Inhibited HeLa Cell Research Articles

Tin (IV) oxide (SnO2) nanoparticles inhibit the viability of cervical cancer HeLa cells through induction of apoptosis

Introduction: Resistance to chemotherapy and severe side effects have been reported as the main reasons for treatment failure in patients with cervical cancer. Therefore, it is necessary to find new treatment strategies with fewer side effects and more efficacy. This study aimed to investigate the cytotoxic property of tin (IV) oxide (SnO2) nanoparticles (NPs) against human cervical cancer cells (HeLa cells). In addition, the molecular mechanism of anticancer activity of SnO2 NPs was evaluated. Materials and Methods: The cytotoxicity of SnO2 NPs against HeLa cells and normal mouse fibroblast cells (L929) was studied using an MTT assay. To determine the mechanism of action of SnO2 NPs, the cells were treated with the half maximal inhibitory concentration values of SnO2 NPs for 24 h and apoptotic cell percentage was assessed by Annexin-PI and flow cytometry. In addition, real-time quantitative polymerase chain reaction (PCR) was used to evaluate the mRNA expression levels of apoptotic genes (Bax and Bcl-2). Results: SnO2 NPs suppress the viability of HeLa cells in a dose-dependent manner. This compound was more cytotoxic against HeLa cells than L929 cells. Flow-cytometry analysis revealed that SnO2 NPs significantly caused cell growth arrest. Moreover, real-time PCR results showed that SnO2 NPs treatment decreased Bcl-2 and increased Bax expression level. Conclusion: SnO2 NPs treatment significantly inhibit HeLa cells viability through the induction of apoptosis. Interestingly SnO2 NPs were more cytotoxic against HeLa cells than normal fibroblast cells, which may provide promising evidence for their applications as an anticancer drug.

Synthesis, anticancer activities and molecular modeling studies of some 2-aminonaphtho[2,3-d][1,3]thiazole-4,9-dione derivatives

Quinones, especially 1,4-naphthoquinones, are one of the most significant and widely distributed phytochemical groups in nature. 1,4-Naphthoquinones and their synthetic derivatives are found to possess remarkable cytotoxic activities. In this study, a series of 2-aminonaphtho[2,3-d][1,3]thiazole-4,9-dione derivatives were synthesized and their structures were verified with spectral analysis. In vitro cytotoxic activities of the synthesized compounds were evaluated by using MTT assay against MKN-45 (Human Gastric cancer), MDA-MB-231 (Human Breast cancer) and HeLa (Human Cervical cancer) cell lines. Among the synthesized compounds, 3d inhibited MDA-MB-cell proliferation with an IC50 value of 0.276 µM. Compound 3a inhibited HeLa and MKN-45 cell proliferation with IC50 values of 0.336 µM and 8.769 µM, respectively. Compound 3b inhibited HELA cell proliferation with an IC50 value of 0.269 µM. Molecular docking results suggest that the ligands may bind to the hDNA TopoIIβ binding pocket and partially exert their effects. These results propose that 2-aminonaphtho[2,3-d]thiazole-4,9-dion core has important biological effects and further explorations are worthwhile.

Gallic Acid Content and Antioxidant Activity of Pomegranate Peel Ethanol Extract

Ethanol extract of Pomegranate peel is proven to have the ability to inhibit the proliferation of cervical cancer HeLa cells. It was reported that this extract contains ellagic acid, gallic acid, and punicalagin which are identified as major effectors of antitumor activity. Gallic acid has been demonstrated to have an antioxidant activity that can influence cancer cell proliferation. The aim of the study was to identify the gallic acid content in pomegranate peel ethanol extract and to measure its antioxidant. This study was an experimental study performed at the Biochemistry and Molecular Biology Laboratory and Central Laboratory of Universitas Padjadjaran Bandung, Indonesia during September-December 2019. Gallic acid concentration was measured by using a high-performance liquid chromatography method (HPLC) and the antioxidant activity was measured by using 1,1-diphenyl-2-picrylhydrazyl (DPPH). The extract contained 616.97 mg/kg of gallic acid with an antioxidant activity of IC50 6.1 µg/mL. In conclusion, gallic acid has cytotoxic and antitumor effects from its ability to modulate antioxidant/pro-oxidant balance and inhibit reactive oxygen species (ROS). Therefore, both gallic acid content and antioxidant activity parameters can be used as markers in pomegranate peel extract which shows activities that inhibit HeLa cell proliferation.

