Effect Of 1a Research Articles

Pirin Promotes the Progression of Non-Small-Cell Lung Cancer by Increasing ODC1 to Suppress Autophagy.

Non-small-cell lung cancer (NSCLC), a common malignant tumor, requires deeper pathogenesis investigation. Autophagy is an evolutionarily conserved lysosomal degradation process that is frequently blocked during cancer progression. It is an urgent need to determine the novel autophagy-associated regulators in NSCLC. Here, we found that pirin was upregulated in NSCLC, and its expression was positively correlated with poor prognosis. Overexpression of pirin inhibited autophagy and promoted NSCLC proliferation. We then performed data-independent acquisition-based quantitative proteomics to identify the differentially expressed proteins (DEPs) in pirin-overexpression (OE) or pirin-knockdown (KD) cells. Among the pirin-regulated DEPs, ornithine decarboxylase 1 (ODC1) was downregulated in pirin-KD cells while upregulated along with pirin overexpression. ODC1 depletion reversed the pirin-induced autophagy inhibition and pro-proliferation effect in A549 and H460 cells. Immunohistochemistry showed that ODC1 was highly expressed in NSCLC cancer tissues and positively related with pirin. Notably, NSCLC patients with pirinhigh/ODC1high had a higher risk in terms of overall survival. In summary, we identified pirin and ODC1 as a novel cluster of prognostic biomarkers for NSCLC and highlighted the potential oncogenic role of the pirin/ODC1/autophagy axis in this cancer type. Targeting this pathway represents a possible therapeutic approach to treat NSCLC.

Discovery of potential WEE1 inhibitors via hybrid virtual screening.

G2/M cell cycle checkpoint protein WEE1 kinase is a promising target for inhibiting tumor growth. Although various WEE1 inhibitors have entered clinical investigations, their therapeutic efficacy and safety profile remain unsatisfactory. In this study, we employed a comprehensive virtual screening workflow, which included Schrödinger-Glide molecular docking at different precision levels, as well as the utilization of tools such as MM/GBSA and Deepdock to predict the binding affinity between targets and ligands, in order to identify potential WEE1 inhibitors. Out of ten molecules screened, 50% of these molecules exhibited strong inhibitory activity against WEE1. Among them, compounds 4 and 5 showed excellent inhibitory activity with IC50 values of 1.069 and 3.77nM respectively, which was comparable to AZD1775. Further investigations revealed that compound 4 displayed significant anti-proliferative effects in A549, PC9, and HuH-7 cells and could also induce apoptosis and G1 phase arrest in PC9 cells. Additionally, molecular dynamics simulations unveiled the binding details of compound 4 with WEE1, notably the crucial hydrogen bond interactions formed with Cys379. In summary, this comprehensive virtual screening workflow, combined with in vitro testing and computational modeling, holds significant importance in the development of promising WEE1 inhibitors.

White and black anodic TiO2 nanotubes: Comparison of biological effects in A549 and SH-SY5Y cells

In this work, the cytotoxicity of black TiO2 nanotubes in comparison to their white counterparts is exploited for the first time. To provide a comprehensive overview, the toxicity is also assessed in comparison to multi-walled carbon nanotubes (MWCNTs) using two different cell lines. The TiO2 nanotube layers were prepared by anodic oxidation of Ti foils and investigated in the as-prepared white form, and in the black form, achieved by reduction via comproportionation reaction of Ti and TiO2. Additionally, a part of the black TiO2 nanotube layers was coated with a thin TiO2 coating with a nominal thickness of ~0.275 nm by Atomic Layer Deposition (ALD). Pulmonary A549 cells and neural SH-SY5Y cells were exposed to a wide range of TiO2 nanotube concentrations (1–500 μg/mL) for 24 and 48 h. Then, the cytotoxicity was evaluated using cell viability and glutathione assessments. Essentially, no reduction in cell viability was observed after incubating the cells with TiO2 nanotubes up to 100 μg/mL, while MWCNTs decreased the cell viability at a similar concentration significantly. In addition, ALD TiO2 coating on the black TiO2 nanotubes caused disappearance of mild toxic effects of white and black TiO2 nanotubes due to the shading of carbon and fluorine species incorporated within the TiO2 nanotube walls.

