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Acyclovir induces cell cycle perturbation and apoptosis in Jurkat leukemia cells, and enhances chemotherapeutic drug cytotoxicity.

AIMS AND METHODS: Many antiviral agents have been reported to present direct cytotoxic activity in cancer, showing antiproliferative and proapoptotic effects through different mechanisms. In the present study, we took into account the cytotoxic action of the antiviral drug acyclovir (ACV) on leukemia cells, by investigating cell cycle perturbations and apoptosis induction upon drug administration to three still unexplored cell lines, namely Jurkat, U937, and K562. At the same time, the cytotoxicity of cisplatin (CDDP) and 5‑fluorouracil (5‑FU) in combination with ACV was assessed, thus to eval

δ-Catenin promotes tumorigenesis and metastasis of lung adenocarcinoma.

δ-Catenin coded by gene CTNND2 has been found to be overexpressed in various types of cancers, including prostate, breast, lung and ovarian cancers. However, the function of δ-catenin in lung carcinoma remains largely unknown. In the present study, we revealed that δ-catenin acts as an oncogene promoting the malignancy of lung adenocarcinoma. When δ-catenin proteins of Lewis lung cells were depleted by knocking out Ctnnd2 via CRISPR/Cas9 technology, the cells lost the tumorigenic and metastatic abilities in vivo. Consistently, overexpression of Ctnnd2 enhances the subcutaneous tumorigenesis an

FNC efficiently inhibits mantle cell lymphoma growth.

FNC, 2'-deoxy-2'-β-fluoro-4'-azidocytidine, is a novel cytidine analogue, that has shown strong antiproliferative activity in human lymphoma, lung adenocarcinoma and acute myeloid leukemia. In this study, we investigated the effects of FNC on mantle cell lymphoma (MCL) and the underlying mechanisms. In in vitro experiments, cell viability was detected by the CCK8 assay, and cell cycle progression and apoptosis were assessed by flow cytometry, and the expression of relative apoptosis proteins were detected by Western Blot. The in vivo antitumor effect of FNC was investigated in a SCID xenograft

Carvacrol Induces Reactive Oxygen Species (ROS)-mediated Apoptosis Along with Cell Cycle Arrest at G0/G1 in Human Prostate Cancer Cells.

Carvacrol, a major monoterpenoid phenol from Origanum and Thymus species, has been shown to exhibit antiproliferative and anticancer propert … osis of prostate cancer cells was also accompanied by significant amount of growth arrest at the G0/G1 phase of the cell cycle which has also not been documented previously. To sum up, this study has established that carvacrol could be a promising chemotherapeutic agent and could have a direct practical implication and translational relevance to prostate c …

HDAC inhibition as a treatment concept to combat temsirolimus-resistant bladder cancer cells.

INTRODUCTION: Although the mechanistic target of rapamycin (mTOR) might be a promising molecular target to treat advanced bladder cancer, resistance develops under chronic exposure to an mTOR inhibitor (everolimus, temsirolimus). Based on earlier studies, we proposed that histone deacetylase (HDAC) blockade might circumvent resistance and investigated whether HDAC inhibition has an impact on growth of bladder cancer cells with acquired resistance towards temsirolimus. RESULTS: The HDAC inhibitor valproic acid (VPA) significantly inhibited growth, proliferation and caused G0/G1 phase arrest in…

Overexpression of TSPAN8 Promotes Tumor Cell Viability and Proliferation in Nonsmall Cell Lung Cancer.

BACKGROUND: Overexpression of TSPAN8 has been involved in several epithelial cancers and TSPAN8 can form a complex with a variety of protein … in 95C dramatically enhanced cell viability and proliferation. In addition, TSPAN8 knockdown led to G1 phase arrest and apoptosis by downregulating CDK2, CDK4, and Cyclin D1 and upregulating Bax and PARP. CONCLUSIONS: These results provide evidence that TSPAN8 may contribute to the pathogenesis of lung cancer by promoting cell viability and proliferation. …

HMGA2 is associated with the aggressiveness of tongue squamous cell carcinoma.

OBJECTIVE: To analyze the effects of HMGA2 on proliferation, invasion, and metastasis in tongue squamous cell carcinoma (TSCC). METHODS: HMGA2 knockdown was performed in SCC15 cell lines, and functional assay was applied to observe the effects on cell migration and invasion. Real-time PCR, Western blotting, and immunohistochemistry (IHC) were also used to measure the expression of HMGA2 and EMT markers. RESULTS: HMGA2 expression was decreased after lentivirus infection. Functional assay showed that silence of HMGA2 can inhibit the proliferation of SCC15 cells and arrest the cells in G1/S pha

Roseotoxin B Improves Allergic Contact Dermatitis through a Unique Anti-Inflammatory Mechanism Involving Excessive Activation of Autophagy in Activated T Lymphocytes.