Inhibition Capacity of the n-Hexane Fraction of Myrmecodia pendens as a Potential Anti-Cancer in Breast and Cervical Cancer: In Vitro Study

Breast cancer (BC) and cervical cancer (CC) have a high prevalence and mortality rate worldwide. Despite the availability of advanced treatment, resistance to conventional chemotherapies has emerged. Myrmecodia pendens, one of the species of Sarang Semut (local name), possess a potential of antitumor effects by inducing cell death different cancer cell entities. This study aimed to assess anti-tumor activities of n-hexane fraction of M. pendens in inhibiting cell survival and cell migration in BC and CC cells. M. pendens was extracted in methanol then fractionated using n-hexane or ethyl acetate. BC cells including MCF-7 (luminal A), HCC-1954 (HER2+) cells and CC Hela cells were treated with M. pendens extracts to evaluate cytotoxic activity using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay as well as anti-cell migration using scratch assay. We also analyzed inhibitory concentration 50 (IC50) of n-hexane fraction in BC and CC cells. We started with comparing cytotoxicity activities of methanol extract, ethyl acetate and n-hexane fractions of M. pendens. Data showed that the n-hexane fraction was the most potent inducing BC cell death. Therefore, we used the n-hexane fraction for further experiments. Interestingly, IC50 of this fraction in HCC-1954 and Hela cells were lower than in MCF-7 cells, 16; 13 and 60 ppm, respectively. Moreover, the low concentrations of n-hexane fraction inhibited HeLa cells migration, compared to control group (p<0.05). The n-hexane fraction of M. pendens shows promising anti-cancer agent, by inhibiting BC and CC cell survival as well as inhibiting CC cells migration.Keywords: breast cancer, cervical cancer, MTT assay, Sarang Semut, scratch assay

Ellagic acid inhibited cervical cancer growth via blocking the AKT/mTOR/STAT3 pathway

IntroductionEllagic acid (EA) is a kind of herb extract. However, the effects and mechanisms of EA in cervical cancer treatment are unclear.Material and methodsOur present work investigated the effects of EA on HeLa cervical cancer cell biological activities and relative mechanisms. Hela cells were divided into 5 groups as the NC group, Low group, Middle group, High group and 5-Fu group. MTT assay and cell apoptosis assay were performed to evaluate cell proliferation and apoptosis. Wound closure assay was used to assess the effect of EA on HeLa cell migration. We also assessed the anti-tumor effect of EA on a cervical tumor bearing BALB/c mouse model. Furthermore, western blotting and immunohistochemistry assay were performed to evaluate the effect of EA on the activation of AKT/mTOR/STAT3 in vitro and in vivo.ResultsThe cell experiments showed that EA had effects to inhibit Hela cell biological activities including cell apoptosis, migration and invasion dose-dependently and AKT, mTOR, and STAT3 phosphorylation expression levels were significantly depressed after EA supplementation in the in vitro study. In the in vivo study, EA significantly depressed tumor growth with cell apoptosis significantly increasing and the AKT/mTOR/STAT3 pathway was significantly down-regulated in tumor tissues.ConclusionsEA had anti-tumor effects on cervical cancer by depressing the AKT/mTOR/STAT3 pathway in in vitro and in vivo study.

Development of poly ADP-ribose polymerase-1 inhibitor with anti-cervical carcinoma activity

This research aimed to discover and identify new poly ADP-ribose polymerase-1 (PARP) inhibitors with potent anti-cervical carcinoma activity, and then explore their potential biological roles on cervical carcinoma cell. For this purpose, we identified a new PARP inhibitor from a high-throughput virtual screening method and found that the compound strongly inhibited cervical carcinoma HeLa cell. Cell proliferation was evaluated by an MTT assay, and the cell apoptosis was assessed by flow cytometry. Results showed that PARP1 is a poly ADP-ribose catalyzing enzyme in eukaryotic cells, which is activated during DNA damage and repair, and plays an important role in DNA repair and cell apoptosis. Herein we report the first discovery of a new PARP inhibitor from a high-throughput virtual screening method, then the compound was measured its anti-cervical carcinoma activity by using an MTT assay, which suggested that the compound strongly inhibited HeLa cell proliferation, the IC50 value is 0.65 µM. In addition, the compound induced HeLa cell apoptosis in a dose-response manner. All these data suggested that the compound is a promising lead compound, which deserves further investigation. It is concluded that the compound discover herein is a promising PARP-1 inhibitor with potent anti-cervical carcinoma activity, which deserves further investigation.

