• Journal of Life Science
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• v.27 no.7
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• pp.834-839
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• 2017

Propolis is a natural product collected from plants by honey bees product used extensively in traditional medicine for its antioxidant, anti-inflammatory, immunomodulatory and anti-cancer effects. Propolis exhibits a broad spectrum of biological activities because it is a complex mixture of natural substances. Ovarian cancer is the second most common newly diagnosed cancer from all cancers among women in Korea and the leading cause of death from gynecological malignancies. While most ovarian cancer patients initially respond to surgical debulking and chemotherapy, patients later succumb to the disease. Thus, there is an urgent need to test novel therapeutic agents to counteract the high mortality rate associated with ovarian cancer. In this study, we investigated the anti-cancer properties and the active mechanism of Australian propolis in human epithelial ovarian cancer A2780 cells. Our data revealed that propolis showed a cytotoxic activity in a dose-dependent manner. Flow cytometric analysis for cell cycle arrest and apoptosis using propidium iodide staning and annexin V-FITC indicated that propolis could induce cycle arrest in the G0/G1 phase and apoptosis in a dose-dependent manner on human epithelial ovarian cancer cells. These results suggest that the Australian propolis is potential alternative agent on ovarian cancer prevention and treatment.

• Journal of Life Science
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• v.17 no.1 s.81
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• pp.64-69
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• 2007

In the present study, we have investigated the effect of fisetin on the apoptosis and DNA single strand breaks in ultraviolet light B (UVB)-exposed NIH3T3 cells. Exposure of cells to UVB light $(200J/m^2)$ and post-incubation in growth medium for 48 hr resulted in about 50% of cells with apoptotic nuclear fragmentation. Addition of various concentrations of fisetin in the postincubation medium, however, significantly reduced the apoptotic nuclear fragmentation as compared with the values expected when the effects are additive and independent. DNA single strand breaks induced by UVB exposure were also significantly decreased by postincubation with fisetin. By Western blot analysis, fisetin post-incubation was shown to attenuate the p53 upregulation upon UVB exposure. Furthermore, the decrease of proliferating cell nuclear antigen (PCNA) level upon UVB exposure was alleviated by fisetin postincubation. These results suggest that fisetin decrease the apoptosis and increae DNA repair in a possible association with alteration of p53 and PCNA levels in UVB-exposed cells.

• Journal of Life Science
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• v.25 no.3
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• pp.336-344
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• 2015

The capacity for liver regeneration involves a variety of nutritional factors. Vitamin C has multiple metabolic and antioxidant functions. In this study, we investigated the role of vitamin C in liver regeneration following hepatectomy in senescence marker protein (SMP)-30 knockout (KO) mice. Partial hepatectomy was performed by resecting the median and left lateral lobes of mice. Vitamin C accelerated liver recovery in SMP30 KO mice treated with vitamin C (KV). The livers of the KV mice exhibited lower levels of aspartate aminotransferase and lower injury than those of the KO mice. Increased type II transforming growth factor-β receptor (TGF-βRII)-mediated regeneration signaling was accompanied by HGF and cMet in the KV but not the KO mice. Consistent with this, the expression of cell cycle regulatory proteins, including cyclin D1 and proliferating cell nuclear antigen (PCNA), increased rapidly in the KV mice. Enhanced activation of ERK and GSK-3β proteins and a significantly increased number of binuclear hepatocytes were also detected in the livers of the KV mice. Moreover, the KV mice synthesized the highest levels of albumin. These data suggest that treating SMP30 knockout mice with vitamin C resulted in earlier recovery and liver regeneration by activation of the regeneration system.

