• BMB Reports
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• v.47 no.8
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• pp.433-438
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• 2014

Plant sterols have shown potent anti-proliferative effects and apoptosis induction against breast and prostate cancers. However, the effect of sterols against hepatic cancer has not been investigated. In the present study, we assessed whether the stigmasterol isolated from Navicula incerta possesses apoptosis inductive effect in hepatocarcimona (HepG2) cells. According to the results, Stigmasterol has up-regulated the expression of pro-apoptotic gene expressions (Bax, p53) while down-regulating the anti-apoptotic genes (Bcl-2). Probably via mitochondrial apoptosis signaling pathway. With the induction of apoptosis caspase-8, 9 were activated. The DNA damage and increase in apoptotic cell numbers were observed through Hoechst staining, annexin V staining and cell cycle analysis. According to these results, we can suggest that the stigmasterol shows potent apoptosis inductive effects and has the potential to be tested as an anti-cancer therapeutic against liver cancer.

• The Journal of Korean Medicine
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• v.21 no.4
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• pp.183-192
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• 2000

Objectives : The present study was carried out to investigate the effects of Danchun-hwan(DCH) on the peroxynitrite-induced neural cell death in human neuroblastoma cell line, SH-SY5Y. Methods : The cultured cells were pretreated with DCH and exposed to 3-morpholinosydnonimine(SIN-1) that simultaneously generates NO and superoxide, thus possibly forming peroxynitrite. The cell damage was assessed by using MTT assay and crystal violet staining. Results : Exposure of the cells to SIN-1 for 24hr induced 75% apoptotic cell death, as evaluated by the occurrence of morphological nuclear changes characteristic of apoptosis using 4', 6-diamidino-2-phenylinole(DAPI). However, pretreatment of SH-SY5Y with the water extracts of DCH, inhibited the apoptotic cell death in a dose-dependent manner. DCH also inhibited SIN-1-induced apoptotic caspase 3-like protease activity in a dose-dependent manner. DCH recovered the depleted glutathione levels by SIN-1. Conclusions : Taken together, it is suggested that DCH protected human neuroblastoma cell line, SH-SY5Y, from the free radical injury mediated by peroxynitrite by a mechanism of elevating antioxidant, GSH.

• Journal of Microbiology and Biotechnology
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• v.21 no.5
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• pp.525-528
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• 2011

The Raf-1 kinase inhibitory protein (RKIP) can regulate multiple key signaling pathways. Specifically, RKIP binds to Raf-1 kinase and inhibits the Ras-Raf-1-MEK1/2- ERK1/2 pathway. Additionally, Raf-1 has been shown to translocate to mitochondria and thereby protect cells from stress-mediated apoptosis. Recently, HBx was found to stimulate the mitochondrial translocation of Raf-1, contributing to the anti-apoptotic effect. We found that RKIP was downregulated during HBx-mediated hepatocarcinogenesis. In this study, we show that RKIP bound to Raf-1 and consequently inhibited the translocation of Raf-1 into mitochondria. This promoted the apoptosis of cells treated with apoptotic stimulus. Thus, the downregulation of RKIP increased the level of free Raf-1 and thereby elevated the mitochondrial translocation of Raf-1 during HBx-mediated hepatocarcinogenesis. The elevated Raf-1 mitochondrial translocation induced the increased anti-apoptotic effect and subsequently promoted HBx-mediated hepatocarcinogenesis.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1511-1514
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• 2012

Objective: The present study aimed to investigate the influence of siRNA interference with a proliferation-inducing ligand (APRIL) gene on gastric carcinoma sgr-7901 cell apoptosis. Correlations between APRIL silencing and tyrosine kinase (trka) expression were also explored. Methods: Two APRIL-silencing siRNA vectors were constructed, and transfected into human gastric carcinoma sgr-7901 cells, expression before and after transfection being detected using RT-PCR and western blot analyses. The expression of 15 trka genes was detected using RT-PCR and apoptotic rates of sgr-7901 were assessed by flow cytometry. Results: The expression levels of receptor trka genes were significantly decreased, and the apoptotic rate of sgr-7901 was significantly increased after transfection (P < 0.05). Conclusion: APRIL gene silencing can increase the apoptotic rate of gastric carcinoma cells, and inhibit the expression of receptor trka genes. There is a correlation between the signaling pathways of APRIL and trka.

