Apoptosis In Cervical Cancer Cells Research Articles

MiR-205 Promotes Apoptosis of Cervical Cancer Cells and Enhances Drug Sensitivity of Cisplatin by Inhibiting YAP1.

Objective: Elevated expression of Yes-associated protein (YAP1) involves in the pathogenesis of cervical cancer. Bioinformatics analysis showed a targeting relationship between miR-205 and the 3'-UTR of YAP1. In this study, we aim to explore the role of miR-205 in the proliferation, apoptosis, or cisplatin (CDDP) resistance of cervical cancer cells. Patients and Methods: The dual luciferase reporter gene assay verified the relationship between miR-205 and YAP1. The CDDP-resistant cell line Hela/CDDP cells were cultured in vitro and divided into miR-NC group, miR-205 mimic group, and miR-205 inhibitor group followed by analysis of the expression of miR-205 and YAP1 mRNA by quantitative real-time polymerase chain reaction (qRT-PCR), and YAP1 protein level by western blot. Results: There was a targeted relationship between miR-205 and YAP1 mRNA. Compared with cervical cell line HCerEpiC cells, miR-205 expression was significantly decreased and YAP1 mRNA and protein expression was significantly increased in Hela cells (p < 0.01). Compared with miR-NC group, YAP1 protein expression in HeLa/CDDP cells was significantly decreased, cell apoptosis was increased, and proliferation was inhibited in miR-205 mimic-transfected Hela/CDDP cells (p < 0.01). Opposite results were obtained in miR-205 inhibitor-transfected Hela/CDDP cells. Conclusions: The expression of miR-205 is related to the CDDP resistance of cervical cancer cells. Increasing the expression of miR-205 can downregulate the expression of YAP1, inhibit the proliferation and promote apoptosis of cervical cancer cells, and enhance the sensitivity to CDDP.

MEG3 Induces Cervical Carcinoma Cells' Apoptosis Through Endoplasmic Reticulum Stress by miR-7-5p/STC1 Axis.

Background: Many patients with advanced cervical cancer (CC) have a poor prognosis and their mortality rank the first among women with malignant tumors. It's essential to explore the molecular mechanism of CC in clinical practice. Long noncoding RNA maternally expressed gene 3 (MEG3) has been reported to downregulate in CC tissues. However, the underlying mechanism of MEG3 in CC remains poorly elaborated. The current study aimed to explore the potential mechanism of MEG3 inducing endoplasmic reticulum stress (ERs)-mediated apoptosis of CC cells. Methods: The expression of MEG3 and miR-7-5p in CC tissues and cell lines was verified by quantitative reverse transcription/polymerase chain reaction (qRT-PCR). The vector of MEG3, miR-7-5p inhibitor, and sh-SCT1 were transfected into CC cell lines, and their expression was tested by qRT-PCR. Flow cytometry was used to detect apoptosis, and ERs-related protein expression was performed by Western blot. The regulatory relationship between MEG3/SCT1 and miR-7-5p was validated by Dual luciferase reporter assay. Results: CC tissues and cell lines showed downregulated MEG3 and STC1, and upregulated miR-7-5p. Overexpression of MEG3 or miR-7-5p inhibition induced ERs-triggered apoptosis of CC cells. In addition, sh-STC1 can reverse the effects of overexpressing MEG3 on CC cell apoptosis. In addition, dual luciferase reporter assay revealed that miR-7-5p can directly target to MEG3 and STC1. Conclusion: MEG3, act as a competing endogenous RNA of miR-7-5p, accelerates ERs-mediated apoptosis of CC cells through regulating SCT1 expression.

Achillea millefolium L. ethyl acetate fraction induces apoptosis and cell cycle arrest in human cervical cancer (HeLa) cells

