Apoptosis In A549 Cells Research Articles

Synergistic Anti-Cancer Activities of Curcumin Derivative CU17 Combined with Gemcitabine Against A549 Non-Small-Cell Lung Cancer Cells

Recently, the curcumin derivative CU17 possessing HDAC inhibitory activity has been shown to synergistically enhance the anti-proliferative activity of Gem against lung cancer cells. Nevertheless, the mechanism(s) underlying the synergistic anti-cancer effect remains to be investigated. This study aimed to investigate the mechanisms that underpin the anti-cancer activity of the combined Gem and CU17 against NSCLC A549 cells both in vitro and in mouse xenograft models. CU17 was successfully synthesized and subsequently investigated for its combination effects with Gem on inductions of cell cycle arrest and apoptosis in A549 cells. The combination treatment substantially decreased cell survival through S phase prolongation and G2/M phase cell cycle arrest via up-regulating the expressions of p21 and p53 proteins. Additionally, CU17 potentiated the apoptotic effect of Gem in A549 cells by increasing the Bax/Bcl-2 ratio. The co-treatment resulted in an up-regulation of pERK1/2 and Ac-H3 expression. An in vivo study demonstrated that CU17 significantly improved the anti-cancer effect of Gem in nude mice utilizing A549 cell xenografts. The hematoxylin and eosin (H&E) staining results indicated that CU17 decreased the toxicity of Gem to the liver, kidneys, and spleen. Overall, CU17 enhanced the effectiveness of Gem while decreasing its toxicity. This compound shows promise as a chemosensitizer for NSCLC treatment with Gem.

Synthesis, cytotoxicity, apoptosis-inducing activity and molecular docking studies of novel isatin-podophyllotoxin hybrids.

Podophyllotoxin, along with its numerous derivatives and related compounds, is well known for its broad-spectrum pharmacological activity, especially for anticancer potential. In this study, several isatin-podophyllotoxin hybrid compounds were successfully synthesized with good yields through microwave-prompted three-component reactions of 2-amino-1,4-naphthoquinone, various substituted isatins, and tetronic acid. Their cytotoxicity was assessed against four types of human cancer cell lines, HepG2 (hepatoma carcinoma), MCF7 (breast cancer), A549 (non-small lung cancer), and KB (epidermoid carcinoma), alongside nontumorigenic HEK-293 human embryonic kidney cells. Among 14 compounds screened, 7f possessed the strongest cytotoxicity to KB and A549 cell lines, with IC50 values of 1.99 ± 0.22 and 0.90 ± 0.09 μM, respectively. Further studies revealed that product 7f could arrest the cell cycle of A549 cells at S phase and induce apoptosis of A549 cells. This compound was examined for its binding ability against cyclin-dependent kinases (CDKs) and procaspase/caspase systems. The results indicated that 7f exhibited significant interactions with the residues of the ATP binding sites of CDK2/cyclin A and CDK5/p25 and also activated procaspase 6 through stable zinc chelation. Additionally, physicochemical and pharmacokinetic properties related to drug-likeness, in parallel with toxicity, were computationally assessed to identify the main issues that need to be addressed in structural optimization. Taken together, compound 7f was identified as a potent cytotoxic agent that could be considered for anticancer drug discovery and development.

Cobalt oxide nanoparticles induce cytotoxicity and excessive ROS mediated mitochondrial dysfunction and p53-independent apoptosis in melanoma cells

