Apoptosis In Carcinoma Cells Research Articles

SPINK13 acts as a tumor suppressor in hepatocellular carcinoma by inhibiting Akt phosphorylation.

The PI3K/Akt pathway is overexpressed in nearly 50% of hepatocellular carcinomas and inhibits apoptosis by promoting the expression of antiapoptotic genes. Serine protease inhibitors have been shown to induce apoptosis in hepatoma cells by downregulating SPINK13 in the PI3K/Akt pathway. In this study, SPINK13 was expressed in lentiviral vectors. Changes in signaling pathway adapter proteins, apoptosis regulatory proteins, cell cycle regulatory proteins, and the biological behavior of hepatocellular carcinoma were observed in cell and nude mouse xenograft models. The underlying mechanism of endogenous SPINK13-induced apoptosis in hepatocellular carcinoma cells was explored via transcriptomics. As a result, endogenous SPINK13 might inhibit the activity of Furin protease, downregulate the Notch1/Hes1 pathway in a binding manner, activate the direct effector PTEN, inhibit Akt phosphorylation, inactivate the downstream PI3K/Akt pathway, and ultimately lead to mitochondrial apoptosis and cell cycle arrest in hepatoma cells. Therefore, the Notch1/Hes1/PTEN pathway may act upstream of SPINK13 to downregulate the PI3K/Akt signaling pathway. Our study helps elucidate the underlying mechanism of SPINK13 in anti-hepatocellular carcinoma and lays a theoretical foundation for the development of novel therapeutic serine protease inhibitors.

Asparaginase and isoaspartyl peptidase 1 RNA interference suppresses the growth of nasopharyngeal carcinoma cells

Nasopharyngeal carcinoma (NPC) is one of the common malignant tumors, and its pathogenesis has not been fully clarified. This study aims to explore the impact of RNA interference on the growth and invasion of NPC cells. Asparaginase and isoaspartyl peptidase 1 (ASRGL1)-short hairpin(sh) RNA expressing lentivirus was used to investigate the effect of ASRGL1 knockdown on NPC cells (C666-1 and SUN-1). The target shASRGL1 gene was determined by mRNA and protein expression in nasopharyngeal carcinoma cells; nasopharyngeal carcinoma cell proliferation viability, migration, invasion, apoptosis, ATP levels, and oxidative stress were examined. The results found that ASRGL1 was found to be highly expressed in NPC tissues and cell lines. shASRGL1 exhibited a high gene expression knockdown efficiency, downregulated the ASRGL1 protein expression in the nasopharyngeal carcinoma cells, suppressed proliferation viability of transfected nasopharyngeal carcinoma cells, inhibited their migration and invasion and ATP levels, promoted nasopharyngeal carcinoma cell apoptosis, ROS, and ferroptosis. shASRGL1 plays a role in protecting against NPC cell growth and invasion.

Raddeanin A Suppresses Intracellular 5Methylcytosine (5mC) DNA Modification Engaged the Metastasis of Hepatocellular Carcinoma (HCC)

Ethnopharmacological relevanceThe Anemonoides Raddeana (Rege) Holubhe is commonly employed in clinical practice as a traditional Chinese medicine for the treatment of conditions such as rheumatism and limb numbness. Raddeanin A (RA), an active compound derived from this Traditional Chinese Medicine (TCM), demonstrates specific anticancer properties against many tumorigeneses. However, the molecular mechanism underlying its effects on hepatocellular carcinoma (HCC) remains unexplored. Aim of the studyThe aim of this study is to investigate the inhibitory effects of RA in human HCC stimulated cells and its impact on DNA methylation in tumor cells, as well as to elucidate the molecular mechanisms underlying RA's anti-tumor activity. Materials and MethodsThe inhibitory effects of RA on QGY-7703 and HepG2 cells were evaluated. The IC50 values were determined by employing non-linear sigmoidal curve fitting to analyze the normalized response. The impact of RA was investigated in cells overexpressing DNMT3A and DNMT3B. The effects of RA on cell cycle progression and apoptosis were assessed. Furthermore, the influence of RA on cellular methylation was determined, along with its effects on the expression levels of DNMT3A, DNMT3B, Bcl-2, Bax, and Caspase-3. ResultsThe findings demonstrate that RA induces cell cycle arrest at the G0/G1 phase and promotes apoptosis in hepatocellular carcinoma cells. Furthermore, RA effectively inhibits the invasion and migration of human HCC stimulated cells. The expression of DNMT3A and DNMT3B is downregulated by RA, effectively suppressing the intracellular 5mC DNA modification level. Moreover, the overexpression of these enzymes in RA-treated human HCC stimulated cells significantly impacts the overall 5mC level and hinders tumor metastasis by restricting migration and invasion. ConclusionThe RA compound acts as an antagonist against HCC by reducing intracellular DNA 5mC levels through mechanisms mediated by methyltransferase. Moreover, RA demonstrates the capacity to induce apoptosis in tumor cells, thereby exerting its anti-tumor effects. The findings of this study provide valuable insights for enhancing the pharmacodynamic efficacy of RA in HCC treatment.

