• Journal of Life Science
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• v.18 no.3
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• pp.336-343
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• 2008

Histone deacetylases (HDACs) inhibitors have emerged as the accessory therapeutic agents for various human cancers, since they can block the activity of specific HDACs, restore the expression of some tumor suppressor genes and induce cell differentiation, cell cycle arrest and apoptosis in vitro and in vivo. In the present study, we investigated that the effect of trichostatin A (TSA), an HDAC inhibitor, on the cell growth and apoptosis, and its effect on the nuclear factor-kappaB $(NF-{\kappa}B)$ activity in 267B1 human prostate epithelial cells. Exposure of 267B1 cells to TSA resulted in growth inhibition and apoptosis induction in and dose-dependent manners as measured by fluorescence microscopy, agarose gel electrophoresis and flow cytometry analysis. TSA treatment inhibited the levels of IAP family members such as c-IAP-1 and c-IAP-2 and induced the proteolytic activation of caspase-3, -8 and -9, which were associated with concomitant degradation of poly (ADP-ribose)-polymerase, ${\beta}-catenin$ and laminin B proteins. The increase in apoptosis by TSA was connected with the translocation of $NF-{\kappa}B$ from cytosol to nucleus, increase of the DNA binding as well as promoter activity of $NF-{\kappa}B$, and degradation of cytosolic inhibitor of KappaB $(I{\kappa}B)-{\alpha}$ protein. We therefore concluded that TSA demonstrated anti-proliferative and apoptosis-inducing effects on 267B1 cells in vitro, and that the activation of caspases and $NF-{\kappa}B$ may play important roles in its mechanism of action. Although further studies are needed, these findings provided important insights into the possible molecular mechanisms of the anti-cancer activity of TSA.

• International Journal of Oral Biology
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• v.45 no.4
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• pp.169-178
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• 2020

L-ascorbic acid (L-AA; vitamin C) induces apoptosis in cancer cells. This study aimed to elucidate the molecular mechanisms of L-AA-induced apoptosis in human laryngeal epidermoid carcinoma Hep-2 cells. L-AA suppressed the viability of Hep-2 cells and induced apoptosis, as shown by the cleavage and condensation of nuclear chromatin and increased number of Annexin V-positive cells. L-AA decreased Bcl-2 protein expression but upregulated Bax protein levels. In addition, cytochrome c release from the mitochondria into the cytosol and activation of caspase-9, -8, and -3 were enhanced by L-AA treatment. Furthermore, apoptosis-inducing factor (AIF) and endonuclease G (EndoG) were translocated into the nucleus during apoptosis of L-AA-treated Hep-2 cells. L-AA effectively inhibited the constitutive nuclear factor-κB (NF-κB) activation and attenuated the nuclear expression of the p65 subunit of NF-κB. Interestingly, L-AA treatment of Hep-2 cells markedly activated Akt and mitogen-activated protein kinase (MAPK; extracellular signal-regulated kinase 1/2, p38, and c-Jun N-terminal kinase [JNK]) and and LY294002 (Akt inhibitor), SB203580 (p38 inhibitor) or SP600125 (a JNK inhibitor) decreased the levels of Annexin V-positive cells. These results suggested that L-AA induces the apoptosis of Hep-2 cells via the nuclear translocation of AIF and EndoG by modulating the Bcl-2 family and MAPK/Akt signaling pathways.

• Journal of the Korean Society of Food Science and Nutrition
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• v.38 no.10
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• pp.1317-1323
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• 2009

In the present study, we investigated the anti-proliferation activity of Citrus grandis Osbeck peel (CGP) in HL60 (human promyelocytic leukemia) cells. It was found that 80% ethanol extract of CGP could inhibit the cell growth in a dose-dependent manner ($250{\sim}1,000{\mu}g/mL$), which was associated with morphological changes and apoptotic cell death such as depolarized mitochondrial membrane, formation of apoptotic bodies and increased populations of apoptotic sub-G1 phase. The results indicate that CGP extract inhibits the growth of HL60 cancer cells by the induction of apoptosis, which may be mediated by its ability to change the Bcl family proteins and increase the activation of caspase-3 and PARP. Therefore, it is suggested that CGP has the potential to provide a remarkable natural defense against the proliferation of HL60 cells.