• Journal of Life Science
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• v.17 no.7 s.87
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• pp.896-904
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• 2007

Regulation mechanism of apoptosis has been known to be important for understanding the pathogenesis of a number of human diseases including cancers. The effects of $RRR-{\alpha}-tocopheryl$ succinate(vitamin E succinate, VES) on the cell viability, generation of ROS, expression of proteins involved in apoptosis, and growth of human chronic myelogenous leukemia K562 cells were analyzed in this study. VES treatment not only induced the generation of the ROS but also increased the levels of $NF-{\kappa}B$, COX-2, and $p21^{WAF1/CIP1}$ in K562 cells. It modulates the levels of pro-apoptotic proteins such as Bax provoking the apoptosis in K562 cells. The cleavage of PARP into 89 kDa was also increased upon VES treatment in a dosage-dependent manner. Induction of an apoptosis was evident by the increase of sub-Gl peak and cell shrinkage condensed chromatin in K562 cells treated with VES. It also resulted in an inhibition of tumor growth by 50% and prolonged survival of the Iymphoma-induced mice. This potentiation of VES obtained in vitro and in vivo may indicate the feasibility of more effective chemotherapy in chronic myelogenous leukemia.

• Journal of Life Science
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• v.17 no.7 s.87
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• pp.1019-1022
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• 2007

Thrombolytic therapy with tissue plasminogen activator (tPA) can improve the clinical outcome of ischemic stroke patients. However, its clinical application is limited by narrow therapeutic time windows and elevated risks of cerebral hemorrhage and brain injury. In part, these effects of tPA has been related to matrix metalloproteinase-9 (MMP-9) dysregulation. Here, we investigate that the effects of alteplase (tPA with short half-life) and pamiteplase (a modified tPA with long half-life) on the MMP-9 regulation in neurovascualr unit. The total levels of MMP-2 and MMP-9 in neuronal cells are lower than astrocytes. Alteplase (1-10 ${\mu}g/ml$) induced upregulation of MMP-2 and MMP-9 in rat cortical neurons and astrocytes, respectively. Whereas pamiteplase in a wide range of dose did not affect the MMP-2 and MMP-9 responses in both of cells. These results suggest that pamiteplase with long half-life can be provided as a agent that overcome the side effects of alteplase.

• Journal of Life Science
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• v.19 no.8
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• pp.1047-1054
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• 2009

Oral squamous carcinoma (OSC) cells present resistance to chemotherapeutic agents-mediated apoptosis in the late stages of malignancy. Advances in the understanding of bacterial toxins have produced new strategies for the treatment of cancers. It was demonstrated here that Pseudomonas aeruginosa exotoxin A (PEA) significantly decreased the viability of chemoresistant YD-9 cells in the apoptosis mechanism. Apoptotic manifestations were evident through changes in nuclear morphology and generation of DNA fragmentation. PEA treatment induced caspase-3, -6 and -9 cleavage, and activation. These events preceded proteolysis of the caspase substrates poly (ADP-ribose) polymerase (PARP), DNA fragmentation factor 45 (DFF45), and lamin A in YD-9 cells. The reduction of mitochondrial membrane potential, release of cytochrome c and SmacjDlABLO from mitochondria to cytosol, andtranslocation of AlF into nucleus were shown. While p53, p21 and $14-3-3{\gamma}$ were upregulated, cyclin Band cdc2 were downregulated by PEA treatment. Taken together, PEA induces apoptosis in chemoresistant YD-9 cells via activation of caspases, mitochondrial events and regulation of cell cycle genes.

• Journal of Life Science
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• v.26 no.9
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• pp.1015-1021
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• 2016