An investigation of Plk1 PBD inhibitor KBJK557 as a tumor growth suppressor in non-small cell lung cancer

Lung cancer is the second most commonly reported type of cancer worldwide. Approximately 80–85% of lung cancer occurrences are accounted by non-small cell lung cancer (NSCLC). Polo-like kinase-1 (Plk1) plays multiple roles in cell cycle progression and its overexpression is observed in majority of malignancies, including NSCLC. A combination of frontline drugs and inhibitors targeting the Plk kinase domain (KD) has been used to overcome drug resistance in NSCLC. Plk1 KD inhibitors are highly prone to cross-reactivity with similar kinases, eventually leading to undesirable side effects. Moreover, there have been no reports of Plk1 PBD inhibitors showing antitumorigenic effects on NSCLC cells or animal models so far. To address this issue herein, for the first time, our recently reported Plk1 PBD inhibitor KBJK557 was evaluated for the anticancer potential against NSCLC cells. KBJK557 displayed notable cytotoxic effects in A549, PC9, and H1975 cells. Mechanistic investigations revealed that KBJK557-treated cells underwent G2/M cell cycle arrest, triggering subsequent apoptosis. In vivo antitumorigenic activity in xenograft mice model demonstrates that KBJK557-treated mice showed a considerable decrease in tumor size, proving the significances of Plk1 in lung cancer. Collectively, this study demonstrates that KBJK557 can serve as a promising drug candidate for treating the lung cancer through Plk1 PBD inhibition.

Exploring the Role of Sodium-Glucose Cotransporter as a New Target for Cancer Therapy

To evaluate the effects of SGLT2 inhibitors on the proliferation, tumorigenesis, migration, colony formation, apoptosis, selected gene expression pattern, and combination with known chemotherapeutic drugs in different human cancer cell lines. The antiproliferative and combined effects of SGLT2 inhibitors were evaluated by MTT assay. Cell migration was assessed using wound-healing and colony formation assays. Apoptosis assay was conducted using annexin V-FITC/ propidium iodide staining. SGLT2 gene expression was determined using real-time PCR. Canagliflozin, dapagliflozin, and ipragliflozin significantly inhibited the growth of different cancer cell lines in a dose and time-dependent manner. IC50 values after 48 hours of treatment with canagliflozin, ipragliflozin, and dapagliflozin ranged from 41.97 µM to 69.49 µM, 63.67 µM to 255.80 µM, and 167.7 µM to 435.70 µM in the examined cancer cell lines, respectively. The combined treatment of SGLT2 with doxorubicin and raloxifene separately resulted in a synergistic effect in Caco-2 and A-549 cell lines. On the other hand, the combination of SGLT2 inhibitors with cisplatin resulted in an antagonistic effect in A-549, Du-145, and Panc-1 cell lines. Canagliflozin and ipragliflozin inhibited cell migration and colony formation ability at IC50 and Sub-IC50 in the examined cancer cell lines. Canagliflozin and ipragliflozin significantly induced apoptosis at IC50 and Double-IC50 in the Du-145 cell line compared to the control. Real-time PCR showed that the treatment with 0.1 IC50 and 0.2 IC50 of both canagliflozin and ipragliflozin resulted in diminished RNA expression of SGLT2, VEGF, and Bcl-2 genes in the Du-145 cell line. SGLT2 inhibitors have antiproliferation, anti-tumorigenesis, and anti-migration effects and may induce apoptosis in cancer cells. In addition, treatment with SGLT2 inhibitors resulted in the downregulation of selected genes in the Du-145 cell line.