This study aimed to develop a comprehensive quantification of 20 bioactive compounds in Achillea millefolium L (A. millefolium) fractions obtained by different solvents (petroleum ether (pet-ether), ethyl acetate (EtOAc), methanol (MeOH) and water) using HPLC quantitative analysis. Additionally, total flavonoids (TF), total phenolics (TP), antioxidants (DPPH, ABTS) and cytotoxic activities of A. millefolium fractions on k562, HeLa, MCF7, A431 and A549 Cell Lines were evaluated using MTT assay [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and compared to doxorubicin as a standard. According to the obtained results, TP ranged from 3.8 to 91.85 mg gallic acid equivalent (GAE)/g fraction, while TF ranged from 9.68 to 79.50 mg catechin equivalent (CE)/g generally. The lowest IC50 values were recorded for doxorubicin compared by all fractions except for EtOAc fraction against Hela cells, followed by water fraction, which showed the highest anticancer potential against MCF-7 cells. In contrast, the pet-ether fraction showed the lowest IC50 value against K562 cells. The cell cycle profile and apoptosis analysis of the EtOAc fraction was studied in HeLa cells. EtOAc fraction caused preG1 apoptosis and cell growth arrest in G2/M in HeLa cancer cells. Overall, this study heightens the importance of A. millefolium, which may be a promising and valuable source of natural antioxidant and anticancer agents to be used in the development of new functional and therapeutic compounds in the future.

RGMB-AS1/miR-4428/PBX1 axis drives the progression of cervical cancer.

BackgroundRGMB antisense RNA 1 (RGMB-AS1) is a member of long non-coding RNAs (lncRNAs) and relates to the carcinogenesis of numerous cancers. Nonetheless, its performance and mechanism in cervical cancer (CC) is unclear.MethodsThe expressions of RGMB-AS1, microRNA-4428 (miR-4428), PBX homeobox 1 (PBX1) were analyzed by quantitative real-time PCR (qRT-PCR). Nuclear-cytoplasmic fractionation was used to locate RGMB-AS1. Cell counting kit-8 (CCK-8), EdU, TUNEL, Western blot and transwell assays were performed to assess RGMB-AS1 function in proliferation, apoptosis, and invasion in vitro. Interplays involving miR-4428, RGMB-AS1 and PBX1 were verified applying luciferase reporter, RNA pull-down and RNA immunoprecipitation (RIP).ResultsRGMB-AS1 level was high in CC specimens and cells. RGMB-AS1 encouraged proliferation, and invasion, and depressed apoptosis in CC cells. Further, miR-4428 was screened as a targeted for RGMB-AS1, and RGMB-AS1 performed the competitive endogenous RNA (ceRNA) role to release PBX1 from miR-4428. Correlation analysis based on clinical specimens confirmed positive association between RGMB-AS1 and PBX1 and negative association of miR-4428 with RGMB-AS1 and PBX1. Rescue experiments indicated that PBX1 overexpression counteracted RGMB-AS1 silence-caused inhibition on CC development.ConclusionsRGMB-AS1 regulated miR-4428/PBX1 axis to aggravate CC development, indicating that targeting RGMB-AS1 could be a potent way for developing the novel therapeutic methods for CC patients.

SLC5A8 regulates the biological behaviors of cervical cancer cells through mediating the Wnt signaling pathway.

This study aims to investigate the role of solute transport family 5 member 8 (SLC5A8) in the progress of cervical cancer (CC) to provide a theoretical basis for the treatment of CC. Tissues were obtained from 58 patients diagnosed with CC in our hospital. Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) analysis was used to detect the expression level of SLC5A8 in CC tissues and cell lines. SLC5A8 level was up-regulated by transfection of SLC5A8 overexpression plasmid. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay and flow analysis were designed to measure the cell proliferation, cell cycle, and apoptosis of CC cells. The mRNA expression of SLC5A8 was down-regulated in CC tissues and cell lines. Transfection of SLC5A8 overexpression plasmid successfully over-expressed SLC5A8. In addition, an inhibited activation of Wnt signaling pathway was detected in CC cells after over-expression of SLC5A8. Besides, decreased proliferation activity and increased apoptosis were also observed in CC cells overexpressing SLC5A8 plasmid. Moreover, the impaired proliferation activity and increased apoptosis proportion of CC cells induced by SLC5A8 over-expression could be counteracted by the Wnt signaling pathway activator LiCl. SLC5A8 alleviates the progression of CC by regulating the Wnt signaling pathway.

LINP1 promotes the progression of cervical cancer by scaffolding EZH2, LSD1, and DNMT1 to inhibit the expression of KLF2 and PRSS8.