An immunosuppressant agent with negligible or acceptable toxicity may provide a better therapeutic strategy for treatment of allergic contact dermatitis. We identified a natural cyclopeptide, roseotoxin B, that effectively suppressed cell proliferation and the production of proinflammatory cytokines in activated T cells but exhibited little naive T-cell toxicity at concentrations of 0.3-1 μmol/L. In addition, roseotoxin B inhibited the activation of AKT and signal transducer and activator of transcription-3, suppressed cell cycle-related signaling, caused G0/G1 phase arrest, reduced ribosomal …

Deubiquitinase USP9X deubiquitinates β-catenin and promotes high grade glioma cell growth.

β-catenin is a crucial signal transduction molecule in the Wnt/β-catenin signal pathway, and increased β-catenin expression has consistently been found in high grade gliomas. However, the mechanisms responsible for β-catenin overexpression have remained elusive.Here we show that the deubiquitinase USP9X stabilizes β-catenin and thereby promotes high grade glioma cell growth. USP9X binds β-catenin and removes the Lys 48-linked polyubiquitin chains that normally mark β-catenin for proteasomal degradation. Increased USP9X expression correlates with increased β-catenin protein in high grade glioma

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… Compared with the control group and si-NC group, the G1 phase of the siRNA 1-3 groups was significantly longer ( P <0.05) ( Supplementary Figure S2a, S2b ). In contrast, the duration of the S phase of the siRNA 1-3 groups decreased ( P <0.05) ( Supplementary Figure S2 c,d). …

Bafilomycin A1 induces caspase-independent cell death in hepatocellular carcinoma cells via targeting of autophagy and MAPK pathways.

Hepatocellular carcinoma (HCC) is refractory to chemotherapies, necessitating novel effective agents. The lysosome inhibitor Bafilomycin A1 (BafA1) at high concentrations displays cytotoxicity in a variety of cancers. Here we show that BafA1 at nanomolar concentrations suppresses HCC cell growth in both 2 dimensional (2D) and 3D cultures. BafA1 induced cell cycle arrest in the G1 phase and triggered Cyclin D1 turnover in HCC cells in a dual-specificity tyrosine phosphorylation-regulated kinase 1B (DYRK1B) dependent manner. Notably, BafA1 induced caspase-independent cell death in HCC cells by i…

Dose-dependent and cell type-specific cell death and proliferation following in vitro exposure to radial extracorporeal shock waves.

Radial extracorporeal shock wave (rESW) therapy is widely used in musculoskeletal disorders and wound repair. However, the mechanisms of action are still largely unknown. The current study compared the effects of rESWs on two cell types. Human fetal foreskin fibroblasts (HFFF2) and human placental choriocarcinoma cell line JEG-3 were exposed to 0, 100, 200, 500 or 5000 rESWs generated with a Swiss DolorClast device (2.5 bar, 1 Hz). FACS analysis immediately after rESW exposure showed that initially, rESWs rather induced mechanical cell destruction than regulated or programmed cell death. Cell

Loss of MiR-664 Expression Enhances Cutaneous Malignant Melanoma Proliferation by Upregulating PLP2.

Proteolipid protein 2 (PLP2) has been shown to be upregulated in several cancers, including breast cancer, hepatocellular carcinoma, osteosarcoma, and melanoma. PLP2 specifically binds to phosphatidylinositol 3 kinase to activate the protein kinase B pathway to enhance cell proliferation, adhesion, and invasion in melanoma cells. Therefore, we speculated that PLP2 exhibits oncogenic potential. However, the regulatory mechanisms of PLP2 in cancer cells remain unclear.Herein, we found that microRNA (miR)-664 expression was significantly downregulated in cutaneous malignant melanoma (CMM) cells a

Upregulation of KPNβ1 in gastric cancer cell promotes tumor cell proliferation and predicts poor prognosis.

KPNβ1, also known as importin β, P97, is reported as one of soluble transport factors that mediates transportion of proteins and RNAs betwee … cancer cells, while KPNβ1 knockdown led to decreased cell proliferation and arrested cell cycle at G1 phase. Furthermore, our results also indicated that KPNβ1 expression could result in docetaxel resistance. And, KPNβ1 could interact with Stat1, contributed to its nucleus import in gastric cancer cells. These findings provided a novel promising therapeut …

Combination of metformin and valproic acid synergistically induces cell cycle arrest and apoptosis in clear cell renal cell carcinoma.