Synthesis and Anticancer Potential of New Hydroxamic Acid Derivatives as Chemotherapeutic Agents

Histone deacetylase (HDAC) inhibitors have been shown to induce differentiation, cell cycle arrest, and apoptosis due to their low toxicity, inhibiting migration, invasion, and angiogenesis in many cancer cells. Studies show that hydroxamic acids are generally used as anticancers. For this reason, it is aimed to synthesize new derivatives of hydroxamic acids, to examine the anticancer properties of these candidate inhibitors, and to investigate the inhibition effects on some enzymes that cause multidrug resistance in cancer cells. For this reason, new (4-amino-2-methoxy benzohydroxamic acid (a), 4-amino-3-methyl benzohydroxamic acid (b), 3-amino-5-methyl benzohydroxamic acid (c)) amino benzohydroxamic acid derivatives were synthesized in this study. The effects on healthy fibroblast, lung (A549), and cervical (HeLa) cancer cells were investigated. In addition, their effects on TRXR1, GST, and GR activities, which are important for the development of chemotherapeutic strategies, were also examined. It was determined that molecule b was the most effective molecule in HeLa cancer cells with the lowest IC50 value of 0.54. It was determined that molecule c was the most effective molecules for A549 and HeLa cancer cells, with the lowest IC50 values of 0.78mM and 0.25mM, respectively. It was determined that b and c molecules directed cancer cells to necrosis rather than apoptosis. c molecule showed anticancer effect in A549 and HeLa cancer cells. It was found that molecule c significantly suppressed both GR and TRXR1 activities. In GST activities, however, inhibitors did not have a significant effect on cancer cells.

Multi-stimuli-responsive fluorescence of bibranched bromo-substituted cyanostilbene derivative with aggregation induced emission enhancement and green light-emitting diode

A novel organic multi-stimuli-responsive fluorescence material (2a) was designed, synthesized and characterized. The photophysical properties, solvent effect, acid/base stimulus response and aggregation induced emission (AIE) effect of 2a were tested, and the application of 2a in light-emitting diode (LED) was explored. The results indicate that 2a has aggregation induced emission (AIE) effect owing to its stable conjugated structural unit of cyanostilbene; 2a can be used to estimate the polarity of the solvent using naked eyes or instrument due to its remarkable solvatochromic feature; 2a can be utilized as acid/base indicator due to its sensitive fluorescence respond for acid/base stimulation; In addition, 2a can also be applied in LED based on its desirable solid luminescence.

Scutellarin improves the radiosensitivity of non-small cell lung cancer cells to iodine-125 seeds via downregulating the AKT/mTOR pathway.

BackgroundIn our previous study, we indicated that scutellarin (SCU) induced an anticancer effect in A549 cells. However, whether SCU regulates the radiosensitivity of non‐small cell lung cancer (NSCLC) and its related mechanism is still unclear.MethodsIn this study, we explored the anticancer effect induced by iodine‐125 (125I) and SCU at a sensitizing concentration in A549 and H1975 cells. Cellular apoptosis and proliferation were detected by flow cytometry, Bcl‐2/Bax expression level, cell cycle, CCK‐8, and EdU staining. A tumor model using nude mice was also carried out to investigate the combined effect of 125I and SCU in vivo. In addition, the expression level of AKT/mTOR pathway was detected to investigate whether it is linked to the anticancer effect of 125I and SCU.ResultsSCU at a sensitizing concentration promoted the 125I‐induced apoptosis and antiproliferative effect in A549 and H1975 cells. Moreover, the same results were obtained in vivo. Based on our findings, the AKT/mTOR pathway was significantly downregulated after combined treatment with 125I and SCU.ConclusionsThe results of our study suggested that SCU promotes the anticancer effects induced by 125I in NSCLC cells by downregulating the AKT/mTOR pathway and lays a foundation for future application of this combined treatment.

Highly Aromatic Flavan-3-ol Derivatives from Palaeotropical Artocarpus lacucha Buch.-Ham Possess Radical Scavenging and Antiproliferative Properties.

