• BMB Reports
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• v.35 no.5
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• pp.452-458
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• 2002

Exposure to ultraviolet light (UV) induces apoptosis in mammalian cells, The caspase group of proteases is required for the appotosis. This pathway is initiated by a release of cytochrome c from the mitochondria into the cytosol. Several Bcl-2 family proteins can regulate the release of cytochrome c by stabilizing the mitochondrial membrane. Here we show that expression of the endogenous bcl-xL was strongly downregulated in NIH3T3 cells within 2 h after UV-C irradiation, and that of bax was upregulated from 8 h after irradiation. Apoptosis was induced in more than 50% of the NIH3T3 cells 48 h after irradiation. Constitutive overexpression of bcl-xL in NIH3T3 cells protected the UV-induced apoptosis by preventing the loss of mitochondrial membrane potential and the activation of caspase 9. There results suggest that downregulation of Bcl-xL is relevant to UV-induced apoptosis of tibroblasts.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.9
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• pp.1114-1119
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• 2008

Among the numerous polyphenols isolated from green tea, epigallocatechin gallate (EGCG) is a predominate and is considered to be a major therapeutic agent. To elucidate the mechanical insights of anti-tumor effect, EGCG was applied to human breast cancer MDA-MB-231 cells. We investigated the effect of EGCG on protein and mRNA expression of proteins related to cell apoptosis in MDA-MB-231 human breast cancer cell lines. We also identified caspase-3 activity. We cultured MDA-MB-231 cells in the presence of 0, 5, 10, and $20\;{\mu}M$ of EGCG. Protein and mRNA expression of bcl-2 were decreased dose-dependently in cells treated with EGCG. However, protein and mRNA expression of bax were increased (p<0.05). Caspase-3 activities were increased dose-dependently in cells treated with EGCG. These results suggest that EGCG induces cell apoptosis by increase of caspase activity through decreasing of protein and mRNA expression of bcl-2 and increasing of protein and mRNA expression of bax.

• Tuberculosis and Respiratory Diseases
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• v.56 no.5
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• pp.450-464
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• 2004

Background : The FHIT (fragile histidine triad) gene is a frequent target of deletions associated with abnormal RNA and protein expression in lung cancer. Previous studies have shown FHIT gene transfer into lung cancer cell line lacking FHIT protein expression resulted in inhibition of tumor cell growth attributable to the induction of apoptosis and reversion of tumorigenecity. However, the mechanism of the tumor suppressor activity of the FHIT gene and the cellular pathways associated with its function are not completely understood. Methods : To gain insight into the biological function of FHIT, we compared the NCI-H358 cell line with its stable FHIT transfectants after treatment with cisplatin or paclitaxel. We investigated the effects of FHIT gene expression on cell proliferation, apoptosis, and activation of caspase system and Bcl-2 family. The induction of apoptosis was evaluated by using DAPI staining and flow cytometry. Activation of caspases and Bcl-2 members was evaluated by Western blot analysis. Results : A significantly increased cell death was observed in FHIT transfectants after cisplatin or paclitaxel treatment and this was attributable to the induction of apoptosis. Remarkable changes in caspases and Bcl-2 family were observed in the transfected cells as compared with the control cells after treatment with paclitaxel. Activation of caspase-3 and caspase-7 was markedly increased in cells expressing FHIT. Expression level of Bcl-2 and Bcl-xL protein was significantly decreased and that of Bax and Bad protein was significantly increased in the transfected cells. Conclusion : FHIT gene delivery into lung cancer cells results in enhanced apoptosis induced by treatment with cisplatin or paclitaxel. The data suggest that apoptosis in FHIT-expressing cells could be related to activation of caspase pathway and Bcl-2 family.