Nanotherapy has emerged as a promising strategy for the targeted and efficient treatment of melanoma, the most aggressive and lethal form of skin cancer, with minimized systemic toxicity. However, the therapeutic efficacy of cobalt oxide nanoparticles (Co3O4NPs) in melanoma treatment remains unexplored. This study aimed to assess the therapeutic potential of Co3O4NPs in melanoma treatment by evaluating their impact on cell viability, genomic DNA and mitochondrial integrity, reactive oxygen species (ROS) generation and apoptosis induction in melanoma A-375 cells. Our findings demonstrated a concentration-dependent reduction in cell viability upon treatment with five Co3O4NP concentrations (0.2, 2, 20, 200, and 2000 µg/ml), with an IC50 value of 303.80 µg/ml. Treatment with this IC50 concentration significantly increased ROS generation, induced dramatic DNA damage, and disrupted mitochondrial membrane potential integrity. Flow cytometric analysis revealed apoptosis and necrosis induction following Co3O4NP exposure at the IC50 concentration value. Results of qRT-PCR analysis demonstrated remarkable dysregulation of apoptotic and mitochondrial genes, including a significant downregulation of apoptotic p53 and mitochondrial ND3 genes and marked upregulation of the anti-apoptotic gene Bcl2. These findings highlight the novel potential of Co3O4NPs as potent inducers of melanoma A-375 cell death in a concentration-dependent manner through excessive ROS production, genomic instability, mitochondrial dysfunction and dysregulation of apoptotic and mitochondrial gene expression, ultimately promoting apoptosis in A-375 cells. This study thus underscores the potential of Co3O4NPs as a promising nanotherapeutic candidate for melanoma treatment, warranting further exploration to elucidate their full biological and clinical applicability.

Therapeutic Scrutiny of Lentinus polychrous with Attention to Its Antioxidant, Antimicrobial, and Anticancer Attributes.

Mushrooms, being a source of therapeutically active compounds, are of great interest to researchers due to their historical usage in traditional therapies and the significant role that natural products have played in the development of contemporary medications. Lentinus polychrous is one underutilized mushroom species collected from the laterites of West Bengal, India. Our study aims toward its taxonomic validation, deciphering the secondary metabolic fingerprint, and testing its efficiency in countering many clinical issues, including oxidative stress, growing microbial drug resistance, and cancer. In vitro investigations have shown that the methanolic extract of the mushroom has a broad spectrum of antioxidant activitieswith effective concentration (EC50) ranging from 403.6 ± 3.8 to 841.2 ± 10.7µg/mL depending on the type of free radicals and is effective in combating human pathogenic bacterial strains where MIC50 varies from as low as 302.2 ± 3.8 to 570.6 ± 1.8µg/mL, mediated likely through inducing the breakdown of the outer coat and inducing increased porosity. The fraction was also shown to possess anticancer properties against A549 cells (LD50 120.9 ± 1.83µg/mL) by triggering apoptosis. The modulation of Bcl-2 family gene expression was found to be the primary factor responsible for the induction of apoptosis in A549 cells during the experimental approaches. The findings revealed that the mushroom exhibits significant antioxidant, antibacterial, and particular cytotoxic effects on lung cancer cells, indicating its potential medical importance. These results provide essential insights into possibilities for the development of new therapeutic medicines derived from this mushroom.

Microwave-assisted synthesis and in vitro and in silico studies of pyrano[3,2-c]quinoline-3-carboxylates as dual acting anti-cancer and anti-microbial agents and potential topoisomerase II and DNA-gyrase inhibitors.

A microwave-assisted method was utilized to synthesize novel pyranoquinolone derivatives as dual acting topoisomerase II/DNA gyrase inhibitors with apoptosis induction ability for halting lung cancer and staphylococcal infection. Herein, the designed rationale was directed toward mimicking the structural features of both topoisomerase II and DNA gyrase inhibitors as well as endowing them with apoptosis induction potential. The absolute configuration of the series was assigned using X-ray diffraction analysis. Cytotoxic activity against NSCLC A549 cells showed that ethyl 2-amino-9-bromo-4-(furan-2-yl)-5-oxo-5,6-dihydro-4H-pyrano[3,2-c]quinoline-3-carboxylate (IC50 ≈ 35 μM) was the most potent derivative in comparison to the positive control Levofloxacin and was selected for further investigation to assess its selectivity (SI = 1.23). Furthermore, in vitro antibacterial screening revealed the potential activity of this bromo derivative against Staphylococcus aureus. Mechanistic studies showed that the aforementioned compound exhibited promising inhibitory activity against topoisomerase II (IC50 = 45.19 μM) and DNA gyrase (IC50 = 40.76 μM) compared to reference standards. In addition, the previous compound induced a A549 cell apoptosis by 38.49-fold and it also increased the total apoptosis by 20.4% compared to a 0.53% increase in the control. Docking simulations postulated its interactions and suggested well fitting into its molecular targets.