There is a growing body of evidence indicating that long non-coding RNAs (lncRNAs) are associated with a variety of cancers. LncRNA LINP1 has been shown to be a key factor in tumor malignancy. However, the role of LINP1 in cervical cancer (CC) it is unclear. In our research, we found that the levels of LINP1 were significantly elevated in CC tissues by comparison with adjacent normal tissue. Further, the expression level of LINP1 was upregulated in CC cells compared with healthy human cervical epithelial cell lines (HUCEC). Surprisingly, we found that downregulation of LINP1 significantly reduced the proliferation of CC cells and promoted apoptosis. Additionally, downregulation of LINP1 significantly decreased CC tumor growth in vivo. Further, we observed that LINP1 recruits EZH2, LSD1, and DNMT1, thereby reducing the expression of KLF2 and PRSS8. The results from our qRT-PCR analyses showed that silencing LINP1 uprgulated the expression of KLF2 and PRSS8 in CC cells. The results from our loss-of-function assays showed that upregulation of KLF2 and PRSS8 inhibits cell proliferation and boosts cell apoptosis in CC. We also found that inhibition of KLF2 and PRSS8 reversed the inhibitory effect on cell proliferation associated with silencing LINP1. In short, LINP1 facilitates the progression of CC by suppressing KLF2 and PRSS8, and thus could provide a promising target for CC therapy.

MiR-27a-3p Regulated the Aggressive Phenotypes of Cervical Cancer by Targeting FBXW7.

BackgroundAbnormally expressed microRNAs (miRNAs) contribute greatly to the initiation and development of human cancers, including cervical cancer, by regulating the target mRNAs. MiR-27a-3p was up-regulated and acted as an oncogene in multiple cancers. However, the function of miR-27a-3p in cervical cancer has not been fully understood.MethodsThe expression of miR-27a-3p in cervical cancer tissues and cell lines was detected by RT-pPCR. MTT assay, colony formation assay and flow cytometry analysis were performed to determine the effects of miR-27a-3p on the growth of cervical cancer cells. The targets of miR-27a-3p were predicted using the miRDB database. Luciferase reporter assay was utilized to confirm the binding between miR-27a-3p and the 3ʹ-untranslated region (UTR) of targets. The expression of target proteins was determined by RT-qPCR and Western blot.ResultsOur results found that miR-27a-3p was overexpressed in cervical cancer tissues and cell lines. Down-regulation of miR-27a-3p significantly inhibited the proliferation, colony formation and promoted apoptosis of cervical cancer cells. Overexpression of miR-27a-3p enhanced the cell proliferation. miR-27a-3p was found to bind the 3ʹ-UTR of F-box and WD repeat domain containing 7 (FBXW7) and resulted in the down-regulation of FBXW7. The up-regulated level of miR-27a-3p was inversely correlated with that of FBXW7 in cervical cancer tissues. Additionally, reintroducing of FBXW7 significantly attenuated the promoting effect of miR-27a-3p on the proliferation of cervical cancer cells.ConclusionThese results indicated the growth-promoting function of miR-27a-3p in cervical cancer via targeting FBXW7. Our finding suggested the potential application of miR-27a-3p/FBXW7 axis in the diagnosis and treatment of cervical cancer.