Epigallocatechin gallate inhibits HeLa cells by modulation of epigenetics and signaling pathways.

This study examines the effect of epigallocatechin gallate (EGCG) on signaling pathways, epigenetic modulators and tumour suppressor genes in cervical cancer cells, HeLa. qRT-PCR, ELISA-based enzymatic assays and in silico studies were used to catalogue the modulation of these genes by EGCG treatment. qRT-PCR showed transcriptional modulation of several epigenetic modifiers including DNA methyltransferases and histone modifiers (DNMT1, DNMT3B, DNMT3A, AURKA, AURKC, AURKB, KDM4A, KDM5C, PRMT7, PRMT6, UBE2B, HDAC5, HDAC6, HDAC7 and HDAC11. Furthermore, ELISA-based assays showed that EGCG lowered the activity of DNA methyltransferases, histone deacetylases and histone methyltransferases (H3K9). Molecular docking results suggests that EGCG may competitively inhibit some epigenetic enzymes (DNMT1, DNMT3A, HDAC2, HDAC3, HDAC4, HDAC7 and EZH2). A functional outcome of these epigenetic alterations could be inferred from the reversal of promoter hypermethylation of tumour suppressor genes by quantitative methylation array and transcriptional re-expression of tumour suppressor genes including TP73, PTEN, SOCS1, CDH1, RARβ, and DAPK1 by qRT-PCR. Downregulation of key signaling moieties of PI3K, Wnt and MAPK pathways, cell cycle regulators, metastasis regulators and pro-inflammatory moieties including TERT, CCNB1, CCNB2, MMP2, MMP7. PIK3C2B, PIK3CA, MAPK8 and IL6 was also observed. In silico protein-protein interaction network analysis followed by KEGG analysis discerned the active participation of gene sets towards cancer pathways. This study comprehensively explains EGCG's anti-cancer mechanism via thesynchronized transcriptional alteration ofseveral molecular targets across different signaling pathways and reversal of tumour suppressor gene silencing through modulation of epigenetic enzymes.

Ultrasound Microbubble-Mediated microRNA-505 Regulates Cervical Cancer Cell Growth via AKT2.

The application of ultrasound and microbubbles (USMB-) mediated microRNA (miR) is a promising approach of gene delivery for cancer treatment. We aimed to discuss the effects of USMB-miR-505 on cervical cancer (CC) development. miR-505 mediated by USMB was prepared. The effect of miR-505 on its transfection efficiency and the effect of miR-505 on HeLa cell proliferation, cell cycle, apoptosis, migration, and invasion were studied. The target gene of miR-505 was predicted, and its expression in CC was detected. The effect of the target gene on HeLa cells was further verified. USMB-miR-505 showed a higher transfection efficiency than miR-505 alone. The inhibitory effect of miR-505 mediated by USMB on HeLa cells was better than miR-505. miR-505 targeted AKT2, which was upregulated in CC. Overexpression of AKT2 reversed the inhibitory effect of USMB-miR-505 on HeLa cell malignant behaviors. Overall, we highlighted that USMB-miR-505 inhibited HeLa cell malignant behaviors by targeting AKT2.

Anticancer potentials of leaf, stem, and root extracts of Achyranthes aspera L.

Achyranthes aspera L. (Amaranthaceae), an herbaceous roadside weed in various parts of India, has several therapeutic uses, including the treatment against cancer. This investigation was undertaken to identify the bioactive compounds conferring cytotoxicity to the extracts from its biomass. The powdered leaf, stem, and root biomass was extracted separately in ethyl acetate, acetone, ethanol, and methanol. Each extract was tested against the HeLa cell line for the cytotoxicity, but the root-acetone extract was the most cytotoxic. This extract revealed eleven bands. The solution obtained from the ninth band (Rf = 0.87±0.06) exhibited more than 90% inhibition of HeLa cells. The LCMS analysis of this solution showed the presence of 37 compounds, out of which few compounds had been reported from different plants to possess cytotoxicity in various systems.