PLAC8 attenuates pulmonary fibrosis and inhibits apoptosis of alveolar epithelial cells via facilitating autophagy

Idiopathic pulmonary fibrosis (IPF) is an irreversible lung condition that progresses over time, which ultimately results in respiratory failure and mortality. In this study, we found that PLAC8 was downregulated in the lungs of IPF patients based on GEO data, in bleomycin (BLM)-induced lungs of mice, and in primary murine alveolar epithelial type II (pmATII) cells and human lung epithelial cell A549 cells. Overexpression of PLAC8 facilitated autophagy and inhibited apoptosis of pmATII cells and A549 cells in vitro. Moreover, inhibition of autophagy or overexpression of p53 partially abolished the effects of PLAC8 on cell apoptosis. ATII cell-specific overexpression of PLAC8 alleviated BLM-induced pulmonary fibrosis in mice. Mechanistically, PLAC8 interacts with VCP-UFD1-NPLOC4 complex to promote p53 degradation and facilitate autophagy, resulting in inhibiting apoptosis of alveolar epithelial cells and attenuating pulmonary fibrosis. In summary, these findings indicate that PLAC8 may be a key target for therapeutic interventions in pulmonary fibrosis.

Identification of narciclasine as a novel NRF2 inhibitor

Cancer genome sequencing studies have identified somatic mutations in the KEAP1/NRF2 pathway. In an effort to identify novel NRF2 small molecule inhibitor(s), we have screened a natural compound library comprising 1,330 chemicals in A549-ARE-GFP-luciferase cells and identified that narciclasine significantly inhibits NRF2-dependent luciferase activity. Narciclasine suppressed the expression of NRF2 and NRF2 target genes, caused significant oxidative stress, and sensitized cisplatin-mediated apoptosis in A549 cells. In addition, we have observed that WD Repeat Domain 43 (WDR43) serves as a direct target of narciclasine for the inhibition of NRF2 as narciclasine binds to recombinant WDR43 in vitro and silencing WDR43 attenuated the inhibition of NRF2 by narciclasine in A549 cells. Finally, we observed that administration of narciclasine significantly decreased the growth of A549 xenografts. Together, our results demonstrate that the inhibition of NRF2 by narciclasine is mediated by WDR43 and future studies are necessary to elucidate the exact mechanism how WDR43 mediates the inhibition of NRF2 by narciclasine.

Apocynin Induces Apoptosis in Human Lung Cancer A549 Cells via Regulating Apoptotic Protein and Inflammatory Cytokines

Apocynin Induces Apoptosis in Human Lung Cancer A549 Cells via Regulating Apoptotic Protein and Inflammatory Cytokines

Design, synthesis, and biological evaluation of evodiamine-indolequinone hybrids as novel NQO1 agonists against non-small cell lung cancer