2,2'- Bipyridine Derivatives Exert Anticancer Effects by Inducing Apoptosis in Hepatocellular Carcinoma (HepG2) Cells.

To elucidate the therapeutic potential of 2,2'-bipyridine derivatives [NPS (1-6)] on hepatocellular carcinoma HepG2 cells. The effects on cell survival, colony formation, cellular and nuclear morphology, generation of reactive oxygen species (ROS), change in the integrity of mitochondrial membrane potential (MMP), and apoptosis were investigated. Additionally, docking studies were conducted to analyze and elucidate the interactions between the derivatives and AKT and BRAF proteins. NPS derivatives (1, 2, 5 and 6) significantly impaired cell viability of HepG2 cell lines at nanogram range concentrations - 72.11 ng/mL, 154.42 ng/mL, 71.78 ng/mL, and 71.43 ng/mL, while other derivatives were also effective at concentrations below 1µg/mL. These compounds reduced the colony formation capacity of HepG2 cells in a dose-dependent manner following treatment. Mechanistic studies revealed that these derivatives induce reactive oxygen species (ROS) accumulation and cause mitochondrial membrane depolarization, ultimately triggering apoptosis in HepG2 cells. In the presence of these derivatives, cells demonstrated that 75% of cells underwent apoptosis, compared to 25% in the control group. Additionally, there was a marked increase in mitochondrial depolarization (95% cells) and a threefold rise in ROS levels compared to the controls. Docking studies revealed interactions between the derivatives and the signaling proteins AKT (PDB ID: 6HHF) and BRAF (PDB ID: 8C7Y) with binding affinities ranging from -7.10 to -9.91, highlighting their pivotal role in targeting key players in hepatocellular carcinoma progression. The findings of this study underscore the therapeutic potential of these derivatives against HepG2 cells and offer valuable insights for further experimental validation of their efficacy as inhibitors targeting AKT or BRAF signaling pathways.

Diagnostic and Prognostic Potential of FBXO8 Expression in Kidney Renal Clear Cell Carcinoma and Its Regulation of Renal Adenocarcinoma Cells

BackgroundThe F-box protein 8 Gene (FBXO8) has been shown to suppress invasion and metastasis in various cancer types. Recurrence and drug resistance pose significant challenges in renal cell carcinoma (RCC). Identifying novel biomarkers is crucial for addressing these issues. MethodsData on RNA sequencing and patient survival for KIRC was obtained from The Cancer Genome Atlas (TCGA), UALCAN, and Gene Expression Omnibus (GEO) databases. We confirmed FBXO8 gene expression and its impact on survival. Clinical characteristics were classified, and FBXO8 expression differences among various categories were observed. We conducted biofunctional predictions and analyzed the tumor microenvironment (TME), immune cell infiltration, and immune checkpoints in relation to FBXO8 expression. FBXO8 was overexpressed using a plasmid, and we assessed Kidney renal clear cell carcinoma (KIRC) cell proliferation, migration, and apoptosis through CCK8, wound healing tests, and western blot analysis. ResultsOur findings revealed decreased FBXO8 expression in KIRC, with patients exhibiting low FBXO8 expression experiencing shorter survival times. The low expression group showed elevated TME immune and estimate scores. Biofunctional analyses indicated that FBXO8 expression was notably linked to drug metabolism cytochrome P450, nutrition disease, receptor-ligand activity, and neuroactive ligand-receptor interaction. Furthermore, we discovered significant correlations between FBXO8 expression and immune cell infiltration, as well as checkpoints such as CD274. Overexpression (OE) of FBXO8 led to a marked reduction in cell proliferation and migration, along with increased apoptosis, as evidenced by apoptosis-related protein expression. ConclusionThis study demonstrates that FBXO8 serves as a biomarker for KIRC and plays a role in regulating cell proliferation, migration, and apoptosis.

