• The Korean Journal of Physiology and Pharmacology
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• 제5권5호
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• pp.381-388
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• 2001

This work describes the pharmacological inhibition by KR 31378 and its acetyl metabolite, KR 31612, of the apoptotic cell death induced by $H_2O_2$ in the A7r5 cells. Exposure of A7r5 cells to $H_2O_2$ (0.5 mM) induced a concentration-dependent cytotoxicity in association with oligonucleosomal DNA fragmentation. $H_2O_2-induced$ cell death was potently suppressed by KR 31378, KR 31612, ${\alpha}-tocopherol$ or trolox. Additionally, the apoptotic death of A7r5 cells (DNA ladders on electrophoresis) was also strongly suppressed by KR 31378 and KR 31612, but to a less degree by ${\alpha}-tocopherol$ and trolox. As a mechanistic study, incubation with $H_2O_2$ markedly showed a decreased Bcl-2 level and, in contrast, increased Bax protein and cytochrome C release, which were significantly and concentration-dependently reversed by KR 31378 and KR 31612 as well as by ${\alpha}-tocopherol$ and trolox. KR 31378 and ${\alpha}-tocopherol$ significantly reduced lipid peroxidation in accordance with reduced intracellular ROS and peroxyl radical. These results suggest that KR 31378 has a therapeutic potential against the apoptotic injury via mediation of anti- oxidative stress.

• 동의생리병리학회지
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• 제26권3호
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• pp.287-292
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• 2012

The results of this study intended to clarify the apoptotic effects of curcumin on Epstein-Barr virus transformed human B lymphoma (EBV-B) cells are summarized as follows: It was found that curcumin induced endoplasmic reticulum(ER) stress as well as apoptotic cell death in EBV-B cells, although the magnitude of action was insignificant. When EBV-B cells activated by pokeweed mitogen (PWM) were treated with the same concentrations of curcumin, it was found that higher ER stress (GRP78, P-PERK, XBP-1, ATF6, and CHOP expressed) increased unfold protein response (UPR) and thus, apoptosis attributed to ER stress, compared to non-activated EBV-B cells In conclusion, it is expected that curcumin will play an important role for leukemia treatment.

• Animal cells and systems
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• 제4권4호
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• pp.347-352
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• 2000

Programmed cell death, apoptosis, is a mechanism to maintain tissue homeostasis. Although the apoptotic process in rodent mammary tissues has been known to occur at the onset of involution, little is known about programmed cell death in the bovine tissues. Therefore, the purpose of this study was to investigate the molecular and cellular basis of apoptotic process in bovine mammary cells. Mammary tissues were obtained at different lactational and involurional stages. By apoptosis in situ endlabeling assay, apoptotic cells were found around the acinar celt lining in regressing bovine mammary tissues. The apoptosis-related genes bel-2 and bax were detected throughout involution by Northern blotting assay. The level of bax mRNA was dominantly expressed during involution. On the other hand, the bel-2 RNA transcripts were constantly expressed by 14 of post-lactation and declined thereafter. The expression of the testosterone-repressed prostate message-2 (TRPM-2) RNA transcripts, a marker for tissue remodeling, was increased as involution progressed. TNF a, were induced the DNA fragmentation and enhanced the expression of bax mRNA. In addition, milk protein secretion and amino acid uptake were decreased in mammary acinar culture treated with TNF $\alpha$. These results indicate that bovine mammary cells undergo apoptotic process after the cessation of milking and that TNF $\alpha$ may trigger apoptosis in lactating bovine mammary acini.

• Parasites, Hosts and Diseases
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• 제42권4호
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• pp.205-208
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• 2004

Neutrophils are important effector cells against protozoan extracellular parasite Entamoeba histolytica, which causes amoebic colitis and liver abscess in human beings. Apoptotic cell death of neutrophils is an important event in the resolution of inflammation and parasite's survival in vivo. This study was undertaken to investigate the ultrastructural aspects of apoptotic cells during neutrophil death triggered by Entamoeba histolytica. Isolated human neutrophils from the peripheral blood were incubated with or without live trophozoites of E. histolytica and examined by transmission electron microscopy (TEM). Neutrophils incubated with E. histolytica were observed to show apoptotic characteristics, such as compaction of the nuclear chromatin and swelling of the nuclear envelop. In contrast, neutrophils incubated in the absence of the amoeba had many protrusions of irregular cell surfaces and heterogenous nuclear chromatin. Therefore, it is suggested that Entamoeba-induced neutrophil apoptosis contribute to prevent unwanted tissue inflammation and damage in the amoeba-invaded lesions in vivo.