• YAKHAK HOEJI
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• v.56 no.3
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• pp.173-179
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• 2012

Saussurea lappa (SL) and major compounds, sesquiterpene lactones, have been suggested to possess various biological effects, including anti-tumor, anti-ulcer, anti-inflammatory, anti-viral and cardiotonic activities. Therefore, the ethanol extract of Saussurea lappa root (ESL) is studied for the mechanism of its action in apoptotic pathway. ESL-treated cells manifested nuclear condensation, and fragmentation. ESL also triggered the mitochondrial apoptotic pathway, as indicated by a change in Bax/Bcl2 ratio and caspase-9/-3 activation. ESL induced p38 MAPK/JNK, p53, and ASK1 phosphorylation. ROS scavenger reversed ESL-induced apoptotic cell death via inhibition of caspase-3 and p38 MAPK/JNK phosphorylation. These results suggest that ESL induced apoptosis in HepG2 cells through the ROS-p38/JNK pathway.

• Korean Journal of Veterinary Research
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• v.39 no.6
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• pp.1112-1118
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• 1999

Galectin-3 plays an important role in cell development, differentiation and cancer metastasis, including cell-cell/extracellular matrix (ECM) interactions and is supposed to have an effect of apoptosis on T-cells in thymic clonal selection. In this study, to know the effect of galectin-3 on thymocyte development, we used recombinant human galectin-3 (rHgal-3) from Escherichia coli, JM105, which was inserted with human gal-3 gene-transformed plasmid vector (prGal-3) to express human galectin-3. Expressed rHgal-3 was confirmed by western blot using the culture supernant of hybridoma (M3/38) producing monoclonal antibody to human galectin-3. Sepharose gel affinity chromatography was used to purify the expressed rHgal-3. Thymocytes and hepatocytes from 6-week-old male BALB/c mice were incubated with rHgal-3 and showed marked increase of apoptotic population on analysis using flow cytometry with 7-AAD in a dosedependent manner. However, rHgal-3 failed to induce apoptosis on hepatocytes. Interestingly, this apoptotic effect was not inhibited by lactose, a specific lectin domain inhibitor. From these results, we concluded that extrinsic -3 induces apoptosis on mouse thymocytes, and galectin-3 may have an apoptotic effect on T-cells in thymic clonal selection.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.6
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• pp.1423-1430
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• 2009

Rosmarinic acid frequently found as a secondary metabolite in herbs and medicinal plants, has exhibited antimicrobial, antiviral, antioxidative, and anti-inflammatory activities. The proliferation and migration of human aortic smooth muscle cells (HASMC) in response to activation by various stimuli plays a critical role in the initiation and development of atherosclerosis. This study was conducted to examine the effects of Rosmarinic acid on the proliferation and migration of HASMC. Rosmarinic acid suppressed the proliferation of HASMC via induction of the expression of apoptotic proteins including cleaved poly ADP-ribose polymerase (PARP), and caspase-3. Rosmarinic acid decreased anti-apoptotic Bcl-2 and increased pro-apoptotic Bax. Moreover, treatment of rosmarinic acid decreased the G1/S cycle regulation proteins (cyclin D1, cyclin E, CDK2, CDK4 and CDK6) and increased p21, p27 and p53. Rosmarinic acid also blocked HASMC migration via suppression of MMP-9 and MMP-2. Taken together, these results indicate that rosmarinic acid has the potential for use as an anti-atherosclerosis agent.

• Journal of Life Science
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• v.29 no.11
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• pp.1227-1234
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• 2019