Nerolidol inhibits proliferation and triggers ROS-facilitated apoptosis in lung carcinoma cells via the suppression of MAPK/STAT3/NF-κB and P13K/AKT pathways.

Lung cancer (LC) is the leading cause of malignancy-related mortalities globally, and the existing treatment interventions are associated with harmful side effects. In the current study, we evaluated the anti-tumor efficiency of nerolidol (NRD) on human non-small cell lung cancer (NSCLC) cells. Nerolidol is a sesquiterpene alcohol extracted from the essential oils of aromatic flora with known anti-cancer activities. The latent action of NRD on antiproliferative and apoptotic effects in A549 cells is uncertain. Thus, our work is designed to explore the antiproliferative and apoptotic actions of NRD (20 and 25 μM/mL) against A549 cells. The activity of NRD on A549 cell cytotoxicity, intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), apoptosis, anti-apoptotic proteins, and MAPK/TAT3/NF-κB and P13K/AKT signaling pathways were assessed using MTT tests, dichlorodihydrofluorescein diacetate (DCFH-DA), dual acridine orange/ethidium bromide (AO/EB), DAPI, Rh-123, reverse transciption polymerase chain reaction (RT-PCR), and western blot analyses. We found that NRD could inhibit NSCLC cell viability through elevated intracellular ROS and MMP loss and elicited apoptosis in a quantity-dependent manner. Similarly, NRD can reduce inflammatory cytokines and anti-apoptotic elements, as well as trigger apoptotic signaling pathways. Our data established that NRD decreases A549 cell proliferation through ROS-mediated apoptosis, triggering the MAPK/STAT3/NF-κB and P13K/AKT pathways, suggesting that NRD is a possible protective remedy for NSCLC.

Y27632 induces tongue squamous cell carcinoma cell apoptosis through MAPK-ERK/JNK signal

Abstract Objectives ROCK signaling is considered a therapeutic target for oral squamous cell carcinoma (OSCC). Y27632, a well-established ROCK inhibitor, has previously been reported to block oral squamous cell carcinoma cell growth and has shown cell type dependence in the treatment of other cancers. TP53 is one of the most frequently mutated genes in head and neck cancer. Here, we aim to investigate the role of Y27632 in wild-type and p53 mutant (R175H) SCC9 cells. Methods The p53-mutation (R175H) and p53-null SCC9 cell line were conducted, then, CCK8, colony formation, wound-healing assays, and transwell assay were employed to investigate the role of Y27632 in wtp53 and mutp53 SCC9 cells. The effects of Y27632 in SCC9 cells were also confirmed by the knockdown of ROCK1/2. Additionally, cell cycle and apoptosis were assessed using flow and western blot analysis. The impact of Y27632 on cell senescence was confirmed through the senescence-associated β-gal staining. Furthermore, the inhibition of Y27632 was examined in vivo using tumor-bearing nude mice. Results Our study demonstrates that Y27632 effectively impeded the proliferation of tongue squamous cell carcinoma (TSCC) cells in vitro and in vivo. Additionally, the proliferation and migration of wtp53 and mutp53 SCC9 cells were also significantly suppressed by Y27632 or ROCK siRNA in vitro. Mechanistically, Y27632 induced apoptosis in SCC9 cells via the MAPK-ERK/JNK signaling pathway. Conclusions Our data demonstrated that Y27632 induces apoptosis in SCC9 cells via the MAPK-ERK/JNK signaling pathway, regardless of the presence of p53 mutant variants (R175H). This will provide a potential therapeutic drug for TSCC treatment in the future.