Cytotoxicity and Antioxidant Effects of Celastrus hindsii Benth. Leaf Extract

Celastrus hindsii Benth et Hook. is known as a herbal medicine for the treatment of cancer. In this study we evaluated the cytotoxic and antioxidant effects of Celastrus hindsii Benth et Hook. leaf extract. Samples of Celastrus hindsii were extracted with 90 % ethanol and subsequently fractionated with n-hexane, ethyl acetate (EtOAc) and n-butanol (n-BuOH) solvents. To evaluate the cytotoxic effect, we performed MTT (3- (4,5 dimethylthiazol-2 - yl) - 2,5 - diphenyltetrazolium) assay on the three cell lines human liver Hep G2 (HB - 8065TM), lung LU-1 (HTB - 57TM), breast MCF-7 (HTB - 22TM). The antioxidant effect was evaluated by screening DPPH (2,2-diphenyl-1-picryhydrazyl) free radical assay. The results showed that the EtOAc fraction had the strongest cytoxicity effects on liver cancer cells and lung cancer cells with an IC50 value of 33,7 ± 1,5 mg/mL and 13,0 ± 0,5 mg/mL. The BuOH fraction showed a weaker effect on lung cancer cells with IC50 value of 64,0 ± 2,2 mg/mL. The antioxidant results indicated that the EtOAc fraction had the best antioxidant effect with IC50 value of 46,9 ± 2,5 µg/mL. The EtOH total extract also has strong antioxidant activity with IC50 value of 48,5 ± 2,3 µg/mL. Our study showed that Celastrus hindsii leaf extract has the strong cytotoxicity and antioxidant activities.&#x0D; Keywords&#x0D; Celastrus hindsii Benth et Hook., cytotoxicity, MTT, antioxidant, DPPH.&#x0D; References&#x0D; [1] Ministry of health, General oncology. 2009: Vietnam Education Publishing House Limited Company, 9-10.[2] N.V. Tuyen, Pharmaceutical chemistry curriculum, 2014, Science and Technics Publishing House. 222-223.[3] V.V. Chi. Dictionary of Vietnamese medicinal plants. Medical Publishing House 1 (2012).[4] V. Gan, G. Chen, W. Zhang, J. Zhou . Oleanen induces apoptosis of cervical cancer cells by up-regulation of Bim. International Journal of Gynecologic Cancer 22(1) (2012) 38.[5] Y.H. Kuo, L.M.Y. Kuo. Antitumour and anti-AIDS triterpenes from Celastrus hindsii. Phytochemistry 44(7) (1997) 1275.[6] T. Mosmann, Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays 65(1-2) (1983) 55.[7] P. Mahakunakorn, M. Tohda, Y. Murakami, K. Matsumoto, H.J.B. Watanabe, P. Bulletin, Antioxidant and free radical-scavenging activity of Choto-san and its related constituents 27(1) (2004) 38.[8] P.T. Thuong, M.K. Na, N.H. Dang, T.M. Hung, P.T. Ky, T.V. Thanh, et al. Antioxidant activities of Vietnamese medicinal plants 12(1) (2006) 29.[9] X.Q. Hu, W. Han, Z.Z. Han, Q.X. Li, X.K. Xu, P. Fu, et al. A new macrocyclic lactone and a new quinoflavan from Celastrus hindsii. Phytochemistry letters 7 (2014) 169.[10] A.C. Spivey, M. Weston, Woodhead SJCSR. Celastraceae sesquiterpenoids: biological activity and synthesis 31(1) (2002) 43.[11] T.L. Ngoc, Technology. Separation process of rosmarinic acid and their derivatives from Celastrus hindsii benth leaves. Vietnam Journal of Science 54(2C) (2016) 380.[12] F.R. Mowsumi, A. Rahaman, N.C. Sarker, B.K. Choudhury, Hossain SJWJPPS. In vitro relative free radical scavenging effects of Calocybe indica (milky oyster) and Pleurotus djamor (pink oyster). 4(07) (2015).[13] T.D. Viet, T.D. Xuan, T.M. Van, Y. Andriana, R. Rayee, H.D. Tran. Comprehensive Fractionation of Antioxidants and GC-MS and ESI-MS Fingerprints of Celastrus hindsii Leaves. Medicines 6(2) (2019) 64.[14] T.N. Ly, M. Shimoyamada, Yamauchi RJJoa, chemistry f. Isolation and characterization of rosmarinic acid oligomers in Celastrus hindsii Benth leaves and their antioxidative activity 54(11) (2006) 3786.&#x0D; &#x0D;

HPV-mediated nuclear export of HP1\u03b3 drives cervical tumorigenesis by downregulation of p53

E6 oncoprotein derived from high-risk human papillomavirus (HPV) drives the development of cervical cancer through p53 degradation. Because cervical cancer therapies to inactivate HPV or E6 protein are not available, alternative strategies are required. Here, we show that HPV-mediated nuclear export of human heterochromatin protein 1γ (HP1γ) reduces the stability of p53 through UBE2L3-mediated p53 polyubiquitination during cervical cancer progression. In general, HP1 plays a key role in heterochromatin formation and transcription in the nucleus. However, our immunostaining data showed that the majority of HP1γ is localized in the cytoplasm in HPV-mediated cervical cancer. We found that HPV E6 protein drives unusual nuclear export of HP1γ through the interaction between the NES sequence of HP1γ and exportin-1. The mutation of the NES sequence in HP1γ led to nuclear retention of HP1γ and reduced cervical cancer cell growth and tumor generation. We further discovered that HP1γ directly suppresses the expression of UBE2L3 which drives E6-mediated proteasomal degradation of p53 in cervical cancer. Downregulation of UBE2L3 by overexpression of HP1γ suppressed UBE2L3-dependent p53 degradation-promoting apoptosis of cervical cancer cells. Our findings propose a useful strategy to overcome p53 degradation in cervical cancer through the blockage of nuclear export of HP1γ.