Ginsenoside Rh2 inhibits HeLa cell energy metabolism and induces apoptosis by upregulating voltage‑dependent anion channel 1.

20(S)-Ginsenoside Rh2 [20(S)-GRh2], one of the main active components of Panaxginseng, induces apoptosis in a wide range of cancer cell types. The present study found that 20(S)-GRh2 reduces mitochondrial membrane potential, decreases adenosine triphosphate generation and induces reactive oxygen species in HeLa cervical cancer cells. In addition, 20(S)-GRh2 activated mitochondrion-dependent apoptosis and inhibited both mitochondrial oxidative phosphorylation and glycolysis in HeLa cells. It was found that voltage-dependent anion channel 1 (VDAC1) expression was significantly upregulated by 20(S)-GRh2 treatment, while hexokinase 2 expression was downregulated and segregated from the mitochondria. Furthermore, 20(S)-GRh2 promoted Bax transport from the cytoplasm to the mitochondria, and knockdown of VDAC1 inhibited Bax transport and apoptosis. These results suggest that VDAC1 is a novel target of 20(S)-GRh2. The present study provides a better understanding of the mechanistic link between cervical cancer metabolism and growth control, and these results may facilitate the development of new treatments for cervical cancer.

LncRNA JPX promotes cervical cancer progression by modulating miR-25-3p/SOX4 axis

BackgroundThe long noncoding RNA (lncRNA) JPX is a molecular switch for X-chromosome inactivation. Accumulating studies have shown that the aberrant expression and function of lncRNAs are involved in the occurrence and development of tumors. However, the functional importance and mechanism of the action of lncRNA JPX in cervical cancer (CC) remain unknown.MethodIn this study, qRT-PCR and western blotting were used to evaluate the mRNA or protein expression of JPX, miR-25-3p and SOX4 in CC tissues and cell lines. StarBase v2.0 database, luciferase reporter assay and RNA immunoprecipitation assay were used to explore the relationship between JPX and miR-25-3p. EdU assay, CCK-8 assay and transwell assay were utilized to evaluate the proliferation, migration and invasion of CC cells. The tumor xenograft assay in nude mice was performed to demonstrate the role of the JPX/miR-25-3p/SOX4 axis in CC.ResultsWe found that JPX was markedly upregulated, whereas miR-25-3p was markedly downregulated in CC tissues and cell lines, and the expression of JPX was negatively correlated with miR-25-3p in CC tissues. Moreover, overexpression of JPX increased proliferation, migration and invasion of HeLa cells, whereas knockdown of JPX decreased proliferation, migration and invasion of HeLa cells. In contrast to JPX, overexpression of miR-25-3p decreased proliferation, migration and invasion of HeLa cells. In addition, knockdown of JPX was found to inhibit HeLa cell viability and tumor development via up-regulating the expression of miR-25-3p and inhibiting the expression of SOX4.ConclusionsOur study demonstrates that JPX promotes cervical cancer progression through modulating the miR-25-3p/SOX4 axis, and may serve as a potential target for CC therapy.

Leaf Extract of Nerium oleander L. Inhibits Cell Proliferation, Migration and Arrest of Cell Cycle at G2/M Phase in HeLa Cervical Cancer Cell.

Cervical cancer is one of the most common gynaecological malignant tumors reported in women. Although a number of early screening and treatment options are available, mortality due to cervical cancer remains high. Nerium oleander L. is a potential medicinal plant that possesses a wide spectrum of pharmacological and physiological activities including anticancer activities. This study aims to evaluate the antiproliferative activity, inhibition of cell migration and cell cycle arrest by the chloroform extract of leaves of Nerium Oleander L. in HeLa cervical cancer cells. The chloroform extract of Catharanthus roseus which contains anti-cancer compounds, Vinblastin and Vincristin, was used as a positive control for this study. The chloroform extracts of Nerium oleander L. and Catharanthus roseus were prepared using the standard protocol. The cytotoxic effects were studied by MTT assay. Cell migration was studied by in vitro scratch assay. Analysis of the cell cycle was carried out by Propidium iodide staining and Flow Cytometry. The expression level of various proteins was evaluated by immunocytochemistry. In this study, we showed that the leaf extract of Nerium oleander inhibited the growth of HeLa cervical cancer cells in culture and inhibited cell migration. Besides, it arrested the cell cycle at the G2/M phase. The Epidermal Growth Factor Receptor (EGFR) expression and phosphorylated p-Rb (Ser 780) level were significantly downregulated by leaf extract of Nerium oleander. The extract of Nerium oleander L. contains potential bioactive compounds that inhibit HeLa cell proliferation, cell migration and arrest cell cycle at the G2/M phase.

