Proliferation Of Human Cancer Cells Research Articles

The V2 receptor antagonist tolvaptan counteracts proliferation and invasivity in human cancer cells

PurposeHyponatremia, the most frequent electrolyte alteration in clinical practice, has been associated with a worse prognosis in cancer patients. On the other hand, a better outcome has been related to serum sodium normalization. In vitro studies have shown that low extracellular sodium promotes cancer cells proliferation and invasiveness. Tolvaptan, a selective vasopressin receptor type 2 (V2) antagonist, has been effectively used in the last decade for the treatment of hyponatremia secondary to the Syndrome of Inappropriate Antidiuresis. A few in vitro data suggested a direct role of tolvaptan in counteracting cancer progression, so far. The aim of this study was to evaluate the effect and the mechanism of action of tolvaptan in cell lines from different tumours [i.e. colon cancer (HCT-8), hepatocarcinoma (HepG2), neuroblastoma (SK-N-AS)].Methods and resultsFirst, we showed that these cell lines express the V2 receptor. Tolvaptan significantly reduced cell proliferation with an IC50 in the micromolar range. Accordingly, reduced levels of cAMP, of the catalytic α subunit of PKA, and a reduced pAKT/AKT ratio were observed. Tolvaptan effectively inhibited cell cycle progression, whereas it induced apoptotis. Furthermore, it reduced cell invasiveness. In particular, anchorage-independent growth and the activity of collagenases type IV were blunted in the three cell lines. Accordingly, tolvaptan counteracted the RhoA/ROCK1–2 pathway, which has a pivotal role in regulating cell movement.ConclusionsOverall, these findings indicate that tolvaptan effectively inhibits tumour progression in vitro. Further studies should clarify whether the V2 receptor might be considered a possible target in anti-cancer strategies in the future.

Inhibitory Effect of Lotus Leaf-Enriched Flavonoid Extract on the Growth of HT-29 Colon Cancer Cells through the Expression of PI3K-Related Molecules.

Objectives Lotus leaf is rich in flavonoids, and this study is aimed at examining the inhibitory effect of lotus leaf-enriched flavonoid extract (LLEFE) on HT-29 colon cancer cells through phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) expression regulation. Methods Lotus leaves were extracted by ethanol and purified using FL-3 macroporous resin to create the LLEFE. HT-29 colon cancer cells were tested using various methods: their proliferation was observed by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, their survival status was observed by fluorescence staining, their oxidative stress level was observed by biochemical kits, and their mRNA expression was determined by quantitative polymerase chain reaction (qPCR) assay. Additionally, the composition of the flavonoids in lotus leaf was determined by HPLC. Results The results showed that the proliferation of NCM460 normal human colon cells was not affected by 0–500 μg/mL LLEFE but the proliferation of HT-29 human colon cancer cells decreased. LLEFE increased the LDH level in an HT-29 colon cancer cell culture medium; also increased the superoxide dismutase (SOD), catalase (CAT) activities, and glutathione (GSH) level in HT-29 cells; and decreased the malondialdehyde (MDA) level. Further experimental results showed that LLEFE upregulated the expression of SOD1, CAT, and GSH mRNA and downregulated the expression of PI3K, Akt, and mammalian target of rapamycin (mTOR) in HT-29 cells. The high-performance liquid chromatography (HPLC) results showed that kaempferin, hyperoside, astragaloside, phloridzin, and quercetin were the main chemical constituents of lotus leaf. Conclusion Lotus leaves contain functional flavonoids that inhibit the proliferation of HT-29 colon cancer cells and regulate the expression of PI3K/Akt through five important chemicals.

Amlodipine inhibits proliferation, invasion, and colony formation of breast cancer cells.