MiR-520d-5p functions as a tumor-suppressor gene in cervical cancer through targeting PTK2

ObjectivePTK2 has been reported to be involved in tumor progression, but its regulating mechanisms in cervical cancer (CC) remain to be elusive. MiRNA-520d-5p was demonstrated to regulate the expression of many genes and inhibit the development of human tumors. However, the functional mechanisms of miRNA-520d-5p in the regulation of cervical cancer are not fully understood. MethodsRT-qPCR was employed to detect the expression levels of miR-520d-5p and PTK2. Western blot was performed to detect the expression levels of proteins. Dual-luciferase reporter assay was utilized to investigate the associations between miR-520d-5p and PTK2. CCK-8 assay was carried out to measure cell proliferation. In addition, transwell assay and scratch assay were used for cell invasion and migration analysis. Flow cytometry was used to detect cell apoptosis of cervical cancer. ResultsThe expression levels of PTK2 were elevated in CC tissues and cells lines. It was found that PTK2 was a target gene of miR-520d-5p. The expression of miR-520d-5p was down-regulated in CC tissues, which was negatively correlated with the expression of PTK2. MiR-520d-5p inhibited the proliferation, migration, and invasion of CC cells. In addition, overexpression of miR-520d-5p resulted in apoptosis of CC cells. Finally, we demonstrated that miR-520d-5p inhibited the activation of PI3K/AKT signaling. ConclusionMiR-520d-5p suppressed the proliferation, invasion, and migration of CC cells via targeting PTK2.

Filamin B extensively regulates transcription and alternative splicing, and is associated with apoptosis in HeLa cells.

Post-transcriptional mechanisms are an important approach in the treatment of cancer, and may also be hijacked by tumor cells to help adapt to the local microenvironment. Filamin B (FLNB), an actin-binding protein that provides crucial scaffolds for cell motility and signaling, has also been identified as an RNA-binding protein. Recent studies demonstrated that FLNB might play an important role, not only in skeletal development, but also in regulating tumorigenesis; however, the effects of dysregulated expression of FLNB at the molecular level are not clear. In the present study, RNA-sequencing was performed to analyze changes in overall transcriptional and alternative splicing between the knocked-down FLNB and the control in HeLa cells. Decreased FLNB levels resulted in significantly lower apoptosis compared with control cells. FLNB knockdown extensively regulated the expression of genes in cell apoptosis, tumorigenesis, metastases, transmembrane transport and cartilage development. Moreover, FLNB regulated alternative splicing of a large number of genes involved in ‘cell death’ and the ‘apoptotic process’. Some genes and alternative splicing related to skeletal development were enriched and regulated by FLNB. Reverse transcription-quantitative-PCR identified FLNB-regulated transcription and alternative splicing of genes, such as NLR family apoptosis inhibitory protein, interleukin 23 subunit α, metastasis associated lung adenocarcinoma transcript 1, phosphofurin acidic cluster sorting protein 2, bone morphogenetic protein 7, matrix metallopeptidase 13, collagen type II α 1 chain, fibroblast growth factor receptor 2 and vitamin D receptor. The present study is the first study, to the best of the authors’ knowledge, to provide transcriptome-wide analysis of differential gene expression and alternative splicing upon FLNB silencing. The present results suggested that FLNB may play an important regulatory role in cervical cancer cell apoptosis via regulation of transcription and alternative splicing, which provide insight for the current understanding of the mechanisms of FLNB-mediated gene regulation.

Punicalagin promotes the apoptosis in human cervical cancer (ME-180) cells through mitochondrial pathway and by inhibiting the NF-kB signaling pathway

Increasing attention of plant derived therapeutic agents against cancer, investigating the anti-proliferative efficiency of plant derived chemicals have achieved increasing momentum for the design of anticancer drug. Punicalagin, dietary phytochemical altered the various cell signal transduction pathways associated with cell apoptosis and proliferation. This investigation was intended to examine the efficiency of punicalagin lying on cell viability so as to examine the molecular based punicalagin mechanism stimulated apoptosis via exploring the expression of Bcl-2 family proteins, and caspases also the cell cycle regulatory proteins p53 and NF-κB signaling in human cervical cancer cells. We also analyzed the morphological characteristic changes through mitochondrial membrane depolarization, reactive oxygen species (ROS) generation, TUNEL assay, AO/EtBr analysis in cervical cancer cells. Our findings demonstrated that punicalagin repressed the viability of cervical cancer cells in a dosereliant mode via stimulating mitochondrial mediated apoptosis. Moreover, our this study demonstrated that punicalagin blocked cervical cancer cell proliferation and stimulated cell apoptosis by suppressing NF-kappa B activity. Hence our study suggested that punicalagin exhibits opposing actions on NF-kappa B signaling networks to block cancer cell progression acts as a classical candidate for anticancer drug designing.