• Journal of Life Science
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• v.26 no.8
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• pp.887-894
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• 2016

The extract from Artemisia annuain L.(AAE) is known as a medicinal herb that is effective against cancer. Apoptosis is the process of programmed cell death, and mitochondria are known to play a central role in cell death control. In this study, we evaluated the p53-independent apoptosis of extract of AAE through downregulation of Bcl-2 and the mitochondrial pathway in A549 (lung cancer cells). AAE may exert cancer cell apoptosis through regulating p-Akt, Cox-2, p53 and mitochondria-mediated apoptotic proteins. p-Akt/cox-2 is known to play an important role in cell proliferation and cell survival. The Bcl-2 pro-apoptotic proteins (such as Bax, Bak and Bim) mediate the permeabilization of the mitochondrial outer membrane. Treatment of AAE reduces p-Akt, p-Mdm2, cox-2 and anti-apoptotic proteins (such as Bcl-2), while tumor suppressor p53 and pro-apoptotic proteins. Activation of Bax/Bak releases cytochrome c from mitochondria to the cytosol to activate a caspase. Caspase-3 is the major effector caspase associated with apoptotic pathways. Caspase-3 generally exists in cytoplasm in the form of a pro-enzyme. In the initiation stage of apoptosis, caspase-3 is activated by proteolytic cleavage and activated caspase-3 cleaves poly (ADP-ribose) polymerase (PARP). We treated Pifithrin-α (p53 inhibitor) and Celecoxib (Cox-2 inhibitor) to learn the relationship between the signal transduction of proteins associated with apoptosis. These results suggest that AAE induces apoptosis through a p53-independent pathway in A549.

• Korean Journal of Biological Psychiatry
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• v.5 no.2
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• pp.219-226
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• 1998

Cytosine arabinoside(AraC) inhibits DNA synthesis and ${\beta}$-DNA polymerase, an enzyme involved in DNA repair. This, a potent antimitotic agent, is clinically used as an anticancer drug with side effect of severe neurotoxicity. Earlier reports suggested that inhibition of neuronal survival by AraC in sympathetic neuron may be due to the inhibition of a 2'-deoxycytidine-dependent process that is independent of DNA synthesis or repair and AraC induced a signal that is triggers a cascade of new mRNA and protein synthesis, leading to apoptotic cell death in cultured cerebellar granule cells. The present study would suggest whether caspase family(ICE/CED-3-like protease) involved in AraC-induced apoptosis pathway of PC12 cells. It was observed that treatment of PC12 cells with AraC led to decrease of viability by MTT assay and morphology changes, which did not suggest that AraC induced apoptosis in PC12 cells. The mRNA of caspase-1/caspase-3 were expressed in PC12 cells constitutively, and AraC did not activate caspase family. These results suggest that caspase-1/caspase-3 may not be required for AraC-induced cell death pathway in PC12 cells.

• BMB Reports
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• v.45 no.2
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• pp.85-90
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• 2012

Our previous study demonstrated that CopA3, a disulfide dimer of the coprisin peptide analogue (LLCIALRKK), has antibacterial activity. In this study, we assessed whether CopA3 caused cellular toxicity in various mammalian cell lines. CopA3 selectively caused a marked decrease in cell viability in Jurkat T, U937, and AML-2 cells (human leukemia cells), but was not cytotoxic to Caki or Hela cells. Fragmentation of DNA, a marker of apoptosis, was also confirmed in the leukemia cell lines, but not in the other cells. CopA3-induced apoptosis in leukemia cells was mediated by apoptosis inducing factor (AIF), indicating induction of a caspase-independent signaling pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2133-2139
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• 2014

4-Methylsulfinyl-3-butenyl isothiocyanate (MTBITC) found in the radish (Raphanus sativus L.), is a wellknown anticancer agent. In this study, the mechanisms of the MTBITC induction of cell apoptosis in human A549 lung cancer cells were investigated. Our PI staining results showed that MTBITC treatment significantly increased the apoptotic sub-G1 fraction in a dose-dependent manner. The mechanism of apoptosis induced by MTBITC was investigated by testing the change of mitochondrial membrane potential (${\Delta}{\Psi}m$), the expression of mRNAs of apoptosis-related genes by RT-PCR, and the activities of caspase-3 and -9 by caspase colorimetric assay. MTBITC treatment decreased mitochondrial membrane potential by down-regulating the rate of Bcl-2/Bax and Bcl-xL/Bax, and activation of caspase-3 and -9. Therefore, mitochondrial pathway and Bcl-2 gene family could be involved in the mechanisms of A549 cell apoptosis induced by MTBITC.