Retracted: Boschniakia rossica Polysaccharide Triggers Laryngeal Carcinoma Cell Apoptosis by Regulating Expression of Bcl-2, Caspase-3, and P53.

The Editors of Medical Science Monitor wish to inform you that the above manuscript has been retracted from publication due to concerns with the credibility and originality of the study, the manuscript content, and the Figure images. Reference: Chunping Yao, Xiujuan Cao, Zheng Fu, Jing Tian, Wei Dong, Jin Xu, Kang An, Limin Zhai, Jinming Yu. Boschniakia rossica Polysaccharide Triggers Laryngeal Carcinoma Cell Apoptosis by Regulating Expression of Bcl-2, Caspase-3, and P53. Med Sci Monit, 2017; 23: 2059-2064. DOI: 10.12659/MSM.901381.

Hyaluronic acid-zein shell-core biopolymer nanoparticles enhance hepatocellular carcinoma therapy of celastrol via CD44-mediated cellular uptake

Low concentrations or limited residence times in tumor tissues, making celastrol (Cel) difficult to exert significant therapeutic effects. Thus, we developed Zein/hyaluronic acid core-shell nanoparticles (Cel/Zein@HA NPs) for active targeted delivery of Cel via CD44 receptor over-expression on cancer cells, which may strengthen the therapeutic efficacy of Cel and improve delivery targeting. Cel-loaded Zein nanoparticles (core), are elegantly enveloped by a hydrophilic HA coating that forms the shell, resulting in significantly improved encapsulation efficiency and ensured good stability. The cellular uptake of Cel/Zein@HA NPs in HepG2 cells was 1.57-fold higher than nontargeting Cel/Zein NPs. Near-infrared fluorescence imaging confirmed the accumulation of Cel/Zein@HA NPs in H22 liver cancer tumors in mice, resulting in effective antitumor effects and good biosafety. Besides, in vitro and in vivo experiments showed that compared with Cel/Zein NPs, Cel/Zein@HA NPs had more efficient inhibitory effect on tumor proliferation and lower systemic toxicity. Further studies revealed that Cel/Zein@HA NPs induced apoptosis in hepatocellular carcinoma cells by modulating Bax and Bcl-2 expression, while also inhibiting tumor angiogenesis by decreasing CD31 and VEGF levels. Overall, this study presents a promising strategy for enhancing targeted liver cancer therapy through the utilization of biopolymer nanoparticle-based nano-pharmaceuticals that facilitate CD44-mediated cellular uptake.

Evodiamine inhibits proliferation and induces apoptosis of nasopharyngeal carcinoma cells via the SRC/ERBB2-mediated MAPK/ERK signaling pathway

This study aimed to investigate the effect and potential mechanism of evodiamine (EVO) on proliferation and apoptosis of nasopharyngeal carcinoma (NPC) cells. EVO inhibited proliferation, blocked cell cycle progression, and induced apoptosis of NPC cells. There are 27 known anti-NPC targets of EVO, of which eight are core targets, namely SRC, ERBB2, STAT3, MAPK8, NOS3, CXCL8, APP, and HDAC1. Molecular docking analysis showed that the binding of EVO with its key targets (SRC, ERBB2) was good. EVO also reduced the expression of SRC and ERBB2, the key proteins p-MEK and p-ERK1/2 of the MAPK/ERK signaling pathway, and the downstream proteins PCNA and XIAP. EVO inhibited the growth of NPC xenografts in nude mice and reduced the expression levels of SRC, ERBB2, ERK1/2, p-ERK1/2, PCNA and XIAP in NPC tissue. When the MAPK/ERK signaling pathway was activated by epidermal growth factor (EGF), the expression levels of PCNA and XIAP increased, the cell proliferation index increased, and the apoptosis rate decreased in the EGF + EVO treatment group compared to treatment with EVO alone. These changes indicated that the inhibitory effect of EVO on proliferation and apoptosis of NPC cells was related to the down-regulation of SRC and ERBB2 expression, and further inhibition of the MAPK/ERK signaling pathway.