Phytochemical investigation of leaves and stembark of Artocarpus lacucha collected in Thailand resulted in three yet undescribed isomeric flavan-3-ol derivatives (1–3), the four known compounds gambircatechol (4), (+)-catechin (5), (+)-afzelechin (6) and the stilbene oxyresveratrol (7). Compounds 1 to 3 feature 6/6/5/6/5/6 core structures. All structures were deduced by NMR and MS, while density functional theory (DFT) calculations on B3LYP theory level were performed of compounds 1 to 3 to support the stereochemistry in positions 2 and 3 in the C-ring. Possible biosynthetic pathways leading to 4 are discussed. The DPPH assay revealed high radical scavenging activities for 1 (EC50 = 9.4 ± 1.0 µmol mL−1), 2 (12.2 ± 1.1), 3 (10.0 ± 1.5) and 4 (19.0 ± 2.6), remarkably lower than ascorbic acid (EC50 = 34.9) and α-tocopherol (EC50 = 48.6). A cytotoxicity assay revealed moderate but consistent antiproliferative properties of 1 in CH1/PA-1 (ovarian teratocarcinoma) and SW480 (colon carcinoma) cells, with IC50 values of 25 ± 6 and 34 ± 4 µM, respectively, whereas effects in A549 (non-small cell lung cancer) cells were rather negligible. The performed DCFH-DA assay of 1 in the former cell lines confirmed potent antioxidative effects even in the cellular environment.

RASSF1A Enhances Chemosensitivity of NSCLC Cells Through Activating Autophagy by Regulating MAP1S to Inactivate Keap1-Nrf2 Pathway

ObjectiveCisplatin (DDP) is an effective first-line therapy for non-small cell lung cancer (NSCLC) treatment; however, it can cause resistance and thus pose an obstacle to the efficacy of chemotherapy in NSCLC. This study aims to detect the effect of RASSF1A on DDP resistance of NSCLC and the underlying mechanism.MethodsThe expression levels of RASSF1A and microtubule-associated protein 1S (MAP1S) were investigated by qRT-PCR and Western blot and their interaction was testified by co-immunoprecipitation (Co-IP) analysis. The IC50 value of DDP on A549 and A549/DDP cells (DDP-resistant cells) was measured. A549/DDP cells were transfected with pCDNA3.1-RASSF1A, pCDNA3.1-MAP1S, or si-RASSF1A, followed by treated with DDP. Cell counting kit-8 (CCK-8) and 5-ethynyl-2ʹ-deoxyuridine (EDU) were employed to measure cell survival rate. Western blot was applied to test the levels of autophagy-associated proteins p62, LC3II, and LC3I. Immunofluorescence staining was used to detect the green fluorescent protein (GFP)-LC3 puncta to evaluate the level of autophagy. Finally, a xenograft model in nude mice using A549/DDP cells was developed.ResultsRASSF1A and MAP1S were lowly expressed and positively correlated in NSCLC tissues. We observed that RASSF1A and MAP1S overexpression significantly enhanced DDP-induced effects in A549 and A549/DDP cells, including decreased cell viability, as well as increased autophagy levels. Besides, investigations into the mechanism between RASSF1A and MAP1S disclosed that RASSF1A could regulate MAP1S to inactivate the Keap1-Nrf2 pathway, thus activating autophagy to enhance chemosensitivity. Moreover, consistent results were confirmed in vivo experiments.ConclusionRASSF1A increases chemosensitivity in NSCLC by facilitating autophagy via MAP1S-mediated Keap1-Nrf2 pathway.