Calcium channel upregulation has been implicated in cancer cell proliferation and progression including in breast cancer. Fortunately, the function of calcium channels can be manipulated pharmacologically using calcium channel blockers (CCBs). Amlodipine, a dihydropyridine CCB, has been demonstrated to exert cytotoxic effects in several types of cancers. The present study evaluated the effects of amlodipine on proliferation, caspase activation, colony formation, and invasion of human breast cancer cells. Cell viability was assessed using a colorimetric MTT assay. An Apo-ONE® caspase-3/7 assay was used to measure caspase-3/7 levels. Cell invasion was evaluated using Matrigel invasion chambers. The expression of phospho-(p-)ERK1/2, Bcl-2, and integrin β1 proteins were analyzed using western blotting. A one-way ANOVA with a post-hoc Tukey's multiple comparison tests was used for statistical analysis. Amlodipine significantly inhibited the growth of both MDA-MB-231 and MCF-7 human breast cancer cells in a dose-dependent manner and inhibited colony formation of MCF-7 cells, and this was accompanied by the downregulation of p-ERK1/2 in MDA-MB-231 cells. In addition, treatment with amlodipine resulted in increased caspase-3/7 levels in MDA-MB-231 cells, which was accompanied by the downregulation of the anti-apoptotic protein, Bcl-2. Moreover, amlodipine impaired the invasive abilities of MDA-MB-231 cells, and integrin β1 expression was concurrently downregulated. The present study illustrates the anticancer effects of amlodipine on breast cancer proliferation, colony formation, and invasion in vitro and highlights the potential value of amlodipine as an anticancer agent.

Micro RNA Expression Profile Analysis in A549 Cancer Cells Treated with Methylsulfonylmethane

Clinical and Epidemiological studies have shown a correlation between Inflammation and lung cancer. Methylsulfonylmethane (MSM) has been used for years as a dietary supplement and clinical studies have shown MSM benefits for anti‐inflammation and prevention of stress of immune cells. In particular, these studies have shown that MSM potentially induces apoptosis in cancer cell lines, and prevents the spread of cancer cells. (Kang et al. 2017) However, the specific molecular control role that MSM plays has yet to be investigated. Experiments are in progress to determine if specific MicroRNA (miRNA) can be identified and shown to be significantly altered in presence of MSM. Identification and observation of miRNA have been of interest to our lab because of its key role in the regulation of gene expression. These small non‐coding bases are known to post‐transcriptionally fine‐tune up to 30% of genes and are currently implemented in cancer‐based therapy. Specific miRNA segments have been found to be up‐regulated and down‐regulated when cells start metastasis. Our lab is exploring the possible role that MSM plays in viability, cell proliferation, and possible molecular pathways of A549 human lung cancer cells in post MSM treatment. Our preliminary studies show that MSM concentrations from 100mM to 200mM are significantly effective for initiating apoptosis and inhibiting the proliferation of A549 cells without toxicity. The apoptotic pathway seems to be an intrinsic pathway based on the data gathered so far. Further studies will indicate if miRNA is a potential molecular player in the phenotypic changes of A549 exposed to MSM. As miRNA has been a growing therapeutic target for scientists it is hoped that if there is a link between MSM and miRNA down‐regulation, this might further solidify the value of nutraceutical studies in the treatment and control of cancer.

Preliminary Assessment of the Combination Studies of Artesunate with Paclitaxel on Human Prostate Cancer Cell Proliferation

Prostate cancer (PC) is the most common malignant cancer and the second leading cause of cancer‐related deaths in men. Approximately 18.9 out of 100,000 men per year die of prostate cancer. Common treatments such as androgen deprivation therapy (ADT,) surgical castration, and radiation therapy are used to counter PC; however, a proportion of patients relapse within a median of 2‐3 years with castration‐resistant prostate cancer (CRPC). In this study, combined effect of artesunate (ART) with paclitaxel (PTX) on human prostate cancer cell lines – LnCaP (androgen‐ dependent) and PC‐3 (androgen‐independent) were examined. In vitro anti‐proliferative (MTT) assay was used to assess the cytotoxic effects of ART, PTX, and in combination ratios 1:1, 1:2 and 2:1 on LnCaP and PC‐3 after 72‐ hour exposure. The IC50 values of 25.1 μM and 3.98 μM for ART and PXT on PC‐3 while the IC50 values of 2.13 μM and 0.05 μM on LnCaP were observed respectively. The average IC50 values when ART was combines with PXT were 0.499 μM and 0.084 μM on PC‐3 and LnCaP respectively. Overall, this study demonstrates that combining ART with PTX at different combination ratios has more effect on LnCaP than PC‐3 ‐ low IC50. In conclusion, combining ART with PTX displayed cytotoxicity regardless of the type of prostate cancer cell line. This may offer a promising new therapeutic option for the treatment of metastatic hormone‐refractory prostate cancer, aid in reducing cytotoxicity exerted by PTX alone and low prostate cancer mortality rate in men.