Gintonin-Enriched Panax ginseng Extract Fraction Sensitizes Renal Carcinoma Cells to TRAIL-Induced Apoptosis through DR4/5 Upregulation.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising chemotherapeutic agent because of its selective apoptotic action on cancer cells. However, resistance to TRAIL-induced apoptosis remains a challenge in many cancers. The gintonin-enriched Panax ginseng extract fraction (GEF) has diverse pharmacological benefits. We explored the combined efficacy of GEF and TRAIL in inducing apoptosis in human renal cell carcinoma (RCC) cells. The effect of GEF treatment on the viability, clonogenic potential, wound healing, and TRAIL-induced apoptotic signaling of RCC cells was studied in vitro. Our investigation revealed that GEF pre-treatment sensitized RCC cells to TRAIL-induced apoptosis, as evidenced by DNA fragmentation and cell proliferation, colony formation, and migration inhibition. This sensitization was linked to the upregulation of death receptors 4 and 5 and alterations in apoptotic protein expression, notably, the decreased expression of the Mu-2-related death-inducing gene, a novel anti-apoptotic protein. Our findings underscore the necessity of caspase activation for GEF/TRAIL-induced apoptosis using the pan-caspase inhibitor Z-VAD-FMK. This study demonstrates that GEF sensitizes human RCC cells to TRAIL-induced apoptosis by upregulating DR4/5 and modulating apoptotic protein expression. These findings suggest a promising strategy for overcoming TRAIL resistance in cancer therapy and highlight the potential of GEF as a valuable adjunct to TRAIL-based treatments.

Morusin, a novel inhibitor of ACLY, induces mitochondrial apoptosis in hepatocellular carcinoma cells through ROS-mediated mitophagy

ObjectiveMorusin (Mor), a prenylated flavonoid isolated from the root bark of Morus alba L., exhibits potent anti-tumour effects; however, the molecular target of Mor is still not entirely clear. This study aimed to elucidate the mechanism of Mor against hepatocellular carcinoma (HCC) and identify potential molecular targets. MethodsMitochondrial function was assessed by measuring the mitochondrial membrane potential, mitochondrial ultrastructure, oxygen consumption, and ATP levels. Mor-induced mitophagy was confirmed using western blotting, immunofluorescence, and fluorescent probes. Transcriptomics, flow cytometry, western blotting, qRT-PCR and biochemical assays were used to reveal the molecular mechanisms and targets of Mor against HCC. We further validated the interaction between Mor and the target proteins using molecular docking and biolayer interferometry (BLI). The inhibitory effect of Mor in vivo was evaluated using a Hep3B murine xenograft model. ResultsMor significantly reduced the ATP citrate lyase (ACLY) expression and inhibited ACLY activity in HCC cells. BLI analysis demonstrated a direct interaction between Mor and the ACLY active domain. Mor-induced ACLY inhibition led to ROS accumulation in HCC cells, which caused mitochondrial damage, triggered PINK1/Parkin-mediated mitophagy, and ultimately induced mitochondrial apoptosis. We further verified that ROS is crucial in the apoptotic action of Mor through experiments regarding an ROS scavenger. Mor also significantly inhibited tumour xenograft growth in vivo. In addition, analysis of human liver cancer clinical samples revealed elevated ACLY levels positively correlated with histologic grade. ConclusionCollectively, our findings highlight Mor as a potent bioactive inhibitor of ACLY and a promising candidate for HCC therapy.

Isoliquiritigenin Modulates the Effect of LINC01503 on Lung Squamous Carcinoma Cells