Proteasome Inhibitors Diminish c-Met Expression and Induce Cell Death in Non-Small Cell Lung Cancer Cells.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and accounts for 85% of all lung carcinomas. The hepatocyte growth factor receptor (c-Met) has been considered as a potential therapeutic target for NSCLC. Proteasome inhibition induces cell apoptosis and has been used as a novel therapeutic approach for treating diseases including NSCLC; however, the effects of different proteasome inhibitors on NSCLC have not been fully investigated. The aim of this study is to determine a precise strategy for treating NSCLC by targeting c-Met using different proteasome inhibitors. Three proteasome inhibitors, bortezomib, MG132, and ONX 0914, were used in this study. Bortezomib (50 nM) significantly reduced c-Met levels and cell viability in H1299 and H441 cells, while similar effects were observed in H460 and A549 cells when a higher concentration (∼100 nM) was used. Bortezomib decreased c-Met gene expression in H1299 and H441 cells, but it had no effect in A549 and H460 cells. MG-132 at a low concentration (0.5 μM) diminished c-Met levels in H441 cells, while neither a low nor a high concentration (∼20 μM) altered c-Met levels in A549 and H460 cells. A higher concentration of MG-132 (5 μM) was required for decreasing c-Met levels in H1299 cells. Furthermore, MG-132 induced cell death in all four cell types. Among all the four cell lines, H441 cells expressed higher levels of c-Met and appeared to be the most susceptible to MG-132. MG-132 decreased c-Met mRNA levels in both H1299 and H441 cells. ONX 0914 reduced c-Met levels in H460, H1299, and H441 cells but not in A549 cells. c-Met levels were decreased the most in H441 cells treated with ONX 0914. ONX 0914 did not alter cell viability in H441; however, it did induce cell death among H460, A549, and H1299 cells. This study reveals that different proteasome inhibitors produce varied inhibitory effects in NSCLS cell lines.

Combination treatment of Src inhibitor Saracatinib with GMI, a Ganoderma microsporum immunomodulatory protein, induce synthetic lethality via autophagy and apoptosis in lung cancer cells.

Saracatinib is an oral Src-kinase inhibitor and has been studied in preclinical models and clinical trials of cancer therapy. GMI, a fungal immunomodulatory protein from Ganoderma microsporum, possesses antitumor capacity. The aim of this study is to evaluate the cytotoxic effect of combination treatment with saracatinib and GMI on parental and pemetrexed-resistant lung cancer cells. Cotreatment with saracatinib and GMI induced synergistic and additive cytotoxic effect in A549 and A400 cells by annexin V/propidium iodide assay and combination index. Using western blot assay, saracatinib, and GMI combined treatment synergistically induced caspase-7 activation in A549 cells. Different from A549 cells, saracatinib and GMI cotreatment markedly increased LC3B-II in A400 cells. ATG5 silencing abolished the caspase-7 activation and reduced cell death in A549 cells after cotreatment. This is the first study to provide a novel strategy of treating lung cancer with or without drug resistance via combination treatment with GMI and saracatinib.

Potential lung cancer therapy using plant derived cholesterol structural analogs

The acquired multidrug resistance syndrome (MDRS) is one of the leading causes for the failure of chemotherapy in lung cancer. Recently plant‐derived triterpenoids (eg, cholesterol‐structural analogs) have showed a wide spectrum of pharmacological activities. In addition, in different studies, anticancer agents have been combined to cholesterol moieties to improve their cellular uptake and target specificity. Herein, we investigated the cytotoxic activity of various triterpenoids cholesterol analogs: oleanolic acid (OleA), ursolic acid (UrA), betulinic acid (BeA), asiatic acid (AsA), lupeol (Lupe), stigmasterol (Stg) and β‐sitosterol (β‐Sito) on non‐small lung adenocarcinoma cells (A549) and normal lung cells (MRC5). From our studies, the IC 50 for most of these cholesterol‐analogs were in the low μM range after 24h of incubation. β‐Sito and Stg did not show any significant cytotoxic pattern in this μM range. In addition BeA and OleA showed the highest therapeutic indexes comparing the cytotoxic effect in A549 vs MRC5 cells. Metabolic activity assays were performed to determine the mechanism of action of these natural compounds. Caspases activity and cell membrane integrity assays were performed and all the cytotoxic triterpenoids induced no activation of caspase‐3, and high membrane permeabilization. Gene expression assays of MDRS‐related genes (EGF, VEGF, Pgp, Bcl‐2, P 53 , NDRG1, GLIPR1) demonstrated the downregulation of some of these genes after the incubation with these triterpenoids. These results demonstrated that even slight structural changes in these cholesterol analogs can influence the cytotoxic response and cellular mechanistic pathways. Complete results will be presented. This study opens promising perspectives for further research on the role of phytochemical triterpenoids, which ultimately will contribute to a more rational application in cancer therapy.Support or Funding InformationSJB‐Research Center Seed