Host-Defense Peptides Caerin 1.1 and 1.9 Stimulate TNF-Alpha-Dependent Apoptotic Signals in Human Cervical Cancer HeLa Cells.

Host defense caerin 1.1 and 1.9 peptides, isolated from the glandular secretion of Australian tree frogs, the genus Litoria, have been previously shown to have multiple biological activities, including the inhibition of human papillomavirus (HPV) 16 early protein E7 transformed murine as well as human cancerous cell proliferation both in vitro and in vivo. However, the mechanism underlying their anti-proliferative activities against HPV18+ cervical cancer HeLa cells remains unknown. This study comparatively investigated the anti-proliferation on HeLa cells by caerin 1.1, 1.9, and their mixture, followed by confocal microscopy examination to assess the cellular intake of the peptides. Tandem mass tag labeling proteomics was employed to reveal the proteins that were significantly regulated by the peptide treatment in cells and cell growth environment, to elucidate the signaling pathways that were modulated. Western blot was performed to confirm the modulation of the pathways. Both caerin 1.1 and 1.9 highly inhibited HeLa cell proliferation with a significant additive effect compared to untreated and control peptide. They entered the cells with different magnitudes. Intensive protein-protein interaction was detected among significantly upregulated proteins. Translation, folding and localization of proteins and RNA processing, apoptosis process was significantly enriched post the treatments. The apoptotic signaling was suggested as a result of tumor necrosis factor-α (TNF-α) pathway activation, indicated by the dose-dependent elevated levels of caspase 3 and caspase 9. The epidermal growth factor receptor and androgen receptor pathways appeared inhibited by the peptides. Moreover, the activation of T-cell receptor derived from the quantitation results further implies the likelihood of recruiting more T cells to the cell growth environment post the treatment and more sensitive to T cell mediated killing of HeLa cells. Our results indicate that caerin 1.1 and 1.9 mediate apoptotic signals of HeLa cells and may subsequently enhances adaptive T cell immune responses.

Synthetic and antitumor comparison of 9-O-alkylated and carbohydrate-modified berberine derivatives

Berberine is a naturally occurring isoquinoline alkaloid with moderate antitumor effect. It has been proved that berberine can affect the microenvironment of cancer cells, which is critical for cancer therapy and improving human immunity. Therefore, structural modification of berberine to obtain derivatives with high antitumor effect attracts the great attention of scientists. This paper describes the synthesis and in vitro antitumor investigation of some 9-O-alkylated and carbohydrate-modified berberine derivatives using high efficient strategy. The cytotoxicity investigation was accomplished on different cancer cell lines by the well-optimized MTT assay, and the results indicated that 9-O-hydrophobic modified berberine derivative 9 with long lipid chain showed promising in vitro antitumor activity with the IC50 value as low as 4.87 ± 0.24 μM. Percentage of apoptosis was measured by a Hoechst 33342/PI staining strategy on HeLa cells, which revealed that compound 9 could induce 84% of cell apoptosis at very low concentration (5 μM). Flow cytometry analysis indicated that compound 9 might inhibit HeLa cell proliferation by G2 phase arrest. The expression of various cell apoptosis proteins was measured by western blot analysis, and the results indicated that compound 9 could induce over-expression of Caspase-3, Parp, and Bax and down-regulate the expression of P53 and PCNA. All these data indicated the high potential of compound 9 for developing novel anticancer drugs.

LncRNA EWSAT1 upregulates CPEB4 via miR-330-5p to promote cervical cancer development.