PEGylated palladium doped ceria oxide nanoparticles (Pd-dop-CeO2-PEG NPs) for inhibition of bacterial pathogens and human lung cancer cell proliferation

Antibacterial and anticancer activities of metallic nanoparticles are limited due to their instability and agglomeration. Therefore, we hypothesize that the coating of biocompatible polyethylene glycol (PEG) improves stability, prevents agglomeration, and enhance the prolongs blood circulation. Hence, this work reports the characterization, anticancer and antibacterial activities of Pd-dop-CeO2-PEG synthesized by Trichoderma extract (FE-En). The reduction of broad-spectrum intensity at 420 nm indicated the successful synthesis of Pd (2+) to Pd (0) NPs. The TEM results revealed that doping of CeO2 and PEG conjugation did not affect the morphology and dispersion of Pd NPs, Pd-dop-CeO2, and Pd-dop-CeO2-PEG. All three nanoparticles were polydispersed and spherical in shape. The sizes were 8.01 ± 2.46 nm for PdNPs, 9.02 ± 3.15 nm for Pd-dop-CeO2, and 12.95 ± 3.41 nm for Pd-dop-CeO2-PEG. The zeta potential was −29.9 ± 0.89 mV for Pd NPs, −38.9 ± 0.15 mV for Pd–CeO2 and - 42.2 ± 0.74 mV for Pd-dop-CeO2-PEG. FTIR results revealed the involvement of –OH and the amide group of FE-En in the synthesis of Pd (2+) ions to Pd (0) NPs. XRD analysis confirmed the crystalline structure of Pd NPs, Pd-dop- CeO2, and Pd-dop-CeO2-PEG. The Pd-dop-CeO2-PEG NPs were biocompatible with chick embryos and NIH3T3 cells. However, these NPs exhibited strong cytotoxicity to A549 cells with an IC50 of 81.25 ± 1.21 μg/mL for Pd-dop-CeO2-PEG, 118.75 ± 0.89 μg/mL for Pd-dop-CeO2, and 231.25 ± 2.08 μg/mL for PdNPs. Further, fluorescent staining results confirmed that the Pd-dop-CeO2-PEG induced cell death in A549 cells through cellular damage by oxidative stress. Also, Pd-dop-CeO2-PEG exhibited higher antibacterial activity against bacterial pathogens. Overall, these results confirmed the successful development of Pd-dop-CeO2-PEG as a promising anticancer and antibacterial agents.

Anticancer Activities of the Herbal Recipe Benjakul Extract against Human Breast Cancer Cells by Inducing Apoptosis and Suppressing Migration

Pharmacognosy Research,2022,14,2,115-120.DOI:10.5530/pres.14.2.16Published:April 2022Type:Original ArticleAuthors:Benjaporn Buranrat Author(s) affiliations:Benjaporn Buranrat Faculty of Medicine Program, Mahasarakham University, Muang District, Maha Sarakham, THAILAND. Abstract:Background: Benjakul is a Thai traditional formulation and has been reported for cancer treatment. Objectives: In this study aimed to examine the cytotoxic effects of Benjakul extract on suppression of breast cancer cells proliferation and migration. Materials and Methods: Cytotoxic effects were determined by sulforhodamine B, colony formation, ROS formation, caspase 3 activity, and mitochondrial function. Migration assay was studied by wound healing and gelatin zymography. Results: Piperine level was showed the highest concentration in the Benjakul extract. Further, Benjakul extract exhibited cytotoxicity against breast cancer cells with low IC50 equally effects in two cancer cells and further it suppressed the colony formation. The mechanism of Benjakul to induce cells death through activating ROS formation, stimulating caspase 3 activity, and repressing mitochondrial function. Moreover, the suppression of migration by Benjakul was acted on reduction of MMP-9 expression level in culture medium. Conclusion: Our findings demonstrated that Benjakul extract can suppress human cancer cells proliferation along with induction of apoptosis and attenuation of migration by low concentration. Key words: Benjakul, Breast cancer cells, Growth, Apoptosis, Migration. View:PDF (304.23 KB)

ATX/LPA axis regulates FAK activation, cell proliferation, apoptosis, and motility in human pancreatic cancer cells

ATX/LPA axis regulates FAK activation, cell proliferation, apoptosis, and motility in human pancreatic cancer cells

Inhibitory effect of lovastatin on human lung cancer cell proliferation by regulating the ERK1/2 and COX-2 pathways.

BackgroundLovastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, effectively inhibiting cholesterol synthesis. Previous research findings showed that lovastatin markedly suppressed tumor cell proliferation and metastasis and induced apoptosis. The present study aimed to determine the underlying mechanism of the suppressive effect of lovastatin on the growth of human lung cancer cells.MethodsThe A549 cell line was treated with different concentrations of lovastatin. Subsequently, cell proliferation and colony formation were analyzed, along with the expression of apoptosis-related proteins (ERK1/2, c-JUN, COX-2, BCL-2, and BAX) by western blotting and immunofluorescence staining. Experimental data were analyzed with SPSS 25.0 and expressed as the mean ± SEM. One-way ANOVA or two-way independent samples t-test were used.ResultsThe results confirmed that lovastatin suppressed cell viability and reduced the numbers of cell colonies, and a concentration-dependent response was observed with increasing lovastatin concentrations (P<0.05). Accordingly, these suppressive effects were related to decreased protein expression levels of p-ERK1/2/ERK1/2, p-c-JUN/c-JUN, COX-2, and BCL-2 and increased BAX protein expression (P<0.05). Furthermore, we conducted an experimental intervention with low-dose LPS+ATP to stimulate A549 cell growth, and then examined the proliferation and apoptosis of A549 cells after LPS+ATP+50 µM lovastatin intervention. The principal finding of this research was that lovastatin still suppressed A549 cell growth after LPS+ATP stimulation via modulation of ERK1/2, c-JUN, COX-2, BCL-2, and BAX protein levels (P<0.05).ConclusionsCollectively, the findings presented in this study confirmed that lovastatin can inhibit A549 cell proliferation by regulating the ERK1/2 and COX-2 pathways.

Effect of Tetrodotoxin on the Proliferation and Gene Expression of Human SW620 Colorectal Cancer Cells

Effect of Tetrodotoxin on the Proliferation and Gene Expression of Human SW620 Colorectal Cancer Cells

Induction of Bax and Activation of Caspases Hydro Ethanoic Leaf Extract of Citrullus colocynthis(L)- Mediated Apoptosis in Human Liver Cancer Cells Hep G2

Introduction: Citrullus colocynthis is a desert plant of the cucurbitaceae family. C. colocynthis grows in many countries with semi dry lands and that seeds are rich in oil which can encourage their sustainable agriculture to produce an economic biodiesel with a competitive price. Apoptosis, also termed as programmed cell death this is a key regulator of tissue homeostasis.&#x0D; Aim of the Study: To study the induction of bax and activation of caspases hydro ethanolic leaf extract of Citrullus colocynthis (L)- mediated apoptosis in human liver cancer cells Hep G2.&#x0D; Materials and Methods: In the present study, a human liver cancer cell line was procured from the National Centre for Cell science (NCCS), Pune, India. The cytotoxic potential of plant extract was analysed by MTG assay. mRNA expression of BaxmRNA and caspase-mRNA were analysed by Real-Time PCR using gene specific primers and a comparative CT method was used to analyse expression of genes. The data were analysed statistically using Graph pad prism software Version 5.&#x0D; Results: MTT analysis showed that Citrullus colocynthis a significant increase in proliferation of human liver cancer cells (P&lt;0.05) compared to untreated cells. However, 400 and 500 /g of the extract showed maximum effect in controlling cell growth. Results of the &lt;mRNA expression analysis showed that Citrullus colocynthis reduced the expression of BaxmRNA/ caspase-mRNA in human liver cancer cells at 400 and 500 /g (P&lt;0.05).&#x0D; Discussion: The anticancer effect of Citrullus colocynthis has been via a variety of pathways which includes apoptotic pathway, anti-inflammatory traits, and antioxidant pathway, etc [1]. Effect of HEAM on the mRNA level of tumor related genes (p53, Bcl-2), inflammatory (IL-1β, IL-6 and c-jun) and anti-inflammatory (IL-4) cytokines. Representative photographs of ethidium-bromide-stained 2% agarose gels for each gene after 7 months of treatment.&#x0D; Conclusion: The hydroethanolic leaf extract obtained from the Citrullus colocynthis exhibited anti-proliferative effect on human liver cancer cells HepG2 cell line by affecting the expression of the Bax mRNA and Bax mRNA and hindering the cell viability. Hence, it can be a great scope for using the extract into medicinal properties with further studies to improve herbal medicine for cancer over expensive drugs.