6-O-(3″, 4″-di-O-trans-cinnamoyl)-α-l-rhamnopyranosylcatalpol and verbascoside: Cytotoxicity, cell cycle kinetics, apoptosis, and ROS production evaluation in tumor cells.

The aim of this study was to evaluate the impact that 6-O-(3″, 4″-di-O-trans-cinnamoyl)-α- l-rhamnopyranosylcatalpol (Dicinn) and verbascoside (Verb), two compounds simultaneously reported in Verbascum ovalifolium, have on tumor cell viability, apoptosis, cell cycle kinetics, and intracellular reactive oxygen species (ROS) level. At 100 µg/mL and 48 hours incubation time, Dicinn and Verb produced good cytotoxic effects in A549, HT-29, and MCF-7 cells. Dicinn induced cell-cycle arrest at the G0 /G1 phase and apoptosis, whereas Verb increased the population of subG1 cells and cell apoptosis rates. Furthermore, the two compounds exhibited time-dependent ROS generating effects in tumor cells (1-24 hours). Importantly, no cytotoxic effects were induced in nontumor MCF-10A cells by the two compounds up to 100 µg/mL. Overall, the effects exhibited by Verb in tumor cells were more potent, which can be correlated with its structural features, such as the presence of phenolic hydroxyl groups.

Ursolic acid derivative UA232 evokes apoptosis of lung cancer cells induced by endoplasmic reticulum stress

Context Ursolic acid (UA), a natural product, shows a broad spectrum of anticancer effects. However, the poor bioavailability and efficacy of UA limit its clinical application. Objective We developed novel analogues of UA with enhanced antitumor activities by the extensive chemical modification of UA. Materials and methods We developed multiple compounds by structural modification of UA, and found that UA232 had stronger activity than UA. The effects of UA232 (0–50 μM) on inhibiting the proliferation of A549 and H460 cells were determined by CCK-8 for 24, 48, or 72 h. The proapoptotic effect of UA232 was analyzed by microscopy and flow cytometry, and the potential signal pathway affected by UA232 was further validated by Western blotting and flow cytometry. Results Compared with UA, UA232 showed a stronger ability to inhibit the proliferation of lung cancer cells (IC50 = 5.4–6.1 μM for A549 and 3.9–5.7 μM for H460 cells). UA232 could induce not only cell cycle arrest in the G0/G1 phase but also apoptosis in both A549 and H460 cells. The treatment of UA232 could lead to an increase of CHOP expression rather than an increase in Bax or caspase-8, indicating that the apoptosis induced by UA232 was correlated with the endoplasmic reticulum stress (ER stress) pathway. Treatment with the ER stress-specific inhibitor, 4-PBA, decreased the ability of UA232 to induce apoptosis in A549 and H460 cells. Conclusion UA232 induced apoptosis through the ER stress pathway, and showed stronger growth-inhibitory effects in A549 and H460 cells compared to UA, which may be a potential anticancer drug to suppress the proliferation of lung cancer.

Interleukin-7 Resensitizes Non-Small-Cell Lung Cancer to Cisplatin via Inhibition of ABCG2.

