Disease Progression.

This review investigates the therapeutic potential of butyrate, a short-chain fatty acid (SCFA) produced by gut microbiota, in the prevention and treatment of various gynecological diseases, including polycystic ovary syndrome (PCOS), endometriosis, and gynecologic cancers like cervical and ovarian cancer. These conditions often pose treatment challenges, with conventional therapies offering limited and temporary relief, significant side effects, and a risk of recurrence. Emerging evidence highlights butyrate's unique biological activities, particularly its role as a histone deacetylase (HDAC) inhibitor, which allows it to modulate gene expression, immune responses, and inflammation. In PCOS, butyrate aids in restoring hormonal balance, enhancing insulin sensitivity, and reducing chronic inflammation. For endometriosis, butyrate appears to suppress immune dysregulation and minimize lesion proliferation. Additionally, in cervical and ovarian cancers, butyrate demonstrates anticancer effects through mechanisms such as cell cycle arrest, apoptosis induction, and suppression of tumor progression. Dietary interventions, particularly high-fiber and Mediterranean diets, that increase butyrate production are proposed as complementary approaches, supporting natural microbiota modulation to enhance therapeutic outcomes. However, butyrate's short half-life limits its clinical application, spurring interest in butyrate analogs and probiotics to maintain stable levels and extend its benefits. This review consolidates current findings on butyrate's multifaceted impact across gynecological health, highlighting the potential for microbiota-centered therapies in advancing treatment strategies and improving women's reproductive health.

Metal Doping Enabling Defective CoMo-Layered Double Hydroxide Nanosheets as Highly Efficient Photosensitizers for NIR-II Photodynamic Cancer Therapy.

Photodynamic therapy (PDT) is attracting widespread attention as a promising strategy for tumor treatment. However, the efficacy of PDT is severely limited by the insufficient tissue penetration depth of the light source and low reactive oxygen species (ROS) generation efficiency. Herein, the metal doping strategy is reported to construct a series of defect-rich M-doped amorphous CoMo-layered double hydroxide (a-M-CoMo-LDH, M = Mn, Cu, Al, Ni, Mg, Zn) photosensitizers (PSs) for NIR-II PDT. Especially, M-doped CoMo-LDH nanosheets are synthesized through a simple hydrothermal method and then etched by acid treatment to prepare defect-rich a-M-CoMo-LDH nanosheets. Under NIR-II 1270 nm laser irradiation, the defect-rich a-Zn-CoMo-LDH nanosheets exhibit the optimal PDT performance compared with other a-M-CoMo-LDH nanosheets, and also possess much higher ROS production activity (3.9 times) than that of the pristine a-CoMo-LDH, with a singlet oxygen quantum yield up to 1.86, which is the highest among all the reported PSs. After polyethylene glycol (PEG) modification, the a-Zn-CoMo-LDH-PEG nanosheets can function as an effective inorganic PS for PDT, effectively inducing cell apoptosis in vitro and eradicating tumors in vivo. Notably, transcriptome sequencing analysis and further molecular validation highlight the critical role of the apoptotic/p53/AMPK/oxidative phosphorylation signaling pathways in a-Zn-CoMo-LDH-PEG-induced cancer cell apoptosis.

Antiproliferative Activity of Antioxidants-Rich Extracts from Olea europaea L. Leaves and Oil Against Six Cancerous Human Cell Lines

ABSTRACT The present work aims to study the cytotoxic effect of the methanolic extract of leaves and oil of three olive cultivars: Manzanillo, Picual and Koronieki. Against six cancer cell lines, namely MCF-7 and MDA (breast cancer), HepG2 (liver cancer), PC3 (prostate cancer), Caco-2 (colon cancer), and A549 (lung cancer) using the MTT method. The results obtained showed that Manzanillo leaf methanolic extract (LMME) and Manzanillo oil (OMME) gave the highest cytotoxicity with the lowest IC50 against Caco2 and A549 cell lines. To explain this result, the mechanism of action was studied at the chemical, cellular and molecular levels. The chemical composition analysis of LMME and OMME was performed by GC-MAS. Furthermore, phytochemical analysis was performed. In addition to cell cycle analysis and apoptosis induction, the gene expression of three apoptotic genes was measured. The total phenolic contents (TPC) and total flavonoid contents (TFC) of (LMME) were greater than that of (OMME). Both LMME and OMME had arrested cell cycle at G1 phase for each of Caco2 and A549 cells. LMME and OMME induce up regulation of Casp3 and BAX genes and down regulation of Bcl-2 gene. These results indicated that, LMME and OMME had anti-proliferation effect against Caco2 and A549 cells through induction of apoptosis pathway. Further detailed studies are needed to examine the effect of each fraction of whole extract.