Dehydrocrenatidine Induces Liver Cancer Cell Apoptosis by Suppressing JNK-Mediated Signaling

Liver cancer is a leading cause of death worldwide. Despite advancement in therapeutic interventions, liver cancer is associated with poor prognosis because of highly lethal characteristics and high recurrence rate. In the present study, the anticancer potential of a plant-based alkaloid namely dehydrocrenatidine has been evaluated in human liver cancer cells. The study findings revealed that dehydrocrenatidine reduced cancer cell viability by arresting cell cycle at G2/M phase and activating mitochondria-mediated and death receptor-mediated apoptotic pathways. Specifically, dehydrocrenatidine significantly increased the expression of extrinsic pathway components (FAS, DR5, FADD, and TRADD) as well as intrinsic pathway components (Bax and Bim L/S) in liver cancer cells. In addition, dehydrocrenatidine significantly increased the cleavage and activation of PARP and caspases 3, 8, and 9. The analysis of upstream signaling pathways revealed that dehydrocrenatidine induced caspase-mediated apoptosis by suppressing the phosphorylation of JNK1/2. Taken together, the study identifies dehydrocrenatidine as a potent anticancer agent that can be use clinically to inhibit the proliferation of human liver cancer cells.

Elaeagnus angustifolia Plant Extract Induces Apoptosis via P53 and Signal Transducer and Activator of Transcription 3 Signaling Pathways in Triple-Negative Breast Cancer Cells.

Elaeagnus angustifolia (EA) is used as an alternative medicine in the Middle East to manage numerous human diseases. We recently reported that EA flower extract inhibits cell proliferation and invasion of human oral and HER2-positive breast cancer cells. Nevertheless, the outcome of EA extract on triple-negative breast cancer (TNBC) cells has not been explored yet. We herein investigate the effect of the aqueous EA extract (100 and 200 μl/ml) on two TNBC cell lines (MDA-MB-231 and MDA-MB-436) for 48 h and explore its underlying molecular pathways. Our data revealed that EA extract suppresses cell proliferation by approximately 50% and alters cell-cycle progression of these two cancer cell lines. Additionally, EA extract induces cell apoptosis by 40–50%, accompanied by the upregulation of pro-apoptotic markers (Bax and cleaved caspase-8) and downregulation of the anti-apoptotic marker, Bcl-2. Moreover, EA extract inhibits colony formation compared to their matched control. More significantly, the molecular pathway analysis of EA-treated cells revealed that EA extract enhances p53 expression, while inhibiting the expression of total and phosphorylated Signal Transducer and Activator Of Transcription 3 (STAT3) in both cell lines, suggesting p53 and STAT3 are the main key players behind the biological events provoked by the extract in TNBC cells. Our findings implicate that EA flower extract may possess an important potential as an anticancer drug against TNBC.

LINC-DUBR Suppresses Malignant Progression of Ovarian Cancer by Downregulating miR-107 to Induce SMAC Expression.

Background LINC-DUBR may be a potential therapeutic target in ovarian cancer (OC). The purpose of this research was to explore the impact of miR-107 on the tumorigenicity of OC and its underlying molecular mechanisms. Methods RT-qPCR was adopted to measure the expression of LINC-DUBR and miR-107 in ovarian cancer tissues and cells. CCK-8 assays and transwell chamber assays were conducted to evaluate the impacts of LINC-DUBR and miR-107 on the proliferation and invasion of human ovarian cancer cells (SKOV3). In addition, we determined the relationship between LINC-DUBR, miR-107, and SMAC using TargetScan and luciferase reporter assay. The protein expression of SMAC was determined by western blot. Results Compared with normal tissues and cells, LINC-DUBR was downregulated and miR-107 was highly expressed in ovarian cancer tissues and cell lines. Overexpression of LINC-DUBR inhibited the cell proliferation and invasive ability in OC cells SKOV3. The luciferase reporter assay proved overexpression of LINC-DUBR repressed cells proliferation and invasion via binding to miR-107 in ovarian cancer. In addition, we found that SMAC was downregulated directly by miR-107 in ovarian cancer. miR-107 mimic significantly increased cell proliferation and invasiveness of SKOV3, while overexpressed SMAC eliminated this effect. Furthermore, miR-107 could regulate the XIAP/caspase-3 signaling pathway in ovarian cancer by targeting SMAC. Conclusion LINC-DUBR suppressed malignant progression of ovarian cancer by downregulating miR-107 to induce SMAC expression and involving in the XIAP/caspase-3 signaling pathway.

