Inhibited Cancer Cell Colony Formation Research Articles

Sophaline B inhibits non-small cell lung cancer by activating NLRP3/caspase-1/GSDMD-dependent pyroptosis and PI3K/AKT/mTOR-mediated autophagy

Sophaline B (SPB), extracted from the seeds of Sophora alopecuroides L., is a natural bioactive compound that effectively exerts antiviral activities against the hepatitis B virus. This is the first study to demonstrate that SPB exerts anti-tumor effects on NSCLC by inducing pyroptosis and autophagy. SPB promotes NSCLC cell death by increasing the reactive oxygen species (ROS) production to induce pyroptosis via activating the NLRP3/Caspase-1/GSDMD signalling pathway. Meanwhile, SPB inhibits cancer cell proliferation by activating autophagy via blocking the PI3K/AKT/mTOR signalling pathway. Further investigation indicates that SPB inhibits NSCLC cell migration and invasion by increasing E-cadherin while decreasing N-cadherin, vimentin, and snail at the protein level. In addition, our results show that SPB inhibits cancer cell colony formation and human umbilical vein endothelial cell angiogenesis. Our study revealed the mechanisms of SPB triggering pyroptosis and autophagy in NSCLC, thus providing evidence and information on the SPB as an anti-cancer agent in NSCLC.

Sophflarine A, a novel matrine-derived alkaloid from Sophora flavescens with therapeutic potential for non-small cell lung cancer through ROS-mediated pyroptosis and autophagy

Novel compounds and more efficient treatment options are urgently needed for the treatment of non-small cell lung cancer (NSCLC). The decoction of Sophora flavescens has been used to treat NSCLC in the clinic, and matrine-type alkaloids are generally considered to be the key pharmacodynamic material basis. But the previous study showed that common matrine-type alkaloids exhibit significant cytotoxicity only when at concentrations close to the millimolar (mM) level. The key antitumor alkaloids in S. flavescens seem to have not yet been revealed. The aim of this study was to screen water-soluble matrine alkaloid with novel skeleton and enhanced activity from S. flavescens, and to reveal the pharmacological mechanism of its therapeutic effect on NSCLC. Alkaloid was obtained from S. flavescens by chromatographic separation methods. The structure of alkaloid was determined by spectroscopic methods, and single-crystal X-ray diffraction. The mechanism of anti-NSCLC in vitro with cellular models was evaluated by MTT assay, western blotting, cell migration and invasion assay, plate colony-formation assay, tube formation assay, immunohistochemistry assay, hematoxylin and eosin staining. The antitumor efficacy in vivo was test in NSCLC xenograft models. A novel water-soluble matrine-derived alkaloid incorporating 6/8/6/6 tetracyclic ring system, named sophflarine A (SFA), was isolated from the roots of S. flavescens. SFA had significantly enhanced cytotoxicity compared with the common matrine-type alkaloids, having an IC50 value of 11.3μM in A549 and 11.5μM in H820 cells at 48h. Mechanistically, SFA promoted NSCLC cell death by inducing pyroptosis via activating the NLRP3/caspase-1/GSDMD signaling pathway, and inhibited cancer cell proliferation by increasing the ROS production to activate autophagy via blocking the PI3K/AKT/mTOR signaling pathway. Additionally, SFA also inhibited NSCLC cell migration and invasion by suppressing EMT pathway, and inhibited cancer cell colony formation and human umbilical vein endothelial cell angiogenesis. In concordance with the above results, SFA treatment blocked tumor growth in an A549 cell-bearing orthotopic mouse model. This study revealed a potential therapeutic mechanism of a novel matrine-derived alkaloid, which not only described a rational explanation for the clinical utilization of S. flavescens, but also provided a potential candidate compound for NSCLC treatment.

Regulation of carcinogenesis and modulation through Wnt/\u03b2-catenin signaling by curcumin in an ovarian cancer cell line

The secreted frizzled-related protein 5 gene (SFRP5) that antagonize the Wnt/β-catenin signaling is frequently inactivated by promoter methylation and oncogenic activation of the Wnt signaling pathway is common in many cancers. The curcumin-rich Curcuma longa has been reported to potent anti-cancer property involved in epigenetic regulation to inhibit tumor suppressor gene methylation and re-expression. In a compounds screening, we found that curcumin can inhibit Wnt/β-catenin signaling. Therefore, the aim of this study was to investigate the effects of curcumin on SFRP5 DNA methylation modification in an ovarian cancer cell line (SKOV3). SKOV3 cells were treated with DMSO, 10 μM 5-aza-2′-deoxycytidine (DAC), 5 μM DAC, 20 μM curcumin, and 20 μM curcumin combined with 5 μM DAC for 96 hours, following which RNA and proteins were extracted for further analysis. The results showed that curcumin combined with 5 μM DAC may inhibit cancer cell colony formation, migration through EMT (epithelial–mesenchymal transition) process regulation, total DNMT activity, especially in DNMT3a protein expression, and may also regulate tumor suppressor gene SFRP5 expression involved in the Wnt/β-catenin signaling pathway. The combined treatment attenuated ovarian cancer development.