Nimotuzumab and irinotecan synergistically induce ROS-mediated apoptosis by endoplasmic reticulum stress and mitochondrial-mediated pathway in cervical cancer.

Irinotecan (CPT-11), a chemotherapeutic agent used to treat several types of cancer, induces cytotoxic effects on healthy cells. The epidermal growth factor receptor (EGFR) plays a crucial role in various forms of cancer. Nimotuzumab (NmAb), a monoclonal antibody that targets the EGFR, is utilized in some countries to treat malignancies that have an overexpression of EGFR. Yet, there is a lack of literature on the potential anticancer properties of the CPT-11 and NmAb combination on in vitro human cervical cancer cells. This study investigates the apoptosis mode of the CPT-11 and NmAb combination on cervical HeLa cancer cells. The Annexin V/propidium iodide staining examination demonstrated that the combination of CPT-11 and NmAb resulted in a decrease in the number of viable cells and more potent induction of cell apoptosis than the effects of CPT-11 or NmAb alone in HeLa cells. Furthermore, the combined treatment resulted in elevated levels of reactive oxygen species (ROS) and Ca2+ compared to the treatment with CPT-11 or NmAb alone. Cells that were pretreated with N-acetyl-l-cysteine, a substance that scavenges ROS, and then treated with CPT-11, NmAb, or a combination of CPT-11 and NmAb exhibited higher numbers of viable cells compared to those treated with CPT-11 or NmAb alone. The combination of CPT-11 and NmAb resulted in significantly higher caspase-3, -8, and -9 activity levels than CPT-11 or NmAb alone, as measured by flow cytometer assay. The combination of CPT-11 and NmAb in HeLa cells resulted in elevated endoplasmic reticulum stress-, mitochondria-, and caspase-mediated proteins compared to treatment with CPT-11 or NmAb alone. According to these observations, NmAb enhances the effectiveness of CPT-11 in fighting cancer by stimulating cell death in the HeLa cells. Therefore, NmAb has the potential to improve the efficacy of CPT-11 as a future cervical cancer treatment in humans.

Newcastle disease virus infection induces parthanatos in tumor cells via calcium waves.

Parthanatos is distinct from caspase-dependent apoptosis in that it does not necessitate the activation of caspase cascades; Instead, it relies on the translocation of Apoptosis-inducing Factor (AIF) from the mitochondria to the nucleus, resulting in nuclear DNA fragmentation. Newcastle Disease Virus (NDV) is an oncolytic virus that selectively targets and kills tumor cells by inducing cell apoptosis. It has been reported that NDV triggers classic apoptosis through the mitochondrial pathway. In this study, we observed that NDV infection induced endoplasmic reticulum stress (ERS), which caused a rapid release of endogenous calcium ions (Ca2+). This cascade of events resulted in mitochondrial depolarization, loss of mitochondrial membrane potential, and structural remodeling of the mitochondria. The overload of Ca2+ also initiated an increase in mitochondrial membrane permeability, facilitating the transfer of AIF to the nucleus to induce apoptosis. Damaged mitochondria produced excessive reactive oxygen species (ROS), which further exacerbated mitochondrial damage and increased mitochondrial membrane permeability, thus promoting additional intracellular Ca2+ accumulation and ultimately triggering an ROS burst. Collectively, these findings indicate that NDV infection promotes excessive calcium accumulation and ROS generation, leading to mitochondrial damage that releases more calcium and ROS, creating a feedback loop that exacerbates AIF-dependent parthanatos. This study not only provides a novel perspective on the oncolytic mechanism of NDV but also highlights new targets for antiviral research.

The Effects of Phenylpropanoid and Aurone Compounds on Cell Cycle Modulation and Apoptosis Induction in 4T1 Breast Cancer Cells

The Effects of Phenylpropanoid and Aurone Compounds on Cell Cycle Modulation and Apoptosis Induction in 4T1 Breast Cancer Cells

TRIM16 and PRC1 Are Involved in Pancreatic Cancer Progression and Targeted by Delphinidin.