Isoliquiritigenin (ISL) is an important pharmacological constituent of Glycyrrhiza glabra, which possesses a range of physiological and pharmacological activities, as well as significant antitumor activity, and can be used as a potential drug for targeted cancer therapy. LINC01503 is an oncogene, which has been closely associated with the malignant biological processes of many cancers. The aim of this study was to investigate the effects of ISL on the proliferation, apoptosis, invasion and migration of lung squamous carcinoma cells by regulating LINC01503. Plasma was collected from lung squamous carcinoma patients and healthy individuals treated at Tangshan People's Hospital from January 2021 to December 2022. The expression of LINC01503 in lung squamous carcinoma plasma, tissues and cells was detected by real-time quantitative fluorescence polymerase chain reaction (qRT-PCR). Lung squamous carcinoma cells were treated with different concentrations of ISL for 24 h, and LINC01503 expression was detected by qRT-PCR. The cells were treated in groups: si-NC group, si-LINC01503 group, DMSO (0.1% dimethyl sulfone) group, ISL group, pc DNA3.1(+)-NC group, pc DNA3.1(+)-LINC01503 group, ISL+pc DNA3.1(+)-NC group and ISL+pc DNA3.1(+)- LINC01503 groups. CCK-8 assay, clone formation assay, flow cytometry, Transwell assay and scratch assay were used to explore the effect of LINC01503 on the functional phenotype of lung squamous carcinoma cells. Fluorescence in situ hybridization results showed that the average fluorescence intensity of LINC01503 in tissue microarrays of lung squamous carcinoma patients was higher than that in paracancerous tissues (P<0.05). The expression of LINC01503 in the plasma of patients with lung squamous carcinoma was higher than that in the plasma of healthy individuals (P<0.05). Knockdown of LINC01503 inhibited the proliferation, invasion and migration of lung squamous carcinoma cells and promoted apoptosis (P<0.05). ISL inhibited the proliferation, invasion, migration and promoted apoptosis of lung squamous carcinoma cells (P<0.05). Overexpression of LINC01503 followed by intervention with ISL reversed the promotional effect of overexpression of LINC01503 on the proliferation, invasion and migration of lung squamous carcinoma cells as well as the inhibitory effect on apoptosis (P<0.05). LINC01503 was highly expressed in lung squamous carcinoma, and LINC01503 could promote the proliferation, invasion and migration of lung squamous carcinoma cells and inhibit the apoptosis, ISL could inhibit the proliferation, invasion and migration of lung squamous carcinoma cells and promote apoptosis of lung squamous carcinoma cells by regulating the expression of LINC01503.

Activating Transcription Factor 5; A Potential Prognostic Molecular Biomarker for Cervical Cancer (CC)

Background: Prognostic biomarkers with high sensitivity and specificity that accurately predict disease prognosis are crucial for influencing cancer patients' treatment and disease progression choices. This research attempts to determine ATF5's cervical cancer prognostic value and find a theoretical basis for cervical cancer treatment. Method: This study began with a survival analysis, then univariate and multivariate analyses using transcriptomics, methylation, and TCGA ATF5 clinical data. Second, ATF5's role in cervical cancer development was explored using GO, KEGG, and TIMER databases. We assessed ATF5's cervical cancer treatment potential using CMap, a drug development tool. Results: After conducting several analyses, we discovered that high levels of ATF5 mRNA expression and low levels of methylation were beneficial for patients with cervical cancer prognosis. An important finding is that ATF5 may promote apoptosis in cervical carcinoma cells. In addition, we assessed the therapeutic potential of four small molecules against cervical cancer. ATF 5 function as a tumor suppressor gene in cervical cancer has been demonstrated for the first time using numerous databases and bioinformatics techniques from multiple dimensions, which is a novel aspect of this research. Moreover, the finding that ATF5 is a biomarker that can contribute to the apoptosis of cervical cancer cells and predict a favorable prognosis for the disease was an additional innovation. In the future, ATF5 can be used as a therapeutic target and to develop anti-cancer medications.

Selective cytotoxicity of standardised n-hexane extract of black soldier flies’ larvae on cancerous skin cells mitochondria isolated from rat model of melanoma