• 동의생리병리학회지
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• 제17권3호
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• pp.751-758
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• 2003

In our previous studies, we reported that Selaginella Tamariscina(ST) induced apoptotic cell death in HL-60 cells selectively. The cell viability after treatment with extract of ST was quantified by MTT assay and trypan bleu exclusion method. The results showed that application with ST in HL-60 induced 40% cell death at the concentration of 400 ㎍/ml. The cancericidic effect of Selaginella Tamariscina was mediated by apoptosis. Thus, HL-60 cells exposed to Selaginella Tamariscina displayed the DNA fragmentation ladder and nucleus chromatin condensation characteristic for apoptosis. The enzyme activity of caspase-3 and actived caspase-3 protein were markedly increased in HL-60 cells treated with the extract of Selaginella Tamariscina. In addition, the extract of Selaginella Tamariscina induced cleavage of PARP, a known substrate for caspase-3. The expression of Bcl-2, anti-apoptotic protein, was decreased by treatment of the aqueous extract of Selaginella Tamariscina in a dose-dependent manner. And the expression of pro-apoptotic Bax protein was increased. In conclusion, our results suggest that the extract of Selaginella Tamariscina may induce the apoptotic death of HL-60 cells via activation of caspase-3, cleavage of PARP protein, depletion of cellular ATP levels and Bcl-2 degradation.

• 동의생리병리학회지
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• 제20권6호
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• pp.1459-1466
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• 2006

The water extract of Hwansodan has been traditionally used for treatment of ischemic brain damage in oriental medicine. However, little is known about the mechanism by which the water extract of Hwansodan rescues cells from neurodegenerative disease. PC12 pheochromocytoma cells have been used extensively as a model for studying the cellular and molecular mechanisms of neuronal cell damages. Under deprivation of growth factor and ischemic injury, PC12 cells spontaneously undergoes apoptotic cell death. Serum and glucose deprivation markedly decreased the viability of PC12 cells, which was characterized with apparent apoptotic features such as membrane blebbing as well as fragmentation of genomic DNA and nuclei. However, the aqueous extract of Hwansodan significantly reduced serum and glucose deprivation-induced cell death and apoptotic characteristics through reduction of intracellular peroxide generation. Pretreatment of Hwansodan also ingibited the activation of caspase-3, in turn, degradation of ICAD/DFF45 was completely abolished in serum and glucose deprivated cells. Furthermore, pretreatment of Hwansodan obviously increased heme oxygenase 1 (HO-1) expression in PC12 cells. Taken together, the data suggest that the protective effects of Hwansodan against serum and glucose deprivation induced oxidative injuries may be achieved through the scavenging of reactive oxygene species accompanying with HO-1 induction.

• 동의생리병리학회지
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• 제20권6호
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• pp.1584-1592
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• 2006

Houttuynia cordata Thunb, well known as 'E-Sung-Cho' in Korea, is traditional medicinal plant generally used in Oriental medicine therapy. We previously reported that the water extract of H. cordata inhibited cell proliferation and induced apoptosis in human breast carcinoma cells. In the present study, we investigated the biochemical mechanisms of anti-proliferative effects by the methanol extract of H. cordata (MEHC) in human lung carcinoma A549 cells. It was found that MEHC could inhibit the cell growth in a dose-dependent manner, which was associated with morphological change and apoptotic cell death as determined by formation of apoptotic bodies, DNA fragmentation and increased populations of apoptotic-sub G1 phase cells. Apoptosis of A549 cells by MEHC was also connected with a down-regulation of anti-apoptotic Bcl-2 and inhibitor of apoptosis proteins (IAPs) expression. MEHC treatment induced the proteolytic activation of caspase-3, caspase-8 and caspase-9, and a concomitant inhibition of poly(ADP-ribose) polymerase (PARP), ${\beta}$-catenin and phospholipase (PLC)-${\gamma}$1 protein expression. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of H. cordata.