Treatment with cisplatin (DDP) is one of the standard therapies used to treat non-small-cell lung cancer (NSCLC) and fundamentally causes resistance in cancer cells, which eventually poses as an obstacle to the efficacy of chemotherapy in NSCLC. Efforts are on all over the world to explore a sensitizer of NSCLC to DDP. Here, we studied the effect of IL-7 on the resistance of NSCLC to chemotherapy. We observed that IL-7 treatment significantly enhanced DDP-induced effects in A549 and A549/DDP cells (DDP-resistant cells), including decreased cell viability and proliferation, as well as increased cell apoptosis and S arrest, indicating that IL-7 treatment resensitized DDP-resistant NSCLC cells to DDP. Subsequently, IL-7 enhanced the sensitivity of PI3K/AKT signaling and expressions of ABCG2 to DDP. By inhibiting IL-7 signaling via IL-7R knockdown or activating PI3K/AKT signaling via PI3K activation, the resensitization to DDP by IL-7 was abrogated, and the expression levels of ABCG2, p-PI3K, and p-AKT were found to be significantly higher. In vivo results also confirmed that IL-7 only in combination with DDP could remarkably induce tumor regression with reduced levels of ABCG2 in tumorous tissues. These findings indicate that IL-7, apart from its adjuvant effect, could overcome multidrug resistance of DDP to restore its chemotherapy sensitivity.

Ruthenium(II)-Arene Thiocarboxylates: Identification of a Stable Dimer Selectively Cytotoxic to Invasive Breast Cancer Cells.

RuII -arene complexes provide a versatile scaffold for novel anticancer drugs. Seven new RuII -arene-thiocarboxylato dimers were synthesized and characterized. Three of the complexes (2 a, b and 5) showed promising antiproliferative activities in MDA-MB-231 (human invasive breast cancer) cells, and were further tested in a panel of fifteen cancerous and noncancerous cell lines. Complex 5 showed moderate but remarkably selective activity in MDA-MB-231 cells (IC50 =39±4 μm Ru). Real-time proliferation studies showed that 5 induced apoptosis in MDA-MB-231 cells but had no effect in A549 (human lung cancer, epithelial) cells. By contrast, 2 a and b showed moderate antiproliferative activity, but no apoptosis, in either cell line. Selective cytotoxicity of 5 in aggressive, mesenchymal-like MDA-MB-231 cells over many common epithelial cancer cell lines (including noninvasive breast cancer MCF-7) makes it an attractive lead compound for the development of specifically antimetastatic Ru complexes with low systemic toxicity.

Calotropis gigantea extract induces apoptosis through extrinsic/intrinsic pathways and reactive oxygen species generation in A549 and NCI-H1299 non-small cell lung cancer cells

BackgroundCalotropis gigantea (CG) is a tall and waxy flower that is used as a traditional remedy for fever, indigestion, rheumatism, leprosy, and leukoderma. However, the precise mechanisms of its anticancer effects have not yet been examined in human non-small cell lung cancer (NSCLC) cells. In this study, we investigated whether CG extract exerted an apoptotic effect in A549 and NCI-H1299 NSCLC cells.MethodsThe ethanol extract of CG was prepared, and its apoptotic effects on A549 and NCI-H1299 NSCLC cells were assessed by using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxy methoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, annexin V-fluorescein isothiocyanate/propidium iodide (PI) staining, cell cycle analysis, real-time polymerase chain reaction (RT-PCR), western blotting, JC-1 staining, and ROS detection assay.ResultsThe CG extract induced apoptosis through the stimulation of intrinsic and extrinsic signaling pathways in A549 and NCI-H1299 lung cancer cells. Cell cycle arrest was induced by the CG extract in both cell lines. Reactive oxygen species (ROS), which can induce cell death, were also generated in the CG-treated A549 and NCI-H1299 cells.ConclusionsThese data confirmed that CG caused apoptosis through the activation of extrinsic and intrinsic pathways, cell cycle arrest, and ROS generation in A549 and NCI-H1299 lung cancer cells. Thus, CG can be suggested as a potential agent for lung cancer therapy.