• Proceedings of the Korean Society of Life Science Conference
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• 2007.10a
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• pp.43.1-43.1
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• 2007

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• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.5
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• pp.1418-1425
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• 2004

The water extract of Chongmyung-tang has been traditionally used for treatment of memory-disorder in oriental medicine. This study was designed to investigate the protective mechanisms of Chongmyung-tang on β-amyloid or H₂O₂-induced cytotoxicity in Neuro 2A cells. The water extract of Chongmyung-tang significantly reduced both β-amyloid or H₂O₂-induced cell death and apoptotic characteristics through reduction of intracellular peroxide generation. Also, it inhibited the mitochondrial dysfunction including the disruption of mitochondria membrane permeability transition(MPT) and the modulation in expression of Bcl-2 family proteins in H₂O₂-treated H9c2 cells. Furthermore, pretreatment of quercetin inhibited the activation of caspase-3, in turn, degradation of ICAD/DFF45 were completely abolished in H₂O₂-treated cells. Taken together, that data suggest that the protective effects of the water extract of Chongmyung-tang against β-amyloid induced oxidative injuries may be achieved through modulation of mitochondrial dysfunction.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.4
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• pp.1050-1054
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• 2005

Recently, arsenic compounds were considered as novel agents for treatment of acute promyelocytic leukemia and malignant tumors. However, it showed severe toxicity effect on normal tissue at the same time. In this study, to investigate the possible molecular mechanism (s) of arsenic compounds as candidate of anti-cancer drugs, we compared the abilities of two arsenic compounds, tetraarsenic oxide $(AS_4O_6)$ and arsenic trioxide (diarsenic oxide, $As_2O_3$), to induce cell growth inhibition as well as apoptosis induction in A549 human non-small cell lung cancer cells. Both $As_4O_6\;and\;As_2O_3$ treatment declined the cell growth and viability of A549 cells in a concentration-dependent manner, which was associated with induction of G1 arrest of the cell cycle and apoptotic cell death. However, $As_4O_6$ induced growth inhibition and apoptosis in A549 cells at much lower concentrations than $As_2O_3.\;As_4O_6$ down-regulated the levels of anti-apoptotic Bcl-2 protein, however, the levels of Bax, a pro-apoptotic protein, were up-regulated in a dose-dependent manner. In conclusion, $As_4O_6$ might be a new arsenic compound which may induce apoptosis in A549 cells by modulation the Bcl-2 family and deserves further evaluation.

• Journal of Life Science
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• v.17 no.10
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• pp.1447-1451
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• 2007

Through the screening of marine natural compounds that inhibit cancer cell proliferation, we previously reported that pectenotoxin-2 (PTX-2) isolated from marine sponges exhibits selective cytotoxicity against several cell lines in p53-deficient tumor cells compared to those with functional p53. However, the molecular mechanisms of its anti-proliferative action on malignant cell growth are not completely known. To further explore the mechanisms of its anti-cancer activity and to test whether the status of p53 in liver cancer cells correlates with their chemo-sensitivities to PTX-2, we used two well-known hepatocarcinoma cell lines, p53-deficient Hep3B and p53-wild type HepG2. We have demonstrated that PTX-2 markedly inhibits Hep3B cell growth and induces apoptosis whereas HepG2 cells are much more resistant to PTX-2 suggesting that PTX-2 seems to act by p53-independent cytotoxic mechanism. The apoptosis induced by PTX-2 in Hep3B cells was associated with the modulation of DNA fragmentation factor (DFF) family proteins, up-regulation of pro-apoptotic Bcl-2 family members such as Bax and Bcl-xS and activation of caspases (caspase-3, -8 and -9). Blockade of the caspase-3 activity by caspase-3 inhibitor, z-DEVD-fmk, prevented the PTX-2-induced growth inhibition in Hep3B cells. Moreover, treatment with PTX-2 also induced phosphorylation of AKT and extracellular-signal regulating kinase (ERK), but not c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MARK). Specific inhibitors of PI3K inhibitor (LY294002) and ERK1/2 inhibitor (PD98059) significantly blocks PTX-2-induced-anti-proliferative effects, whereas a JNK inhibitor (SP600125) and a p38 MAPK inhibitor (SB203580) have no significant effects demonstrating that the pro-apoptotic effect of PTX-2 mediated through activation of AKT and ERK signal pathway in Hep3B cells.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.316.2-316.2
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• 2002