Prunus mume, also known as maesil, is a popular fruit consumed in East Asia (Korea, Japan, and China). It contains high amounts of organic acids, minerals, and polyphenols and has been used as a medication for fever, vomiting, and detoxification. In this study, the anti-proliferative and apoptotic effects of solvent fractions from maesil were evaluated using sulforhodamine B (SRB) assays, morphological evaluations, Hoechst 33258 staining, and western blotting. Addition of the maesil methanol fraction (MMF) and the maesil butanol fraction (MBF) significantly and dose-dependently decreased the cell viability of HT-29 human colon cancer cells. Colony-forming assays confirmed that the MMF and MBF treatments decreased colony numbers when compared with untreated control cells. Treatment of HT-29 cells with MMF and MBF caused a distortion of the cell morphology to a shrunken cell mass. Treatment with MMF and MBF also dose-dependently increased nuclear condensation and the formation of apoptotic bodies in HT-29 cells. Treatment with MMF and MBF significantly and dosedependently increased the expression of Bax (a pro-apoptotic protein), caspase-3, and poly ADP-ribose polymerase (PARP) and decreased the expression of Bcl-2 (an anti-apoptotic protein). MMF significantly and dose-dependently inhibited cell proliferation induced by bisphenol A, an environmental hormone. Therefore, MMF may have potential use as a functional food and as a possible therapeutic agent for the prevention of colon cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3363-3368
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• 2014

Background: Curcumin, a phenolic compound extracted from the rhizomes of Curcuma longa, has shown cytotoxic effects against a variety of cancers. The aim of this study was to identify potential microRNA (miRNA) mediators of the anticancer effects of curcumin in ovarian cancer cells. Materials and Methods: SKOV3 ovarian cancer cells were treated with curcumin ($10-60{\mu}M$) and miR-9 expression, cell proliferation, and apoptosis were assessed. The effects of miR-9 depletion on curcumin-mediated growth suppression were also examined. Phosphorylation of Akt and forkhead box protein O1 (FOXO1) was measured in cells with miR-9 overexpression or curcumin treatment. Results: Curcumin caused a significant and dose-dependent increase of miR-9 expression in SKOV3 cells, while significantly impeding cell proliferation and stimulating apoptosis. Depletion of miR-9 significantly (p<0.05) attenuated the growth-suppressive effects of curcumin on SKOV3 cells, coupled with reduced percentages of apoptotic cells. In contrast, overexpression of miR-9 significantly enhanced the cleavage of caspase-3 and poly(ADP-ribose) polymerase and promoted apoptotic death in SKOV3 cells. Western blot analysis showed that both miR-9 overexpression and curcumin similarly caused a significant (p<0.05) decline in the phosphorylation of Akt and FOXO1, compared to untreated cells. Conclusions: The present study provided evidence that curcumin exerts its cytotoxic effects against SKOV3 ovarian cancer cells largely through upregulation of miR-9 and subsequent modulation of Akt/FOXO1 axis. Further studies are needed to identify direct targets of miR-9 that mediate the anticancer effects of curcumin in ovarian cancer cells.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3281-3287
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• 2016

Bioactive compounds extracted from leaves and twigs of Goniothalamus griffithii include pinocembrin (PCN) and goniothalamin (GTN). The objectives of this study were to investigate the cytotoxic activities of PCN and GTN and their influence on molecular signaling for cell death in several human cancer cell lines compared to normal murine fibroblast NIH3T3 cells. GTN exhibited the most potent cytotoxicity against MCF-7 > HeLa > HepG2 > NIH3T3 cells with $IC_{50}$ values of 7.33, 14.8, 37.1 and $65.4{\mu}M$, respectively, whereas PCN was cytotoxic only to HepG2 cells with $IC_{50}$ values of ${\sim}80{\mu}M$. Apoptotic cell death was confirmed by staining the cells with annexin V-FITC and propidium iodide (PI) employing flow cytometry. Apoptosis was shown by externalization of phosphatidylserine in goniothalamin-treated MCF-7 cells in a dose response manner. Positive PI-stained cells with the typical morphology of apoptotic cells were increased dose-dependently. Furthermore, reduction of mitochondrial transmembrane potential was found in goniothalamin-treated MCF-7, HepG2 and HeLa cells. GTN treatment in MCF-7 increased caspase-3, -8 and -9 activities while GTN-induced HeLa cells showed an increase of both caspase-3 and -9 activities. But an increased caspase-8 activity was demonstrated in GTN- and PCN-treated MCF-7 and HepG2 cells, respectively. Taken together, GTN- and PCN-induced human cancer cell apoptosis was through different molecular mechanisms or signaling pathways, which might be due to different machineries in different types of cancer cells, as evidenced by the compound-modulated caspase activities in both intrinsic and/or extrinsic pathways.