Elevation of microRNA-512-5p inhibits MUC1 to reduce radioresistance in cervical cancer

ABSTRACT Researches about the role of several microRNAs (miRNAs) in cervical cancer were performed by previous studies, but the function of miR-512-5p in cervical cancer is rare to see. Thus, we aimed to investigate the effect and mechanism of miR-512-5p on radiosensitivity in cervical cancer by regulating MUC1 expression. First, 111 patients with cervical cancer were divided into radiotherapy sensitive group and radiotherapy resistant group. After that, miR-512-5p expression in cancer tissues from two groups was detected. Next, RT-qPCR was used to detect miR-512-5p expression in radiotherapy resistant cervical cancer cells SiHa and radiotherapy sensitive cervical cancer cells Me180. Moreover, SiHa and Me180 cells were treated with miR-512-5p overexpression and MUC1 poor expression plasmids. With 0 Gy, 2 Gy, 4 Gy, 6 Gy and 8 Gy irradiation, proliferation, colony formation ability and apoptosis of cervical cancer cells were determined. Also, cell lines that overexpressed miR-512-5p and overexpressed MUC1 were then constructed to observe the changes in cell radiosensitivity. MiR-512-5p was down-regulated and MUC1 was up-regulated in radiotherapy resistant cervical cancer tissues and cells. Overexpression of miR-512-5p and down-regulation of MUC1 increased the apoptosis and reduced cell survival rate of cervical cancer cells after radiotherapy. Overexpression of miR-512-5p reversed the effect of MUC1 overexpression on decreasing cell apoptosis and elevating cell survival rate of cervical cancer cells. Our study provides evidence that elevation of miR-512-5p contributes to the reduction of radioresistance in cervical cancer cells by inhibiting MUC1 expression.

Cytotoxic and Apoptotic Induction Potential of Extracts from Fermented Citrullus vulgaris Thunb. Seeds on Cervical and Liver Cancer Cells

The anti-cancer activities of many fermented foods and beverages are now scientifically established. Ogiri-egusi is a condiment prepared from fermentation of Citrullus vulgaris (melon) seeds and consumed in many countries of West Africa. Its anti-oxidative and anti-hyperlipidaemic properties have been reported. This study investigated the anti-cancer activities of the aqueous and methanolic extracts from ogiri-egusi. Cytotoxicity was investigated using the MTT and colony-formation inhibition assays while flow-cytometer based Apopercentage assay was used to quantify apoptosis in extracts-treated cervical and liver cancer and normal human fibroblast cells. The inhibitory concentration responsible for killing 50% of cells after 24 h by the aqueous extract in KMST-6, HeLa, and Hep-G2 cells were estimated at 1.610, 1.020, and 1.507 mg/mL respectively. While these values reduced with increasing incubation time in cancer cells it increased in the non-cancer cell. Furthermore, the extract significantly induced apoptosis in HeLa (97 ± 0.18%) and Hep-G2 (73 ± 6.73%) cells. These findings were corroborated by cells morphologic presentations and inhibition of colony formation assay. These findings suggest that the aqueous extract from fermented Citrullus vulgaris seeds might be a nutraceutical with potential anti-cancer properties.

Vorinostat upregulates MICA via the PI3K/Akt pathway to enhance the ability of natural killer cells to kill tumor cells