Inhibition of JAK2/STAT3 and activation of caspase‑9/3 are involved in KYS05090S‑induced apoptosis in ovarian cancer cells.

To overcome the poor prognosis of patients with ovarian cancer, attempting to target ovarian cancer with effective antitumor compounds has been conducted for numerous years. Although the 3,4‑dihydroquinazoline derivative KYS05090S was known to exert antitumor effects in A549 and ovarian cancer cells by inhibition of T‑type Ca2+ channels, the complete underlying antitumor mechanism of this compound remains unclear. Thus, in the present study, the potential apoptotic mechanism of KYS05090S was elucidated in SKOV3 and OVCAR3 ovarian cancer cells. KYS05090S exerted significant cytotoxicity in SKOV3 and OVCAR3 ovarian cancer cells, and also increased the number of apoptotic bodies, and the number of terminal deoxynucleotidyl transferase dUTP nick end labeling positive cells and the sub‑G1 population as a feature of apoptosis. Consistently, KYS05090S induced cleavage of poly(ADP‑ribose) polymerase and caspase‑9/3 in ovarian cancer cells. Notably, KYS05090S attenuated the expression of anti‑apoptotic proteins, including cyclinD1 and B‑cell lymphoma‑2(Bcl‑2), and reduced the phosphorylation of Janus kinase2(JAK2) and signal transducer and activator of transcription3 (STAT3) in ovarian cancer cells. Additionally, KYS05090S blocked the nuclear translocation of STAT3 and suppressed the signaling of JAK2/STAT3 in interleukin‑6‑treated SKOV3 cells, as a STAT3 activator. Overall, these observations indicated that inhibition of JAK2/STAT3 signaling and activation of caspase‑9/3 are critically involved in the effects of KYS05090S on apoptosis in ovarian cancer types, and the compound may be beneficial as a potent antitumor agent.

Mycosynthesis, characterization, anticancer and antibacterial activity of silver nanoparticles from endophytic fungus Talaromyces purpureogenus.

Background: Biogenic silver nanoparticles (AgNPs) have wider range of biomedical applications. The present work synthesized Tp-AgNPs using mycelial extract of endophytic fungus Talaromyces purpureogenus (MEEF), characterized, and analyzed for antibacterial, anti-proliferation and cell wounding healing activities.Methods: The synthesized Tp-AgNPs were characterized by UV-visible spectrophotometer (UV-Vis), field emission transmission electron microscopy (FETEM) with energy-dispersive X-ray spectroscopy (EDS), Fourier transform infrared spectroscopy (FTIR), particle size analysis (PSA) and X-ray diffraction (XRD). Further, antibacterial activity was determined by Kirby–Bauer test and anti-proliferation activity was tested in human lung carcinoma A549 by water-soluble tetrazolium and flow cytometer assay. In addition, cell wounding healing activity was determined by scratch assay.Results: UV-Vis results displayed a strong absorption peak from 390 nm to 420 nm, which indicated the successful synthesis of Tp-AgNPs. FETEM-EDS results indicated the round and triangle shaped Tp-AgNPs with the average size of 25 nm in accordance with PSA. FTIR analysis indicated the involvement of various functional molecules from MEEF in the synthesis of Tp-AgNPs. XRD result proved nature of Tp-AgNPs as a high-quality crystal. The Tp-AgNPs significantly inhibited the growth of bacterial pathogens at the minimal inhibitory concentration of 16.12 μg.mL−1 for Gram+, and 13.98 μg.mL−1 for Gram− bacteria. Further, Tp-AgNPs (2 μg.mL−1) showed a strong anti-proliferation effect in A549. Interestingly, Tp-AgNPs was not cytotoxic to normal NIH3T3 cells. In addition, the NPs exhibited a strong cell wounding healing activity.Conclusion: This work biosynthesized AgNPs with strong antibacterial, anticancer and cell wound healing properties using endophytic fungus T. purpureogenus.