NQO1 is a FAD containing NAD(P)H-dependent oxidoreductase that catalyzes the reduction of quinones and related substrates, which plays an important role in the treatment of non-small cell lung cancer (NSCLC). Based on the indolequinone structure from 5-methoxy-2-methylindole, the indolequinone of NQO1 agonists was first coupled with amino-evodiamine derivatives by esterification reaction, and sixteen new compounds targeting NQO1 were developed. Among them, compounds 11b and 12d (IC50 = 2.72 or 3.66 µM, respectively) were showed better activity by cytotoxicity assay than the reference drug EVO (IC50 = 19.65 µM). Furthermore, the results of flow cytometry analysis showed that compounds 11b and 12d promoted apoptosis in A549 cells, blocked the cell cycle to the G2/M stage and caused a burst of reactive oxygen species. Western blotting experiments revealed that compounds 11b and 12d, after 24 h of treatment in A549 cells, downregulate the expression of Keap1 while upregulating the expression of Nrf2, NQO1, and HO-1. This suggests that compounds 11b and 12d increase cellular antioxidant capacity by regulating the Keap1/Nrf2/NQO1 antioxidant pathway. In vivo anti-tumor experiments showed that the reference drugs EVO (TGI = 15.94 %) and 5-Fu (TGI = 27.54 %) inhibited the proliferation of tumor tissue, while compound 11b could better inhibit the proliferation of tumor tissue (TGI = 39.13 %). In conclusion, our research results suggest that compounds 11b and 12d are potent agonism of the NQO1 signaling pathway and provide a potential opportunity to improve the treatment of NSCLC.

Two multifunctional zero-dimensional Gd(III) complexes: magnetocaloric effect and anticancer mechanisms for lung cancer.

Two Gd(III) complexes [GdL(H2O)(NO3)2(CH3OH)0.75(CH3CH2OH)0.25] (Gd1) and [Gd2(OOCCH3)2L2(H2O)6]•2(H2O) (Gd2) (HL=2-pyridylcarboxaldehyde isonicotinoylhydrazone) were synthesized with a Schiff base ligand. Crystallographic study reveals both Gd1 and Gd2 have a zero-dimensional mononuclear or binuclear structure. Magnetic investigations demonstrate that Gd1 and Gd2 exhibit potential magnetocaloric effects due to Gd(III) ions, which provide negligible magnetic anisotropy, and possess low-lying excited spin states. The antiproliferative activity of Gd1 and Gd2 to three tumor cell lines was conducted and the results showed Gd1 and Gd2 showed more pronounced antiproliferative activity to A549 cells better than cisplatin. The administration of Gd1 and Gd2 led to an increase in apoptosis among A549 cells in a concentration-dependent manner, along with a corresponding rise in the levels of reactive oxygen species (ROS) within the cells. Besides, Gd1 and Gd2 were able to significantly inhibit tumor cell migration. Cell cycle assay in A549 cells revealed that cell cycle was arrested of G0/G1 phase. Western blotting analysis showed that Gd1 and Gd2 complexes could promote apoptosis in A549 cells by modulating the expression of Bcl-2 and Bax proteins.

Rapid isolation of cytotoxic daphnane diterpenoids from Daphne altaica Pall. using MS-DIAL.

Daphnane diterpenoids occurring in plants of the Thymelaeaceae are the focus of natural product drug discovery because of the wide range of their therapeutically biological activities. Considering the limited occurrence in some plants of the Thymelaeaceae, it is imperative to design a strategy for the target isolation of daphnane diterpenoids. In this study, a strategy was developed to filter the data using MZmine, generate the molecular network using the Global Natural Product Social Molecular Network Platform (GNPS), and determine the retention time of target compounds using MS-DIAL. Under the guidance of the approach which integrates the analysis of LC-MS/MS, compounds 1-5, representative diterpenoids from Daphne altaica Pall., were isolated. Their structures were determined through detailed spectroscopic analyses and ECD calculations. The growth-inhibitory activities of the isolated compounds against MCF-7, A549, and HepG2 cell lines was examined. Notably, compound 1 demonstrated the most noticeable cytotoxicity, exhibiting potent growth inhibition activities against A549 and HepG2 cells with IC50 values of 2.89 μM and 5.30 μM, respectively. Further morphological and staining analyses corroborated that compound 1 induced apoptosis in A549 and HepG2 cells, highlighting its potential as a bioactive agent.