Vorinostat has good therapeutic efficacy against primary cutaneous T-cell lymphoma in the refractory stage. However, the molecular mechanism by which it inhibits solid tumors has not been clarified. To investigate the tumor inhibitory mechanism of vorinostat in cervical cancer, this study used Cell Counting Kit-8, flow cytometry, cell invasion and migration assays and the wound healing assay to evaluate the effects of vorinostat on cervical cancer cell proliferation, apoptosis, cell cycle, migration, and invasion. Real-time quantitative PCR and immunoblotting were used to detect gene and protein expression, respectively, of major histocompatibility class I-related chain A, phosphoinositide 3-kinase, phosphorylated PI3K p55 (Tyr199), and p-Akt (Ser473). The lactate dehydrogenase cytotoxicity assay was used to evaluate the ability of natural killer-92 cells to lyse cervical cancer cells. A xenograft nude mouse model was established to analyze the anti-tumor effect of vorinostat in vivo. Our results showed that vorinostat inhibited the proliferation, migration, and invasion of cervical cancer cells. Vorinostat also induced apoptosis and cell-cycle arrest in the S phase, inhibited PI3K (p110α), p-PI3K p55 (Tyr199), and p-Akt (Ser473) protein expression and upregulated MICA expression in vitro and in vivo, and promoted NK-92 cell-mediated cervical cancer cell lysis. The ability of vorinostat to upregulate MICA expression in cervical cancer cells was related to PI3K/Akt signaling. In brief, vorinostat upregulated MICA through the PI3K/Akt pathway and enhanced the sensitivity of cervical cancer cells to the NK cell-mediated cytolytic reaction. The results of this study demonstrate that vorinostat has anti-solid tumor effects on cervical cancer.

N,P-Doped Carbon Nanodots for Food-Matrix Decontamination, Anticancer Potential, and Cellular Bio-Imaging Applications.

We report a facile one-step thermal treatment method for the synthesis of biocompatible, fluorescent nitrogen-phosphorus-doped carbon nanodots (NPCDs) as multifunctional agents for the food matrix decontamination, cancer targeting, and cellular bio-imaging. NPCDs exhibit high toxicity towards L. monocytogenes, as illustrated by fluorescent live-dead cell counting, disruption of membrane permeability/potential, changes in the levels of cellular ions, genetic materials, and proteins, as well as intracellular production of reactive oxygen species. The tryptophan and protein peaks released in NPCDs treated cells contributed to indole ring breathing and correlated with induced cell death. NPCDs significantly inhibited bacterial biofilm formation on a solid substrate. NPCDs-coated low-density polyethylene (LDPE) film crosslinked with 1% aminopropyltriethoxy silane (APTES) via silane-hydroxyl linking as a food-grade wrap significantly reduced bacterial counts in a raw chicken food model. Furthermore, NPCDs induced apoptosis in HeLa cervical cancer cells, as confirmed by the distorted cell morphology, fluorescence microscopic analysis, presence of fragmented nuclei and the qPCR results of mRNA expression levels of apoptotic markers. Moreover, NPCDs were also applicable in utilized for the cellular bio-imaging of KM12-C colon cancer cells under confocal microscopy owing to their excellent luminescence properties. Overall, NPCDs represent a promising platform to reduce the environmental health risks associated with hazardous pathogens, anticancer targeting, and their application in cellular bio-imaging as multifunctional targets/nanocarriers.

SNRPB promotes cervical cancer progression through repressing p53 expression

Cervical cancer is still a leading cause of tumor death in women across the world. Small nuclear ribonucleoprotein polypeptides B and B1 (SNRPB) gene encodes the components of the core spliceosomal machinery, and regulates the development of several types of cancers. However, its function in cervical cancer progression remains unclear. In the study, we found that SNRPB was highly expressed in human cervical cancer tissues and in cervical cancer cell lines. Meanwhile, SNRPB knockdown using shRNA in cervical cancer cells markedly reduced the cell proliferation, migration and invasion. Furthermore, the increased percentage of cells in G2/M phase and apoptotic cell death was detected in cervical cancer cells with SNRPB knockdown, suggesting that SNRPB might contribute to cervical cancer growth. Moreover, we found that SNRPB could directly interact with p53, and the interaction showed an essential role in modulating cervical cancer cell proliferation, migration, invasion and apoptosis. In xenograft model, the knockdown of SNRPB exerted effectively anti-cervical cancer ability characterized by the reduced tumor volume and weight, and a remarkable reduction in KI-67 expression. Improved expression of p53 validated the in vitro findings. Therefore, SNRPB might be a potent therapeutic target in cervical cancer through interacting with p53.