• The Journal of Korean Medicine
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• v.26 no.4
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• pp.108-121
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• 2005

Backgrounds: Amygdalin (D-mandelonitrile B-gentiobioside), a cynogenic compound, is found in sweet and bitter almond, Persicae semen, and Armeniacae semen. Aqueous extract of amygdalin was made from Armeniacae semen and used in this study. Objectives: Apoptosis is a very important mechanism in cancer treatment. In the present study, it was investigated whether amygdalin induces apoptotic cell death in human COLO 201 colon cancer cells. Materials and Methods: For this study, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, 4,6diamidino-2-phenylindole (DAPI) staining, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay, flow cytometric analysis, reverse transcription-polymerase chain reaction(PR-PCR), western blot analysis, and caspase-3 enzyme assay were performed on COLO 201 cells. Cells treated with amygdalin exhibited several characteristics of apoptosis. Results: Amygdalin treatment enhanced Bax expression and suppressed Bcl-2 expression in COLO 201 cells. Amygdalin also was shown to increase the caspase-3 activity. Conclusions: Amygdalin induces apoptotic cell death via Bax-dependent caspase-3 activation in COLO 201 cells.

• Journal of the Korean Chemical Society
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• v.66 no.4
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• pp.298-304
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• 2022

The present study was designed to investigate the molecular mechanisms of DK-5-62, a novel (-)-catechin derivative on HCT116 human colorectal cancer cells. DK-5-62 inhibited the proliferation in dose- and time-dependent manner accompanied by the morphological changes. Effects of DK-5-62 appeared to be mediated by the induction of apoptosis, as manifested through DNA-binding dye Hoechst 33258 staining. Analysis of the mechanism of these events indicated that DK-5-62-treated cells exhibited an increased ratio of Bax/Bcl-2, resulting in the activation of caspase-9, caspase-3, and poly-ADP-ribose polymerase in a dose-dependent manner. Moreover, DK-5-62-induced apoptosis was accompanied by phosphorylation of the mitogen-activated protein kinase family, c-Jun N-terminal kinase, p38, and extracellular signal-regulated kinase. These results suggest that HCT116 cells are moderately sensitive to growth inhibition by DK-5-62 via apoptosis, as evidenced by activation of ERK/p38/Bcl-2 family signaling, as well as alteration in caspase-9 and caspase-3.

• Natural Product Sciences
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• v.26 no.3
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• pp.191-199
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• 2020

Fucoidan, a natural component of brown seaweed, has various biological activities such as anti-cancer activity, anti-oxidant, and anti-inflammatory against various cancer cells. However, the fucoidan has been implicated in melanoma cells via apoptosis signaling pathway. Therefore, we investigated apoptosis with fucoidan in A2058 human melanoma cells with dose- and time-dependent manners. In our results, A2058 cells viability decreased at relatively short-time and low-concentration through fucoidan. This effects of fucoidan on A2058 cells appeared to be mediated by the induction of apoptosis, as manifested by morphological changes through DNA-binding dye Hoechst 33342 staining. When a dose of 80 ㎍/mL fucoidan was treated, the cells were observed: crescent or ring-like structure, chromatin condensation, and nuclear fragmentation. With the increase at 100 ㎍/mL fucoidan, the cell membrane is intact throughout the total process, including membrane blebbing and loss of membrane integrity as well as increase of sub-G1 DNA. Furthermore, to understand the exact mechanism of fucoidan-treated in A2058 cells, western blotting was performed to detect apoptosis-related protein expression. In this study, Bcl-2 family proteins can be regulated by fucoidan, suggesting that fucoidan-induced apoptosis is modulated by intrinsic pathway. Therefore, expression of Bcl-2 and Bax may result in altered permeability, activating caspase-3 and caspase-9. And the cleaved form of poly ADP-ribose polymerase was detected in fucoidan-treated A2058 cells. These results suggest that A2058 cells are highly sensitive to growth inhibition by fucoidan via apoptosis, as evidenced by activation of extracellular signal-regulated kinases/p38/Bcl-2 family signaling, as well as alteration in caspase-9 and caspase-3.