The anticancer mechanisms of Toxoplasma gondii rhoptry protein 16 on lung adenocarcinoma cells

ABSTRACT Lung adenocarcinoma is the most prevalent subtype of lung cancer, which is the leading cause of cancer-related mortality worldwide. Toxoplasma gondii (T.gondii) Rhoptry protein 16 (ROP16) has been shown to quickly enter the nucleus, and through activate host cell signaling pathways by phosphorylation STAT3 and may affect the survival of tumor cells. This study constructed recombinant lentiviral expression vector of T. gondii ROP16 I/II/III and stably transfected them into A549 cells, and the effects of ROP16 on cell proliferation, cell cycle, apoptosis, invasion, and migration of A549 cells were explored by utilizing CCK-8, flow cytometry, qPCR, Western blotting, TUNEL, Transwell assay, and cell scratch assay, and these effects were confirmed in the primary human lung adenocarcinoma cells from postoperative cancer tissues of patients. The type I and III ROP16 activate STAT3 and inhibited A549 cell proliferation, regulated the expression of p21, CDK6, CyclinD1, and induced cell cycle arrest at the G1 phase. ROP16 also regulated the Bax, Bcl-2, p53, cleaved-Caspase3, and Caspase9, inducing cell apoptosis, and reduced the invasion and migration of A549 cells, while type II ROP16 protein had no such effect. Furthermore, in the regulation of ROP16 on primary lung adenocarcinoma cells, type I and III ROP16 showed the same anticancer potential. These findings confirmed the anti-lung adenocarcinoma effect of type I and III ROP16, offering fresh perspectives on the possible application of ROP16 as a target with adjuvant therapy for lung adenocarcinoma and propelling the field of precision therapy research toward parasite treatment of tumors.

15-Deoxy-Δ-12,14-Prostaglandin J2 Represses Immune Escape of Lung Adenocarcinoma by Polarizing Macrophages Through Epidermal Growth Factor Receptor/Ras/Raf Pathway.

Lung adenocarcinoma (LUAD) is a widespread and deadly form of cancer. Prostaglandin 15-deoxy-Δ-12,14-prostaglandin J2 (15d-PGJ2) possesses antioxidant, anti-inflammatory, and anticancer properties. However, it is unclear whether this effect on LUAD progression stems from its ability to influence macrophage polarization. By utilizing 3- (4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, colony formation, transwell assays, and enzyme linked immunosorbent assay (ELISA), we investigated how 15d-PGJ2 affects A549 cell viability, proliferation, apoptosis, and invasion, as well as levels of interleukin (IL)-4, IL-13, and IL-17. Human monocytic cell line THP-1 was induced into M2 macrophages using phorbol 12-myristate 13-acetate and IL-4/IL-13, followed by treatment with 15d-PGJ2. The study employed flow cytometry to observe the polarization of macrophages, quantitative reverse transcription polymerase chain reaction (qRT-PCR) to identify epidermal growth factor receptor (EGFR) expression, western blot for identifying expression of macrophage marker proteins, and examining EGFR/rat sarcoma (Ras)/rapidly accelerated fibrosarcoma (Raf) activation. In a coculture setup, CD8+ T cells were shown to have a proliferation capacity by carboxifluorescein diacetate succinimidyl ester (CFSE), a killing ability by lactate dehydrogenase, and an analysis of their interferon gamma and tumor necrosis factor alpha levels by ELISA. 15d-PGJ2 reduced invasion capacity and expression of inflammatory cytokines, lowered A549 cell viability in a dose-dependent way, and promoted apoptosis. 15d-PGJ2 facilitated the transition of M2 macrophages to the M1 type, inhibited Ras/Raf pathway activation, reduced EGFR expression in macrophages, and stimulated CD8+ T cells to enhance anti-tumor immunity. 15d-PGJ2 repressed M2 macrophage polarization and LUAD immune evasion by targeting the EGFR/Ras/Raf pathway in macrophages.