Manassantin B classified into dineolignans have been isolated from Saururus chinensis Manassantin B was found to induce apoptosis in human promyelocytic leukaemia HL -60 cells with characteristic apoptotic features like increase of nucleosomalladder. apoptotic body ormation. flipping of membrane phosphatidylserine. Manassantin B induced FAS and FAS ligand expression, and activated caspase 8 which cleaved bid to tbid in cytosol. The release of cytochrome c to sytosol was accompanied with decrease of bcl-2 protein and incresase of tbid and bax protein in mitochondria. Released xytochrome c activated caspase 9 and-3. but these effects were completely attenuated by the treatment of broad caspses ingibitor. Z-VAD fmk. These results indicate that manassatin B induce apoptosis through upregulation of FAS. caspase family and mitochondria-related proteins.

• Journal of Pharmacopuncture
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• v.25 no.3
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• pp.216-223
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• 2022

Objectives: Oxidative stress plays a key role in chronic and acute brain disorders and neuronal damage associated with Alzheimer disease (AD) and other neurodegeneration symptoms. The neuroprotective effects of berberine and Berberis vulgaris (barberry) root extract against apoptosis induced by hydrogen peroxide (H₂O₂) in the human SH-SY5Y cell line were studied. Methods: The methanolic extraction of barberry root was performed using a maceration procedure. Oxidative stress was induced in SH-SY5Y cells by H₂O₂, and an MTT assay was applied to evaluate the neuroprotective effects of berberine and barberry root extract. The cells were pretreated with the half maximal inhibitory concentration (IC₅₀) of each compound (including berberine, barberry root extract, and H₂O₂), and the anti-apoptotic effects of all components were investigated using RT-PCR. Results: The SH-SY5Y cell viability increased in both groups exposed to 75 and 150 ppm barberry extract compared with that in the H₂O₂-treated group. The data showed that exposing SH-SY5Y cells to 30 ppm berberine significantly increased the cell viability compared with the H₂O₂-treated group; treatment with 150 and 300 ppm berberine and H₂O₂ significantly decreased the SH-SY5Y cell viability and was associated with berberine cytotoxicity. The mRNA levels of Bax decreased significantly under treatment with berberine at 30 ppm compared with the control group. A significant increase in Bcl-2 expression was observed only after treatment with the IC₅₀ of berberine. The expression level of Bcl-2 in cells exposed to both berberine and barberry extracts was also significantly higher than that in cells exposed to H₂O₂. Conclusion: The outcomes of this study suggest that treatment of SH-SY5Y cells with barberry extract and berberine could suppress apoptosis by regulating the actions of Bcl-2 family members.

• Food Science and Preservation
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• v.31 no.2
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• pp.276-286
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• 2024

In the present study, we investigated whether a mixture of fucoidan and Crepidiastrum denticulatum extract (FCE) had the potential to improve the therapeutic efficacy of cancer treatment. The results demonstrated that FCE significantly reduced cell viability and induced the release of LDH (lactate dehydrogenase) and DNA fragmentation in HepG2 cells in a dose-dependent manner. In addition, FCE treatment also increased the protein expression level of p53, the release of cytochrome c, and the loss of mitochondrial membrane potential. Moreover, FCE dose-dependently increased protein expression levels of Bax, and cleaved caspase-3 and -9. However, FCE decreased the protein expression level of Bcl-2. These results suggest that FCE inhibits cell proliferation and induces apoptosis via the mitochondrial-mediated intrinsic pathway. The present study demonstrates that FCE can be used as an anti-cancer agent for liver cancer based on apoptosis mechanism.