OBJECTIVE: To investigate the antitumor activity of metformin combined with valproic acid (VPA) on renal cell carcinoma (RCC) cell lines. M … <0.05). Furthermore, metformin and VPA acted synergistically to arrest 786-O and Caki-2 cells in G0/G1 phase. CONCLUSION: We highlighted for the first time that metformin combined with VPA could significantly increase anti-ccRCC effect through synergetic effect; its possible mechanisms were inducing apoptosis and adjusting cell cycle.

Cannabinoid receptor CB1 regulates STAT3 activity and its expression dictates the responsiveness to SR141716 treatment in human glioma patients' cells.

Herein we show that a majority of human brain tumor samples and cell lines over-expressed cannabinoid receptor CB1 as compared to normal human astrocytes (NHA), while uniformly expressed low levels of CB2. This finding prompted us to investigate the therapeutic exploitation of CB1 inactivation by SR141716 treatment, with regard to its direct and indirect cell-mediated effects against gliomas. Functional studies, using U251MG glioma cells and primary tumor cell lines derived from glioma patients expressing different levels of CB1, highlighted SR141716 efficacy in inducing apoptosis via G1 phase…

Tetrandrine Inhibits the Intracellular Calcium Ion Level and Upregulates the Expression of Brg1 and AHNAK in Hep-2 Cells.

BACKGROUND: Tetrandrine has been found to inhibit the growth of various types of tumor cells, but the underlying molecular mechanism remains … -2 cells as indicated by an IC50 value of 13.28 μg/mL. Tetrandrine induced cell cycle arrest at the G1 phase and decreased the intracellular concentration of Ca2+ in a concentration dependent manner. Intriguingly, tetrandrine upregulated Brg1 expression in a dose-and time-dependent pattern and elevated the expression of AHNAK in Hep-2 cells. CONCLUSIONS: …

Fighting against human papillomavirus: the 25-year old contribution of the University of Crete School of Medicine.

Twenty five years have passed since the first research efforts in Greece on human papillomavirus (HPV) performed by the Department of Clinical Virology at the University of Crete School of Medicine. HPV infection in the human cervix was initially evaluated in relation to the host mutational and transcriptional activation of the ras/raf genes pathway, p53 gene polymorphisms, neo-angiogenesis- related gene expression and G1/S phase transition. A series of epidemiological studies ensued, evaluating HPV infection in the ophthalmic pterygium, benign laryngeal tumors, parotid lesions, nasal polyposi

Effects of quercetin on hedgehog signaling in chronic myeloid leukemia KBM7 cells.

OBJECTIVE: To investigate the effects of quercetin on Hedgehog (Hh) signaling in chronic myeloid leukemia KBM7 cells. METHODS: The KBM7 cel … significantly inhibited KBM7 cell proliferation, induced cell apoptosis, and blocked cell cycle at G1 phase, which were in dose-dependent manners. The mRNA and protein expression of Smoothened and Glioma1 (Gli1), the members of Hh pathway decreased after treatment with quercetin. The Bcl-2 and Cyclin D1, targets of Hh signaling, also decreased after treat …

Enhanced autophagy by everolimus contributes to the antirestenotic mechanisms in vascular smooth muscle cells.

OBJECTIVE: The present study aims to investigate the underlying mechanisms accounting for the activities of everolimus to inhibit the growth … downregulating proliferating cellular nuclear antigen. Everolimus induced cell cycle arrest at the G1 phase by downregulating cyclin D1 and upregulating p27, and increased apoptosis by downregulating Bcl-2, upregulating Bad and activating capsase-3 and poly ADP ribose polymerase. Everolimus enhanced autophagy by increasing the conversion of microtubule-as …

Src kinase function controls progenitor cell pools during regeneration and tumor onset in the Drosophila intestine.

Src non-receptor kinases have been implicated in events late in tumor progression. Here, we study the role of Src kinases in the Drosophila intestinal stem cell (ISC) lineage, during tissue homeostasis and tumor onset. The adult Drosophila intestine contains only two progenitor cell types, division-capable ISCs and their daughters, postmitotic enteroblasts (EBs). We found that Drosophila Src42a and Src64b were required for optimal regenerative ISC division. Conversely, activation of Src42a, Src64b or another non-receptor kinase, Ack, promoted division of quiescent ISCs by coordinately stimulat