Dexmedetomidine Regulates Macrophage Phenotype Remodeling Through AMPK/SIRT1 to Alleviate Inflammatory Mediators and Lung Injury.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is associated with high morbidity and mortality in the intensive care unit (ICU) and can cause excessive inflammation. Dexmedetomidine (DEX) is a drug that exerts anti-inflammatory effects. Identifying the anti-inflammatory mechanism of DEX in the context of ALI/ARDS possesses potential significance for the prevention and treatment of ARDS. In this study, DEX was used to treat mouse models of cecal ligation and puncture (CLP) and lipopolysaccharide (LPS)-stimulated cells. Immunofluorescence, western blot analysis, and flow cytometry were used to detect macrophage phenotypic markers in mice, and western blot analysis, real-time qPCR (RT-qPCR), ELISA, and immunofluorescence were used to detect macrophage phenotype markers in RAW264.7 cells. Flow cytometry was used to detect phenotypic markers of bone marrow-derived macrophages (BMDM). Culture medium collected from macrophages was used to cultivate human non-small cell adenocarcinoma epithelial cells (A549) to detect their aquaporins 1 (AQP1) expression and apoptosis status. Western blot analysis was used to detect the activation of the AMP-activated protein kinase (AMPK)/sirtuin 1(SIRT1) signaling pathway both in vivo and in vitro. The regulatory effect of DEX on macrophage phenotype remodeling was detected by knocking down AMPK expression in cells using AMPK shRNA. The results showed that in both in vivo and in vitro experiments, DEX downregulated the expression of M1 markers (tumor necrosis factor-α [TNF-α], nitric oxide synthase [iNOS], and cluster of differentiation [CD]-86) and upregulated the expression of M2 markers (arginase-1 [ARG-1], interleukin [IL]-10, and CD206) in macrophages. The culture medium of macrophages treated with DEX alleviated the edema and apoptosis of A549 cells. DEX activates the AMPK/SIRT1 signaling pathway in macrophages. After AMPK knockdown, the ability of DEX to regulate macrophage phenotype remodeling decreased. Together, this study suggests that DEX regulates macrophage phenotype remodeling by activating the AMPK/SIRT1 pathway, thereby reducing ALI/ARDS.

Potent Anti-Cancer Activity of 1-Dehydrodiosgenone from the Product of Microbial Transformation of Steroid Saponins.

Steroids are extensively used in the pharmaceutical industry as industrial raw materials for the production of anti-inflammatory and anti-tumor drugs. Microbial transformation, an environmentally friendly method, displays the potential for preparing steroids on an industrial scale. In this study, four steroids, including Diosgenin, Smilagenone, Yamogenin, and 1-Dehydrodiosgenone, were isolated and identified from the solid-state fermentation (SSF) product of a novel Fusarium oxysporum strain, and their anti-tumor activities were investigated. The cytotoxicity assay showed that 1-Dehydrodiosgenone had significant inhibitory effects on three tumor cell lines, Hala, A549, and Mad-MB468 cells, with IC50s of 6.59 μM, 5.43 μM, and 4.81 μM, respectively. 1-Dehydrodiosgenone significantly induced apoptosis and necrosis of Hala, A549, and Mad-MB468 cells by upregulating the expressions of cleaved caspase-3, cleaved PARP, Bax, and Bad. Moreover, no significant organ damage was observed in mice based on safety tests. Therefore, 1-Dehydrodiosgenone is expected to be developed as a safe and broad-spectrum anti-cancer agent.

Verbascum ponticum (Stef.) Extract Induces Lung Cancer Apoptosis via Mitochondrial-Dependent Apoptosis Pathway.