Design, Synthesis, and Evaluation of Benzoheterocyclic-Containing Derivatives as Novel HDAC1 Inhibitors

In this study, the synthesis and biological evaluation of a variety of benzoheterocyclic-containing benzamide derivatives were described. Some of these compounds were proved to inhibiting the activity of histone deacetylase 1 (HDAC1) with IC50 values below the micromolar range, retarding proliferation of several human cancer cells, and surprisingly, not possessing toxicity to human normal cells and hERG K+ ion channels. Among those compounds, 3c was the most potent and efficacious derivative. Compound 3c was orally active and displayed excellent in vivo antitumor activity in a HCT-116 xenograft mice model.

The post-transcriptional inhibition of CXCR4 expression by miR-139 regulates the proliferation of human kidney cancer cells.

The C-X-C chemokine receptor 4 (CXCR4) has been reported to be involved in several cancer related processes. The current study was designed to investigate the role of CXCR4 in human kidney cancer and to unveil the underlying molecular mechanisms. The results showed the expression of CXCR4 to be significantly (P<0.05) upregulated in human renal cancer tissues and cell lines. Silencing of CXCR4 lead to a significant (P<0.05) decline of cell proliferation and colony formation of the Caki-1 and A498 kidney cancer cells. Moreover, the migration and invasion of the Caki-1 and A498 cells was also significantly (P<0.05) inhibited upon CXCR4 silencing. TargetScan analysis and dual luciferase assay revealed that CXCR4 interacts with microRNA-139 (miR-139). The expression of miR-139 was found to be significantly (P<0.05) downregulated in human kidney cancer cells lines. Overexpression of miR-139 caused post-transcriptional suppression of CXCR4 expression and significant (P<0.05) inhibition of the Caki-1 and A498 cell proliferation. Nonetheless, CXCR4 overexpression could nullify the inhibitory effects of miR-139 on the proliferation of Caki-1 and A498 cells. Taken together, the results revealed that CXCR/miR-139 axis regulates the proliferation, migration, and invasion of human kidney cancer cells and may act as a therapeutic target.

Biomass Accumulation of Gynostemma Pentaphyllum (Thunb.) Makino in Cell Suspension Cultures inhibiting Human Cancer Cell Growth

Gynostemma pentaphyllum (Thunb.) Makino (GpM) is a medicinal plant in traditional medicine throughout Asia for the treatment of several diseases including cancer. GpM plant cell suspension cultures provide a time and cost effective well-controlled means promising a high-yielding biomass production of pharmaceutical compounds. The purpose of the current work is to investigate the effect of GpM cell suspension cultures on human cancer cell lines growth. The biomass was produced by cell suspension culture of GpM callus into 250 mL Erlenmeyer flask containing 50 mL of liquid medium culture. Gypenosides in GpM were confirmed by HPLC. Pharmacological activities of GpM extract were tested on human cancer cell line (HepG2, Huh7, A549 and HL-60) using Sulforhodamine B (SRB) cytotoxicity assay and Tetrazolium (MTT) assay. We successfully produced 5.485 ± 0.223 g GpM fresh biomass per 250 mL Erlenmeyer flask after 18 days culture. Total gypenosides and Rb1 in dry cell suspension were 48.844 ± 3.933 mg/g and 0.041 ± 0.004 mg/g. The crude extract from GpM cell suspension cultures exhibited significant cancerous cell growth inhibition in a dose dependent manner. From the MTT assay and SRB cytotoxicity assay, it is obvious that GpM cell suspension culture extract at 200 μg/mL significantly inhibited the growth of multiple human cancer cells including hepatoma cell lines (HepG2, Huh7), lung carcinoma cell line (A549) and leukemia cell line (HL-60). Anti-cancer cell proliferation properties of GpM cell suspension culture were significantly higher than those of natural plants’ extracts. In this framework, GpM in cell suspension cultures was found to inhibit the proliferation of several human cancer cells. Biomass accumulation of GpM in cell suspension cultures may contribute to the development of efficient strategies for plant-derived anticancer compound production.