The regulation of curcumin on cacinogenesis and modulation through Wnt/β‐catenin signaling in ovarian cancer cell line

Ovarian cancer (OC) is the most lethal gynecologic malignancy and the top ten cancer of females in Taiwan and all over the world. Oncogenic activation of the Wnt signaling pathway is common in cancers, but mutation of beta‐catenin in ovarian cancer is rare. In addition to genetic events, epigenetic modification of secreted frizzled‐related protein (SFRP) family has been shown to be important in regulating Wnt signaling. The SFRPs act as antagonists of the Wnt ligands and inhibit the Wnt/β‐catenin signaling pathway. In the past research indicated the curcumin rich in curcuma longa has the capacity for anti‐ inflammatory, anti‐ oxidant and anti‐cancer effects as well as involve in the epigenetic regulation. It is helpful for inhibiting the tumor suppressor gene methylated and re‐expression. Therefore, the aim of this study is going to investigate the effects of curcumin on sFRP5 DNA methylation modification in ovarian cancer cell (SKOV3). Cell was treated with DMSO, 10 μM 5‐aza‐2′‐deoxycytidine (DAC), 5 μM DAC, 20 μM curcumin and respectively combined with 5 μM DAC in 96 hours, extracting the RNA and proteins for further analyze. The results of present study show that curcumin combined with 5 μM DAC may inhibit cancer cell colony formation and migration, the total DNMT activity, DNMT3a protein expression, also regulate tumor suppressor gene SFRP5 expression through Wnt/β‐catenin signaling pathway. As a result, it can attenuate or inhibit the ovarian cancer development.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Monanchoxymycalin C with anticancer properties, new analogue of crambescidin 800 from the marine sponge Monanchora pulchra

A new pentacyclic guanidine alkaloid, monanchoxymycalin C (1) was isolated from a new collection of marine sponge Monanchora pulchra along with the known monanchoxymycalin A (2). The structure of 1 was elucidated on the basis of spectroscopic data. Monanchoxymycalin C exhibits cytotoxic activity against human cancer HeLa cells at low micromolar concentrations, induces apoptosis-related death of malignant cells and inhibits cancer cell colony formation. In addition, synergistic and additive effects have been observed in combination with cisplatin.

Overexpression of WDFY2 inhibits prostate cancer cell growth and migration via inactivation of Akt pathway.

Prostate cancer is the most commonly diagnosed malignancy and is the second leading deadly reason among male cancer. WDFY2, which is found to be a cancer-specific fusion gene with CDKN2D in ovarian cancer, is a new gene with unknown function in carcinogenesis. In this study, we investigated the role of WDFY2 in prostate cancer development. We examined WDFY2 expression in human prostate tissue specimens and prostate cancer cell lines BPH-1, LNCaP, PC3, and DU-145. Overexpression of WDFY2 was performed to evaluate the role of WDFY2 in cell proliferation, migration, and colony formation of prostate cancer cells. We analyzed the clinical impact and prognosis of WDFY2 expression on the progress of prostate cancer through data from online datasets. Our results showed that WDFY2 had lower expression level in prostate tumors than in normal tissues. Overexpression of WDFY2 in prostate cancer cells DU145 and PC-3 led to the suppression of cancer cell migration and colony formation. Furthermore, we found that WDFY2 exerted its role by suppressing the activity of Akt pathway other than the epithelial-mesenchymal transition progression. In conclusion, we have uncovered WDFY2 as a tumor suppressor gene and a new potential biomarker for cancer progression. Our results showed that WDFY2 inhibited cancer cell colony formation and migration via suppressing Akt pathway, making it a potential new therapeutic target in prostate cancer.

Taraxerone triterpene inhibits cancer cell growth by inducing apoptosis in non-small cell lung cancer cells

<p class="Abstract">The objective of the present study was to evaluate the anti-cancer effects of taraxerone in non-small cell lung cancer cells (A-549). The effect of this compound on apoptosis and cellular morphology was also studied. MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay was used to evaluate the effect of the compound on cell viability. Cellular morphology after taraxerone treatment was demonstrated by fluorescence microscopy and transmission electron microscopy. The results revealed that taraxerone induced dose-dependent as well as time-dependent growth inhibitory effects on A-549 cell line showing an IC<sub>50</sub> value of 53.2 and 61.6 µM at 24 hours and 48 hours time intervals respectively. It also inhibited cancer cell colony formation in a dose-dependent manner and around 90% of the cancer cells were destroyed by the 125 µM dose of taraxerone treatment. Taraxerone also induced cell shrinkage, chromatin condensation and nuclear membrane rupture which are characteristic of apoptosis.</p><p> </p>