Biosynthesis of hematite nanoparticles using Rheum emodi and their antimicrobial and anticancerous effects in vitro

The synthesis of magnetic Hematite nanoparticles (α-Fe2O3) via green route has been a long lasting challenge for the scientific and technological fascination of many researchers. In the present investigation, iron oxide nanoparticles (α-Fe2O3) were synthesized using Rheum emodi roots in a cost effective and ecofriendly method. Their physicochemical property orchestration involved techniques such as UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), Transmission electron microscopy (TEM), Field emission scanning electron microscopy (FESEM), Energy-dispersive X-ray (EDX), X-ray diffraction (XRD), Thermogravimetric Analysis (TGA), Vibrating sample magnetometer (VSM), and Atomic force microscopy (AFM). Through TEM, FESEM and AFM analysis, α-Fe2O3NPs were confirmed spherical in shape and the average diameter of particle is ~12 nm as depicted through TEM image. Thermal property was investigated by TGA. Magnetic behavior was observed in R. emodi mediated α-Fe2O3NPs by magnetic hysteresis measurements. FTIR analysis revealed the presence of anthraquinones in R. emodi roots extract which play the central role in stabilization of the α-Fe2O3NPs. Further, the crystalline nature of the nanoparticle sample was determined with XRD experiment and SAED fringes calculation. The crystal was also confirmed with Rietveld refinement of XRD profile fitted with R-3c model Additionally, magnetic interaction with bacterial cell wall showed antimicrobial property against Escherichia coli, Gram-negative and Staphylococcus aureus, Gram-positive species. The approach transcribed in this paper reveals a novel methodology that utilizes α-Fe2O3 NPs to initiate apoptosis and inhibition of cervical cancer cells.

Novel photosensitizing properties of porphyrin–chrysin derivatives with antitumor activity in vitro

Photodynamic therapy is a promising cancer treatment with the advantages of low toxicity, high efficiency, and noninvasiveness. In this study, 23 novel porphyrin–chrysin derivatives are synthesized using alkyl carbon chains as bridges. We use human gastric cancer cells (MGC-803) and human cervical cancer cells to evaluate the in vitro antitumor activity of all the porphyrin–chrysin derivatives, with 5-fluorouracil (5-Fu) as a positive control. Several of the prepared compounds showed effective photodynamic killing effects, among which 5-hydroxy-2-phenyl-7-(2-(4-(10,15,20-tris(4-hydroxyphenyl)porphyrin-5-yl)phenoxy)ethoxy)-4 H-chromen-4-one shows the highest antiproliferation activity on human cervical cancer cells, with a half maximal inhibitory concentration of 26.51 ± 1.15 µM. Flow cytometry analysis showed that human cervical cancer cell apoptosis might be induced by G1 phase arrest.

MicroRNA‑126‑3p suppresses HeLa cell proliferation, migration and invasion, and increases apoptosis via the PI3K/PDK1/AKT pathway

We previously reported that relative to normal cervical mucus, microRNA 126-3p (miR-126-3p) is present in significantly greater amounts in the cervical mucus of patients with overt cervical cancer or precursor lesions. Here, we investigated the effects of enforced miR-126-3p expression in the cervical cancer cell line, HeLa, on proliferation, migration, invasion, apoptosis and protein expression. We transfected HeLa cells with miR-126-3p miRNA and found that proliferation, migration and invasion by cell counting, wound healing, cell migration and invasion assay were significantly reduced in these cells relative to those transfected with a negative control mimic. The levels of phosphoinositide 3 kinase (PI3K), phosphorylated 3-phosphoinositide-dependent protein kinase-1 (p-PDK1) and p-AKT proteins were lower in the miR-126-3p-transfected cells. Phosphorylated 70S6K (p-p70S6K), phosphorylated glycogen synthase kinase 3β (p-GSK3β), phosphorylated S6K (p-S6K), cyclin D1, phosphorylated p21-activated kinase 1 (p-PAK1), Rho associated coiled-coil containing protein kinase 1 (ROCK1), myotonic dystrophy-related CDC42-binding kinases α (MRCKα) and phospholipase C γ1 (p-PLCγ1) were also downregulated. This suggests that downstream effectors of the PI3K/PDK1/AKT pathway are targets for inhibition by miR-126-3p. In contrast, apoptotic-related proteins including the BCL-2-associated agonist of cell death (Bad), B-cell lymphoma-extra-large (Bcl-xL) and BCL-2-associated X (Bax), were all upregulated by miR-126-3p, resulting in increased caspase 3/7 activity and apoptosis. Thus, enforced expression of miR-126-3p inhibited cell migration and invasion and also induced apoptosis by regulating the PI3K/PDK1/AKT pathway in HeLa cells. Hence, high levels of miR-126-3p may inhibit cervical carcinogenesis, and targeting the PI3K/PDK1/AKT pathway via miR-126-3p could represent a new approach for treating patients with cervical cancer.