Long non-coding RNA (lncRNA) Ewing sarcoma associated transcript 1 (EWSAT1) is an oncogene in a variety of tumors. Here, we planned to demonstrate EWSAT1 function in cervical cancer and further illustrate its underlying mechanism. EWSAT1 expression in cervical cancer was evaluated through qRT-PCR. Colony forming capacity was measured by colony formation assay and cell proliferation ability was measured by CCK-8 kit. Wound healing experiment was applied to test the cell migration and transwell assay was applied to test the invasion ability. Luciferase assay was employed to demonstrate EWSAT1 and miR-330-5p interaction. In cervical cancer, the expression of EWSAT1 was enhanced and contributed to the poor prognosis. Downregulated EWSAT1 expression inhibited Hela cell migration, proliferation, and invasion. EWSAT1 targeted to miR-330-5p and upregulated cytoplasmic polyadenylation element-binding protein 4 (CPEB4) expression by sponging miR-330-5p. Our study revealed that EWSAT1 enhances CPEB4 expression through sponging miR-330-5p, thereby promoting cervical cancer development, which might provide potential therapeutic targets for clinically cervical cancer patients.

Resveratrol induces cervical cancer HeLa cell apoptosis through the activation and nuclear translocation promotion of FOXO3a.

Resveratrol (trans-3,4'V,5-trihydroxystilbene) presents antioxidant, anti-inflammatory, and cardioprotective functions in addition to its anticancer potential. In this study, we explored how resveratrol, as an anticancer agent, effectively influences cervical cancer HeLa cells. Our data showed that resveratrol could significantly inhibit HeLa cell proliferation and induce their apoptosis, as measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay and flow cytometry. The immunofluorescence staining results in the present study suggested that resveratrol could facilitate FOXO3a nuclear translocation. We then focused on the mechanism of resveratrol in promoting HeLa cell apoptosis. The following experiments suggested that the possible initial mechanism involves the upregulation Forkhead box O (FOXO) 3a expression, which further increases the expression of Bcl-2 interacting mediator of cell death (BIM), the gene transcribed in apoptosis. Resveratrol could also inactivate the basal extracellular signal-regulated kinase (ERK) activity, causing FOXO3a activation and resulting in HeLa cell apoptosis. In summary, both mechanisms stimulated the accumulation of activated FOXO3a, promoted its nuclear translocation, and ultimately caused HeLa cell apoptosis. Thus, resveratrol may have a potential in the treatment of cervical cancer.

Digitoxin inhibits HeLa cell growth through the induction of G2/M cell cycle arrest and apoptosis in vitro and in vivo.

Cervical cancer is the fourth most common gynecological malignancy affecting the health of women worldwide and the second most common cause of cancer‑related mortality among women in developing regions. Thus, the development of effective chemotherapeutic drugs for the treatment of cervical cancer has become an important issue in the medical field. The application of natural products for the prevention and treatment of various diseases, particularly cancer, has always attracted widespread attention. In the present study, a library of natural products composed of 78single compounds was screened and it was found that digitoxin exhibited the highest cytotoxicity against HeLa cervical cancer cells with an IC50 value of 28nM at 48h. Furthermore, digitoxin exhibited extensive antitumor activities in a variety of malignant cell lines, including the lung cancer cell line, A549, the hepatoma cell line, MHCC97H, and the colon cancer cell line, HCT116. Mechanistically, digitoxin caused DNA double‑stranded breaks (DSBs), inhibited the cell cycle at the G2/M phase via the ataxia telangiectasia mutated serine/threonine kinase (ATM)/ATM and Rad3‑related serine/threonine kinase (ATR)‑checkpoint kinase (CHK1)/checkpoint kinase 2 (CHK2)‑Cdc25C pathway and ultimately triggered mitochondrial apoptosis, which was characterized by the disruption of Bax/Bcl‑2, the release of cytochrome c and the sequential activation of caspases and poly(ADP‑ribose) polymerase(PARP). In addition, the invivo anticancer effect of digitoxin was confirmed in HeLa cell xenotransplantation models. On the whole, the findings of the present study demonstrate the efficacy of digitoxin against cervical cancer invivo and elucidate its molecular mechanisms, including DSBs, cell cycle arrest and mitochondrial apoptosis. These results will contribute to the development of digitoxin as a chemotherapeutic agent in the treatment of cervical cancer.