Introduction Melanoma is known as a highly lethal cancer. In melanoma cells, apoptosis signalling which relies heavily on the acute activity of mitochondria and reactive oxygen species (ROS) formation is suppressed. Our previous studies on natural compounds on melanoma suggested that mitochondria are a potential target for the melanoma treatment by selective cytotoxic effect of them. The black soldier fly is an important environmental protectant insect that based on recent studies induces apoptosis in liver and colorectal carcinoma cells through the activation of caspase 3, 8, and 9 and ultimately inhibits the growth of cancer cells. Purpose This study was designed to evaluate the selective apoptotic effect of the n-hexane BSFL extract (BSFLE) on skin mitochondria. Materials and Methods The mitochondria isolated from melanoma cells were treated with various concentrations (1500, 3000, and 6000 µg/ml) of n-hexane BSFLE Then MTT viability assay, ROS determination, Mitochondrial Membrane Potential (MMP), mitochondrial swelling, cytochrome c release determination, and % apoptosis were performed. Results MTT assay showed that different concentrations of n-hexane BSFLE significantly (P < 0.05) decreased the SDH activity in cancerous skin mitochondria with the IC50. The ROS production and mitochondrial swelling results also showed that all concentrations of BSFL extracts significantly increased. MMP decline and the release of cytochrome c in cancer groups mitochondria. BSFLE increased apoptosis on melanoma cells. Discussion and Conclusion It is suggested that n-hexane BSFLE compounds selectively induce a cascade of proapoptotic events that are probably defective in cancer cells. Most of these compounds target the mitochondrial transient pore caused by disruption of the mitochondrial respiratory chain. These events lead to disruption of the temporary permeability of mitochondria, swelling of mitochondria and finally the formation of apoptosome in the cytosol.

Aqueous Extracts of Ocimum gratissimum Sensitize Hepatocellular Carcinoma Cells to Cisplatin through BRCA1 Inhibition.

Ocimum gratissimum (O. gratissimum), a medicinal herb with antifungal and antiviral activities, has been found to prevent liver injury and liver fibrosis and induce apoptosis in hepatocellular carcinoma (HCC) cells. In this study, we evaluated the effect of aqueous extracts of O. gratissimum (OGE) on improving the efficacy of chemotherapeutic drugs in HCC cells. Proteomic identification and functional assays were used to uncover the critical molecules responsible for OGE-induced sensitization mechanisms. The antitumor activity of OGE in combination with a chemotherapeutic drug was evaluated in a mouse orthotopic tumor model, and serum biochemical tests were further utilized to validate liver function. OGE sensitized HCC cells to the chemotherapeutic drug cisplatin. Proteomic analysis and Western blotting validation revealed the sensitization effect of OGE, likely achieved through the inhibition of breast cancer type 1 susceptibility protein (BRCA1). Mechanically, OGE treatment resulted in BRCA1 protein instability and increased proteasomal degradation, thereby synergistically increasing cisplatin-induced DNA damage. Moreover, OGE effectively inhibited cell migration and invasion, modulated epithelial-to-mesenchymal transition (EMT), and impaired stemness properties in HCC cells. The combinatorial use of OGE enhanced the efficacy of cisplatin and potentially restored liver function in a mouse orthotopic tumor model. Our findings may provide an alternate approach to improving chemotherapy efficacy in HCC.

Knockdown of sulfotransferase 2B1 suppresses cell migration, invasion and promotes apoptosis in ovarian carcinoma cells via targeting annexin A9.

Sulfotransferase family 2B member 1 (SULT2B1) has been reported to play oncogenic role in many types of cancers. Nevertheless, the role that SULT2B1 played in ovarian cancer (OC) and the hidden molecular mechanism is obscure. Expression of SULT2B1 in OC was analyzed by GEPIA database. qRT-PCR and western blot (WB) was applied for the appraisement of SULT2B1 and Annexin A9 (ANXA9) in OC cell lines. The capabilities of cells to proliferate, migrate and invade were assessed with CCK-8 assay, wound healing assay, along with transwell assay. Cell apoptotic level was estimated utilizing flow cytometry. WB was employed for the evaluation of migration- and apoptosis-related proteins. Bioinformatic analysis and co-immunoprecipitation were used to predict and verify the combination of SULT2B1 and ANXA9. The data showed that SULT2B1 and ANXA9 were upregulated in OC cells. SULT2B1 depletion suppressed the proliferative, migrative, and invasive capabilities of SKOV3 cells but facilitated the cell apoptosis. SULT2B1-regulated ANXA9 expression and were proved to bind to ANXA9. Additionally, ANXA9 deficiency exhibited the same impacts on cell migrative, invasive capability and apoptotic level as SULT2B1 silencing. Moreover, ANXA9 overexpression reversed the inhibitory impacts of SULT2B1 silencing on the proliferative, migrative, invasive, and apoptotic capabilities of SKOV3 cells. In summary, SULT2B1 silencing repressed OC progression by targeting ANXA9.