Non-small-cell lung carcinoma remains a significant health concern due to its high incidence and mortality rates. Traditional medicines play a central role in cancer therapy, with plant-derived bioactive compounds being studied for their potential to offer fewer side effects than conventional treatments. In traditional Kurdish medicine, different Verbascum species are used to treat burns, inflammation, and other conditions. While some species extracts have shown cytotoxic effects against several cancer cell lines like A549, the efficacy and mechanisms of action of the other species like Verbascum ponticum (V. ponticum) remain to be elucidated. Therefore, this study aimed to explore the effect of V. ponticum (Stef.) extract, collected from the Kurdistan region of the Iraq mountains, on A549 cells. A comprehensive approach was employed, utilizing immunocytochemical and functional analyses to assess apoptotic morphology, DNA fragmentation, alongside assays for cellular and mitochondrial function, proliferation, and viability. Additionally, the study investigated AIF mitochondrial translocation and evaluated mitochondrial membrane potential using the Rhodamine 123 assay. The results showed that the V. ponticum flower extract induced mitochondrial-mediated apoptosis in A549 cells via disruption of mitochondrial membrane potential, release of AIF, and translocation to the nucleus, independently of the caspase-3-activation pathway. These findings emphasize the potential of V. ponticum in lung cancer strategic treatments, meriting further phytochemical studies to identify the bioactive compounds it contains.

Corynoxine suppresses lung adenocarcinoma proliferation and metastasis via inhibiting PI3K/AKT pathway and suppressing Cyclooxygenase-2 expression

BackgroundLung adenocarcinoma (LUAD) is the most common lung cancer subtype, and the prognosis of affected patients is generally poor. The traditional Chinese medicine Uncaria rhychophaylla has been reported to exhibit anti-lung cancer properties. Accordingly, the main bioactive ingredient in Uncaria rhychophaylla, Corynoxine, may hold great value as a treatment for lung cancer.MethodsThe impact of Corynoxine on the viability of LUAD cells was assessed using the Cell Counting Kit-8 (CCK-8) assay. Apoptosis in A549 cells was evaluated via flow cytometry. Migration and invasion capabilities were determined through wound healing and Transwell assays, respectively. The key pathways targeted by Corynoxine in LUAD were identified using a network pharmacology approach. Additionally, Western immunoblotting, quantitative real-time PCR (qRT-PCR), and ELISA assays were conducted to validate the underlying mechanisms. The in vivo anti-tumor efficacy of Corynoxine was assessed in xenograft nude mice.ResultsIn this study, Corynoxine treatment was found to markedly suppress in vitro LUAD cell proliferative, migratory, and invasive activity. It additionally downregulated Vimentin and promoted E-cadherin upregulation consistent with the disruption of epithelial-mesenchymal transition (EMT) induction while also accelerating apoptotic death. Furthermore, network pharmacology analysis revealed that the PI3K/AKT pathway is a potential target of Corynoxine in LUAD. In vitro assays demonstrated that treatment with Corynoxine resulted in the suppression of PI3K/AKT signaling and a consequent drop in cyclooxygenase-2 (COX-2) expression. These findings were further confirmed in vivo in mice harboring A549 tumor xenografts in which Corynoxine was able to interfere with the PI3K/AKT/COX-2 signaling axis.ConclusionThis study elucidated the potential effects of Corynoxine in suppressing proliferation and metastasis in LUAD, along with investigating the underlying mechanisms. These data highlight the promise of Corynoxine as a novel therapeutic tool for the treatment of individuals diagnosed with LUAD.

Low toxicity ginsenoside Rg1-carbon nanodots as a potential therapeutic agent for human non-small cell lung cancer

Here ginsenoside Rg1 was used to synthesise Rg1 carbon nanodots via a one-step hydrothermal method. The surface of the Rg1 carbon nanodots is rich in hydrophilic functional groups with good water solubility and biocompatibility. The Rg1 carbon nanodots exhibited a high inhibitory effect on the proliferation, migration, and proapoptotic ability of non-small cell lung cancer A549 cells. The changes in the levels of ROS, Ca2+, and MMP in A549 cells after the administration of Rg1 carbon nanodots were evaluated and further correlated with relevant proteins in the caspase apoptotic pathway. Proteomic screening revealed that the Rg1 carbon nanodots could regulate A549 cell apoptosis by activating the expression of MAPK pathway-related proteins. In the in vivo experiment, the therapeutic efficacy of the Rg1 carbon nanodots in inhibiting tumour growth was much higher than that of commonly used chemotherapy drugs, with negligible toxicity and side effects. Immunohistochemical staining showed that the expression of caspase- and MAPK pathway-related proteins in mouse tumour tissues was consistent with that at the cellular level. The results suggest that Rg1 carbon nanodots can promote tumour apoptosis and represent a potential therapeutic agent for human non-small-cell lung cancer.