Blocking ACAT-1 Activity for Tumor Therapy with Fluorescent Hyperstar Polymer-Encapsulated Avasimible.

Targeting the distinct cholesterol metabolism of tumor cells is proposed as a novel way to treat tumors. Blocking acyl-CoA cholesterol acyltransferase-1 (ACAT-1) by the inhibitor avasimible (Ava), which elevates intracellular free cholesterol levels, is shown to effectively induce apoptosis. However, Ava faces disadvantages of poor water solubility, a short half-life, and no capability for fluorescence detection, which have greatly limited its application. Herein, a fluorescent hyperstar polymer (FHSP) is developed to encapsulate Ava to improve its ability to inhibit HeLa cells and K562 cells. The results of this study show that the obtained Ava-FHSP micelles possess a high drug loading capacity of 22.7% and bright green fluorescence. Ava and Ava-FHSP are cytotoxic to both HeLa and K562 cells and cause reductions in cell size, nuclear lysis, and chromatin condensation and hindered proliferation of both cell types by causing S phase cell cycle arrest. Further mechanistic analysis indicates that Ava-FHSP reduces the protein and messenger RNA expression of ACAT-1 and significantly increases intracellular free cholesterol levels, which can increase endoplasmic reticulum stress and finally cause cell apoptosis. All these results suggest that this fluorescent hyperstar polymer represents a potential therapeutic tumor strategy by changing the cholesterol metabolism of tumor cells.

Platelet-Membrane-Camouflaged Zirconia Nanoparticles Inhibit the Invasion and Metastasis of Hela Cells.

Zirconia nanoparticles (ZrO2 NPs) are widely applied in the field of biomedicine. In this study, we constructed a nanoplatform of ZrO2 NPs coated with a platelet membrane (PLTm), named PLT@ZrO2. PLTm nanovesicles camouflage ZrO2 NPs, prevent nanoparticles from being cleared by macrophage, and target tumor sites. Compared to ZrO2 alone, PLT@ZrO2 is better at inhibiting the invasion and metastasis of Hela cells in vitro and in vivo. In vitro, PLT@ZrO2 inhibited the growth and proliferation of Hela cells. Scratch-wound healing recovery assay demonstrated that PLT@ZrO2 inhibited Hela cells migration. Transwell migration and invasion assays showed that PLT@ZrO2 inhibited Hela cells migration and invasion. In vivo, PLT@ZrO2 inhibited the tumor growth of Xenograft mice and inhibited the lung and liver metastasis of Hela cells. Immunofluorescence and Western blotting results showed that anti-metastasis protein (E-cadherin) was upregulated and pro-metastasis proteins (N-cadherin, Smad4, Vimentin, E-cadherin,β-catenin, Fibronectin, Snail, Slug, MMP2, Smad2) were down-regulated. Our study indicated that PLT@ZrO2 significantly inhibits tumor growth, invasion, and metastasis.

The effect of carboxylated nanodiamonds on tumor cells migration

Nanodiamonds and their modified derivatives attract wide attention in medical application for their excellent therapeutic efficacy as drug delivery platforms and unique optical properties as imaging probes. However, besides the well acknowledged good biocompatibility, little is known about their influence on cell migration. In present work, the effect of carboxylated nanodiamonds (cNDs) on cell migration has been investigated. Two cancer cell lines (HeLa and C6) and two normal cell lines (MDCK and NIH/3T3) have been chosen as test cells. The cellular uptake process of cNDs has been visualized by 3D confocal Raman imaging after exposure to different concentrations of cNDs. cNDs show no apparent influence on cells viability up to a concentration of 200 μg/ml. Whereas, cNDs ≥100 μg/ml can inhibit HeLa cell migration and cNDs ≥25 μg/ml exhibit attenuated effect on C6 cell motility after co-cultured with cNDs for 24 h. Further mRNA studies indicate that cNDs with specific concentration downregulate the expression of vimentin in HeLa and C6 cells, which is responsible for cell contact formation, arrangement and transport of signal molecules in cancer metastasis. These results suggest that cNDs play an active role in regulating cancer cells migration besides act as drug carriers and imaging probes.