5-fluorouracil (5-FU), a pyrimidine analog, is a widely used anticancer drug, which works through irreversible inhibition of thymidylate synthase. In the present study, it was investigated the anti-proliferative effects and molecular mechanisms of 5-FU using Ewing's Sarcoma CHP-100 Cells. The present data indicated that treatment of 5-FU to CHP-100 cells induced a G1 phase arrest of the cell cycle in a time-dependent manner. 5-FU-induced G1 arrest was correlated with the accumulation of the hypophosphorylated form of the retinoblastoma protein (pRB) and association of pRB with the transcription factors E2F-1 and E2F-4. Although 5-FU treatment did affect the levels of cyclin-dependent kinases, the levels of cyclin A and B were markedly down-regulated as compared with the untreated control group. In addition, 5-FU-induced G1 arrest of CHP-100 cells was also associated with the induction of apoptosis, as determined by apoptotic cell morphologies, degradation of poly(ADP-ribose) polymerase and Annexin V staining. Furthermore, 5-FU induced the loss of mitochondrial membrane potential with up-regulated pro-apoptotic Bax expression, down-regulated anti-apoptotic Bcl-2 expression and cytochrome c release from mitochondria to cytosol. Collectively, the data suggest that 5-FU is effective in inducing cell growth reduction and apoptosis, in part, by reducing phosphorylation of pRB and activating mitochondrial dysfunction in CHP-100 cells.

• Microbiology and Biotechnology Letters
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• v.38 no.4
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• pp.442-447
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• 2010

We investigated anti-cancer and anti-proliferative activity of allicin and analyzed global gene expression changes by allicin treatment in human colorectal HCT116 cells. As a result, allicin decreased cell viabilities in a dose and time-dependent manner and induced apoptosis. Oligo DNA microarray analysis, we found that 7,840 genes were up-regulated more than 2-folds, whereas 10,010 genes were down-regulated more than 2-folds by $50\;{\mu}M$ allicin treatment. To confirm specific gene expressions, we performed RT-PCR. Consistent with the results of DNA microarray analysis, allicin dramatically induced ATF3 and NAG1 gene expression. Interestingly, NAG-1 protein expression was dependent on p53 presence. Taken together, our present results increase the knowledge of the molecular mechanism of anti-cancer and anti-proliferative activity mediated by allciin in human colorectal cancer cell.

• Journal of Life Science
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• v.20 no.7
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• pp.1121-1126
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• 2010

The oxidative stress induced by reactive oxygen species (ROS) may play an important role in the pathogenesis of neurodegenerative diseases. In this study, we investigated the neuroprotective effects of methanolic extracts of Prunella Spica (PSE) against $H_2O_2$-induced oxidative stress in PC12 cells. The cells exposed to $H_2O_2$-induced oxidative stress were treated with various concentrations of PSE; this treatment resulted in the induction of a dose-dependent protective effect, which was evidenced by the results of MTT reduction assay, lactate dehydrogenase (LDH) release assay, morphological assay, and colony-formation assay. Interestingly, we also observed reduction of apoptotic bodies in the Hoechst staining and flow cytometric analysis. These data show that apoptosis was significantly suppressed in the PC12 cells that were exposed to $H_2O_2$-induced oxidative stress and treated with PSE. These results suggest that Prunella Spica could be a new potential protective agent against $H_2O_2$-induced oxidative stress.

• Journal of Plant Biotechnology
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• v.41 no.4
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• pp.194-200
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• 2014

Monodehydroascorbate reductase (MDHAR) is an important enzyme that plays a role in the detoxification of reactive oxygen species (ROS) by maintaining reduced pool of ascorbate through recycling the oxidized form of ascorbate. In this study, we isolated a PagMDHAR1 gene from Populus alba ${\times}$ P. glandulosa, and investigated its expression characteristics. The PagMDHAR1 cDNA encodes a putative 434 amino acids containing FAD- and NAD(P)H-binding domains. Southern blot analysis indicated that a single nuclear gene encodes this enzyme. Northern hybridization analysis revealed that PagMDHAR1 is highly expressed in both suspension cells and flower tissues, while its expression levels were enhanced by drought, salt, cold, wounding and ABA. Therefore, PagMDHAR1 might be expressed in response to abiotic stress through the ABA-mediated signaling pathway in this poplar species, suggesting that the PagMDHAR1 plays an important role in the defense mechanisms against oxidative stress.