The expression and biological role of complement C1s in esophageal squamous cell carcinoma.

The present work focused on investigating the role of the altered expression of complement C1s in proliferation and apoptosis of esophageal squamous cell carcinoma (ESCC) cells and explore its biological functions in ESCC, so as to lay a theoretical foundation and provide certain clinical reference for diagnosing and treating ESCC. Complement C1s expression within ESCC was assessed, and its clinical pathological characteristics in ESCC patients were analyzed. Subsequently, in vitro experiments were performed to further explore the mechanisms by which complement C1s affected ESCC. According to the results, complement C1s expression within ESCC markedly increased relative to adjacent non-cancerous samples. High C1s expression showed positive relation to race, residual lesion, and tumor location of ESCC patients. Complement C1s affected ESCC cell proliferation and apoptosis. Notably, C1s knockdown significantly inhibited ESCC cell proliferation and enhanced their apoptosis. C1s suppressed ESCC cell proliferation via Wnt1/β-catenin pathway and promoted their apoptosis through modulating the expression of Bcl2, Bax, and cleaved-caspase3.

The effect of different parameters of low-level laser used in the treatment of oral mucositis, on the viability and apoptosis of oral squamous cell carcinoma cells: Invitro study.

Oral mucositis is a complication of chemo/radiotherapy. To assess the impact of various power levels of diode-laser on the survival and expression of apoptosis-related genes in oral cancer cells, it is crucial to consider the potential existence of malignant cells within the treatment region and the reliance of laser effectiveness on its specific characteristics. Cal-27 cells were cultivated and exposed to a 660 nm-diode-laser at power levels of 20, 40, and 80 mW, alongside non-irradiated control cells. Viability and expression of Bax and Bcl-2 mRNA were assessed with Methyl Thiazolyl Tetrazolium (MTT) and Real-time Polymerase Chain Reaction (RT-PCR), respectively. The results were analyzed using one-way ANOVA and Tukey post-hoc test (p < 0.05). A significant reduction in viability was found only in the 20 mW group compared to controls (p = 0.001). Cell survival was significantly lower in cells receiving 20 mW laser than those treated with 40 and 80 mW (p < 0.05). None of the laser groups showed significant changes in BcL-2, but Bax was significantly lower in cells receiving 40 and 80 mW (p < 0.05), compared to controls. Laser irradiation at 660 nm (2 J/cm2, 30 s) significantly reduced the viability of oral cancer cells when using 20 mW power. These specifications align with the recommendation that the lowest possible laser dose should be applied for treating cancer patients. The exact mechanism of cell death following laser therapy with these specifications requires further investigation.

Extracellular Membrane Vesicles of Escherichia coli Induce Apoptosis of CT26 Colon Carcinoma Cells.

Escherichia coli (E. coli) is commonly utilized as a vehicle for anti-tumor therapy due to its unique tumor-targeting capabilities and ease of engineering modification. To further explore the role of E. coli in tumor treatment, we consider that E. coli outer membrane vesicles (E. coli-OMVs) play a crucial role in the therapeutic process. Firstly, E. coli-OMVs were isolated and partially purified by filtration and ultracentrifugation, and were characterized using techniques such as nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) and Western Blot (WB). The obtained extracellular nanoparticles, containing OMVs, were found to inhibited the growth of CT26 tumor in mice, while the expression of Bax protein was increased and the expression of Bcl-2 protein decreased. In vitro experiments showed that E. coli-OMVs entered CT26 cells and inhibited cell proliferation, invasion and migration. In addition, in the presence of E. coli-OMVs, we observed an increase in apoptosis rate and a decrease in the ratio of Bcl-2/Bax. These data indicate that E. coli-OMVs inhibits the growth of CT26 colon cancer by inducing apoptosis of CT26 cells. These findings propose E. coli-OMVs as a promising therapeutic drug for colorectal cancer (CRC), providing robust support for further research in related fields.