• Molecules and Cells
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• 제42권12호
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• pp.884-892
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• 2019

Piperlongumine (PL), a natural alkaloid compound isolated from long pepper (Piper longum), can selectively kill cancer cells, but not normal cells, by accumulation of reactive oxygen species (ROS). The objective of this study was to investigate functional roles of expression of SETDB1 and FosB during PL treatment in MCF7 breast cancer cells. PL downregulates SETDB1 expression, and decreased SETDB1 expression enhanced caspase 9 dependent-PARP cleavage during PL-induced cell death. PL treatment generated ROS. ROS inhibitor NAC (N-acetyl cysteine) recovered SETDB1 expression decreased by PL. Decreased SETDB1 expression induced transcriptional activity of FosB during PL treatment. PARP cleavage and positive annexin V level were increased during PL treatment with FosB overexpression whereas PARP cleavage and positive annexin V level were decreased during PL treatment with siFosB transfection, implying that FosB might be a pro-apoptotic protein for induction of cell death in PL-treated MCF7 breast cancer cells. PL induced cell death in A549 lung cancer cells, but molecular changes involved in the induction of these cell deaths might be different. These results suggest that SETDB1 mediated FosB expression may induce cell death in PL-treated MCF7 breast cancer cells.

• 한국임상수의학회지
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• 제23권2호
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• pp.144-148
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• 2006

Apoptotic death of articular chondrocytes has been implicated in the pathogenesis of osteoarthritis. Tartrate resistant acid phosphatase (TRAP) has been used for several years as a marker enzyme of bone-resorbing osteoclasts. This study investigated the activity of TRAP in media of apoptotic cell death-induced canine chondrocyte. We exposed canine chondrocyte to capsaicin and the results showed that capsaicin induced cell death in a dose dependent manner. And we measured TRAP activity in media of chondrocyte death induced by capsaicin treatment and the results capsaicin significantly increased the activity of TRAP in media for dose dependent. We also investigated whether the combination treatment with capsaicin and TRAIL enhance apoptotic cell death in canine chondrocyte. We exposed canine chondrocyte to capsaicin for 24 hrs at the indicated dose, and then treated with recombinant TRAIL protein for 24 hrs. TRAIL alone did not induce cell death after 24 hours, but the combined treatment of both induced more cell death compared with capsaicin alone in a dose dependent manner. Also, the combination treatment with capsaicin and TRAIL increased the activity of TRAP in culture media. These results suggest that TRAP can flow out into extracellular after chondrocyte damage, and TRAP may be a successful biomarker for detection of joint disease such as osteoarthritis.

• Journal of Acupuncture Research
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• 제31권2호
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• pp.87-98
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• 2014

Objectives : We investigated whether snake venom toxin(SVT) from Vipera lebetina turanica sensitizes HT29 human epithelial colorectal cancer cells to tumor necrosis factor(TNF)-related apoptosis-inducing ligand(TRAIL) induced apoptosis in cancer cells. Methods : Cell viability assay was used to assess the inhibitory effect of TRAIL on cell growth of HT29 human colorectal cancer cells. And 6-diamidino-2-phenylindole(DAPI), terminal deoxynucleotidyl transferase mediated dUTP nick end labeling assay(TUNEL) staining assay were used to evaluate cell-apoptosis. Western blot analysis were conducted to observe apoptosis related proteins and death receptor. To assess whether the synergized inhibitory effect of SVT and TRAIL on reactive oxygen species(ROS) generation was reversed by strong anti-oxidative agent. Results : SVT with TRAIL inhibited HT29 cell growth different from TRAIL alone. Consistent with cell growth inhibition, the expression of TRAIL receptors; Expression of death receptor(DR)4 and DR5 was significantly increased and intrinsic pro-apoptotic cleaved caspase-3, -9 was subsequently increased together with increase of Bax/Bcl-2 ratio and extrinsic pro-apototic caspase-8 was also activated. In addition, the expression of anti-apoptotic survival proteins, a marker of TRAIL resistance(eg, cFLIP, survivin, X-linked inhibitor of apoptosis protein(XIAP) and Bcl-2) was suppressed by the combination treatment of SVT and TRAIL. Pretreatment with the ROS scavenger N-acetylcysteine abolished the SVT and TRAIL-induced upregulation of DR4 and DR5 expression and expression of the intrinsic pro-apoptotic caspase-3 and-9. Conclusion : The collective results suggest that SVT facilitates TRAIL-induced apoptosis in $HT_{29}$ human epithelial colorectal cancer cells through up-regulation of the TRAIL receptors; DR4 and DR5 and consecutive induction of bilateral apoptosis via regulating apoptosis related proteins.