Electrospun nanofibrous scaffolds reinforced with therapeutic lithium/manganese-doped calcium phosphates: Advancing skin cancer therapy through apoptosis induction

In the current study we fabricated potent materials by incorporating therapeutic elements into calcium phosphates (CPs) to combat cancer. This involved synthesizing manganese (Mn)- and lithium (Li)-doped CPs and loading them into electrospun nanofibers (NFs) composed of chitosan (CS) and polyethylene oxide (PEO). The characterized CPs exhibited excellent properties, including a particle size of 47–75 nm, surface charge of –(30−56) mV, and specific surface area of 75–266 m2/g. The electrochemical analysis revealed that Mn and Mn/Li-doped CPs are promising for generating oxygen free radicals and H2O2, crucial for cancer therapy. Biological evaluation showcased the outstanding performance of the developed materials. MTT assay revealed a cytotoxic effect of nano-constructs on melanoma A375 cell line without adverse effects on normal L929 cells over 72 h. Annexin V/PI apoptosis assay indicated substantial apoptosis rates in A375 cells treated with PC-20 % (62.55 ± 4.59 %). The obtained data of qPCR analysis of pro-apoptotic and anti-apoptotic genes (P53, Bax, Bcl-2) in A375 cells treated with different CP nanoparticles (NPs) showed a significant increase in P53 and Bax gene expression, indicating high levels of A375 cell apoptosis. Additionally, the samples containing Mn ion exhibited high reactive oxygen species (ROS) generation. In conclusion, the fabricated NFs scaffolds hold promising potential for cancer therapy.

Fenbendazole and Diisopropylamine Dichloroacetate Exert Synergistic Anti-cancer Effects by Inducing Apoptosis and Arresting the Cell Cycle in A549 Lung Cancer Cells.

Lung cancer is the leading cause of cancer-related mortality worldwide, accounting for approximately 2 million new cases and 1.8 million deaths annually. Standard treatment options include surgery, radiation therapy, chemotherapy, and targeted therapies. Despite advancements over the past 25 years, the prognosis of patients with lung cancer remains poor. This study evaluated the synergistic anticancer effects of fenbendazole (FZ) and diisopropylamine dichloroacetate (DADA) on A549 lung cancer cells. Fenbendazole (methyl N-(6-phenylsulfanyl-1H-benzimidazol-2-yl) carbamate) is a broad-spectrum benzimidazole anthelmintic commonly used in veterinary medicine. Diisopropylamine Dichloroacetate (DADA), an over-the-counter treatment for chronic liver disease, has demonstrated anti-tumor properties as an inhibitor of pyruvate dehydrogenase kinase. The combination of FZ and DADA exhibited a synergistic effect on inhibiting the proliferation of A549 lung cancer cells. After 48 h of treatment, the FZ-DADA combination produced reactive oxygen species (ROS) and promoted apoptosis by down-regulating Bcl2 and up-regulating BAX protein expression. The combination activated caspase-3, caspase-7, and PARP, further driving apoptosis in A549 cells. The FZ-DADA treatment also induced cell cycle arrest, as evidenced by the inhibition of Cyclin A and Cyclin E proteins. The synergistic anticancer effects of the FZ-DADA combination were confirmed at both cellular and protein levels in A549 lung cancer cells. The combination modulates key apoptotic proteins, induces cell cycle arrest, and increases mitochondrial ROS production, suggesting a promising approach for lung cancer treatment that warrants further investigation and development.