LINC00624/TEX10/NF-κB axis promotes proliferation and migration of human prostate cancer cells

Prostate cancer (PCa) is a malignant epithelial tumor with a high rate of biochemical or local recurrence. Studies have suggested that LINC00624 plays an important oncogenic role in liver cancer. However, whether it exerts similar effects in PCa progression remains unknown. In this study, we explored the effects of LINC00624 on the malignant progression of PCa and sought to identify the relevant signaling pathways. The results showed that LINC00624 was highly expressed in PCa tissues and cells and was associated with poor prognosis in PCa patients. In vitro and in vivo assays further showed that LINC00624 knockdown could decrease the proliferative and migratory ability of PCa cells. Mechanistically, we found that LINC00624 and TEX10 formed a co-regulatory axis that stimulated NF-κB activity. Our data suggest that LINC00624 acts as an oncogene in PCa progression and has potential as a novel biomarker for PCa.

Fatty Acid Binding Protein 6 Inhibition Decreases Cell Cycle Progression, Migration and Autophagy in Bladder Cancers.

Bladder cancer (BC) has a high recurrence rate worldwide. The aim of this study was to evaluate the role of fatty acid binding protein 6 (FABP6) in proliferation and migration in human bladder cancer cells. Cell growth was confirmed by MTT and colony formation assay. Western blotting was used to explore protein expressions. Wound healing and Transwell assays were performed to evaluate the migration ability. A xenograft animal model with subcutaneous implantation of BC cells was generated to confirm the tumor progression. Knockdown of FABP6 reduced cell growth in low-grade TSGH-8301 and high-grade T24 cells. Cell cycle blockade was observed with the decrease of CDK2, CDK4, and Ki67 levels in FABP6-knockdown BC cells. Interestingly, knockdown of FBAP6 led to downregulation of autophagic markers and activation of AKT-mTOR signaling. The application of PI3K/AKT inhibitor decreased cell viability mediated by FABP6-knockdown additionally. Moreover, FABP6-knockdown reduced peroxisome proliferator-activated receptor γ and retinoid X receptor α levels but increased p-p65 expression. Knockdown of FABP6 also inhibited BC cell motility with focal adhesive complex reduction. Finally, shFABP6 combined with cisplatin suppressed tumor growth in vivo. These results provide evidence that FABP6 may be a potential target in BC cells progression.

Characterization and biological activities of melanin pigment from root endophytic fungus, Phoma sp. RDSE17.

Melanins are high molecular weight hydrophobic pigments which have gained popularity for their role in virulence against different pathogens. In the present study, we isolated and characterized the melanin pigment produced by a dark septate endophyte fungus Phoma sp. RDSE17, which was associated with the roots of an indigenous Oryza sativa cv. 'Chakhao amubi' in Manipur, Northeast India. The biological properties of purified melanin from the fungus were evaluated for their antioxidant, antimicrobial and anticancerous activities. The pigment was extracted from Phoma sp. by alkaline-acid hydrolysis method and confirmed as melanin through physico-chemical tests and spectral (UV, FTIR, and EPR) analysis. The analyses of the elemental composition indicated that the pigment possessed a low percentage of nitrogen (N) contents, and therefore, would not fall under DOPA class of melanin. Exposure of the fungus to melanin pathway inhibitors revealed a positive melanin inhibition by tricyclazole, but not by kojic acid. Thus, the melanin from Phoma sp. may be a member of the DHN family. Moreover, the purified melanin showed high DPPH (1, 1-Diphenyl-2-picrylhydrazyl) free radical-scavenging activity with an EC50 of 69µg/mL and inhibited human lung cancer cell (A549 cells) proliferation at 80µg/mL. The present study demonstrates that melanin from Phoma sp. RDSE17 could be employed as a potential biological (antioxidant) and antimicrobial agent for inhibiting the growth of humans and phytopathogens.