Pancreatic cancer (PC) is the leading cause of cancer-related death worldwide, and new biomarkers, therapeutic targets, and candidate drugs are needed. In this work, three PC-related microarray datasets (GSE183795, GSE28735, and GSE62452) were analyzed. The differentially expressed genes (DEGs) of PC were obtained with the limma package in R. Weighted gene co-expression network analysis (WGCNA) and machine learning approaches were used to screen the hub genes. Kaplan-Meier plotter and receiver operating characteristic (ROC) curve analysis were utilized to assess the diagnostic efficacy of the hub genes. The binding ability between natural bioactive ingredients and hub proteins was evaluated by molecular docking and molecular dynamics simulation. CCK-8, flow cytometry, transwell, and western blot assays were used to analyze the viability, apoptosis, cell cycle progression, invasion, and pathway change of PC cells. Additionally, a nude mice model was used to evaluate the aggressive properties of PC cells invivo. In this study, a total of 988 DEGs were identified, which were mainly enriched in cell adhesion and PI3K-Akt signaling pathway, and two core genes TRIM16 and PRC1 were further identified. The overall survival of patients with high expression of TRIM16 and PRC1 was shorter. Delphinidin (Del) had good binding affinity with both TRIM16 and PRC1, and Del could inhibit the viability, invasion, and metastasis of PC cells and induce cell apoptosis and G0/G1 phase arrest. In addition, Del could promote the activation of p53 and inhibit the activation of the PI3K/AKT signaling pathway in PC cells. In summary, TRIM16 and PRC1 are identified as prognostic biomarkers and therapeutic targets for PC, and Del has good binding affinity with them and may be a potential therapeutic agent for PC.

Protopanaxadiol triggers G0/G1 cell cycle arrest and apoptosis in human cervical cancer HeLa cells through the PPER pathway

Protopanaxadiol (PPD) is considered to be the most active pharmacological element in ginseng and has been widely studied for its anticancer effects. However, the detailed anticancer mechanism of this compound in cervical cancer (CC) HeLa cells has yet to be thoroughly understood. In this research, we discovered that PPD effectively inhibits CC HeLa cell proliferation and cause morphological changes, with an IC50 measured at 34.18 μM. Based on mRNA-seq analysis, we revealed the mechanism by which PPD inhibits HeLa cell proliferation. The results from Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated significant enrichment of DGEs in the cell cycle and protein processing in the endoplasmic reticulum (PPER) pathway. By inducing DNA damage, PPD resulted in G0/G1 phase cell cycle arrest, inhibited Bcl-2 to cause ROS production, upregulated cytochrome c (Cyto-c) expression, thereby further reducing mitochondrial membrane potential (Δψm), activated the caspase family, and induced cell apoptosis. In addition, PPD promoted Ca2+ leakage, downregulated the PPER pathway (PERK, ATF6, and IRE1α), increased Chop expression levels, and mediated programmed cell death. These observations imply that PPD can induce apoptosis in HeLa cells, highlighting its potential as a novel natural therapeutic for cervical cancer.

Research Progress on the Anticancer Activity of Plant Polysaccharides.

Tumor is a serious threat to human health, with extremely high morbidity and mortality rates. However, tumor treatment is challenging, and the development of antitumor drugs has always been a significant research focus. Plant polysaccharides are known to possess various biological activities. They have many pharmacological properties such as immunomodulation, antitumor, antiviral, antioxidative, antithrombotic, and antiradiation effects, reduction of blood pressure and blood sugar levels, and protection from liver injury. Among these effects, the antitumor effect of plant polysaccharides has been widely studied. Plant polysaccharides can inhibit tumor proliferation and growth by inhibiting tumor cell invasion and metastasis, inducing cell apoptosis, affecting the cell cycle, and regulating the tumor microenvironment. They also have the characteristics of safety, high efficiency, and low toxicity, which can alleviate, to a certain extent, the adverse reactions caused by traditional tumor treatment methods such as surgery, radiotherapy, and chemotherapy. Therefore, this paper systematically summarizes the direct antitumor effects of plant polysaccharides, their regulatory effects on the tumor microenvironment, and intervening many common high-incidence tumors in other ways. It also provides data support for the administration of plant polysaccharides in modern tumor drug therapy, enabling the identification of new targets and development of new drugs for tumor therapy.