• Molecules and Cells
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• v.23 no.1
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• pp.30-38
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• 2007

Dipyrithione (2, 2'-dithiobispyridine-1, 1'-dioxide, PTS2), a pyrithione derivate, is highly bactericidal and fungicidal. In this study we examined its apoptotic effect on HeLa cells. PTS2 induced HeLa cell death in a dose and time dependent manner. ERK1/2 and p38 were markedly activated, but little JNK1/2 activation was detected. Suppression of p38 activation by SB203580 reduced the extent of apoptosis of the HeLa cells and also prevented induction of p21, release of cytochrome c, and cleavage of caspase-3 and PARP. Inhibition of ERK1/2 with PD98059 increased apoptosis, indicating that ERK1/2 activation has an anti-apoptotic effect on PTS2-induced HeLa cell apoptosis. PTS2 also inhibited murine sarcoma 180 and hepatoma 22 tumor growth in an animal tumor model. Our findings indicate that PTS2 possesses anti-tumor activity, that caspase-3 and poly (ADP-ribose) polymerase (PARP) are involved in PTS2-induced HeLa cell apoptosis and that ERK1/2 and p38 have opposing effects on this apoptosis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.4
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• pp.745-755
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• 2002

To examine the effects of Yunpyesan on the cell proliferation of A549 human lung carcinoma cell line, we performed various experiments such as dose-dependent effect of Yunpyesan on cell proliferation and viability, morphological changes, quantification of apoptotic cell death and alterations of apoptosis/cell cycle-regulatory gene products. Yunpyesan declined cell viability and proliferation in both a dose- and a time-dependent manner. The anti-proliferative effect by Yunpyesan treatment in A459 cells was associated with morphological changes such as membrane shrinking and cell rounding up. Yunpyesan Induced apoptotic cell death in a time-dependent manner, which was associated with degradation of poly-(ADP-ribose) polymerase (PARP), an apoptotic target protein, without alterations of the balance between Bcl-2 and Bax expressions. DNA flow cytometric histograms showed that population of G1 phase of the cell cycle was increased by Yunpyesan treatment in a dose-dependent manner. Western blot analysis revealed that cyclin D1 and A were reduced by Yunpyesan treatment, whereas cyclin dependent kinase (Cdk) inhibitor p27 was markedly increased in a time-dependent fashion. The level of tumor suppressor p53 proteins was also increased by Yunpyesan treatment and its increase might be linked to increase of Cdk inhibitor p27. In addition, Mdm2, negative regulator of p53, was down-regulated by Yunpyesan treatment. Since the expression of retinoblastome protein (pRB), a key regulator of G1/S progression, was reduced by Yunpyesan treatment, we supposed that phosphorylation of pRB might be also blocked. The present results indicated that Yunpyesan-induced inhibition of lung cancer cell proliferation is associated with the induction of apoptosis and the blockage of G1/S progression.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.2
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• pp.553-560
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• 2004

In the present study, we investigated the anti-proliferative effects of aqueous extract of Wikyung-tang(WKT) on the growth of human lung carcinoma cell line A549. WKT treatment declined the cell viability and proliferation of A549 cells in a concentration-dependent manner. The anti-proliferative effects by WKT treatment in A549 cells was associated with morphological changes such as membrane shrinking and cell rounding up. WKT treatment induced an inhibition and/or degradation of apoptotic target proteins such poly(ADP-ribose) polymerase (PARP) and phospholipase C-γ1 (PLC-γ1). WKT treatment did not affect the levels of other Bcl-2 family gene products, such as Bcl-2, Bax and Bad. Western blot analysis and RT-PCT data revealed that the levels of tumor suppressor p53 and cyclin-dependent kinase inhibitor p21 were induced by WKT treatment in A549 cells. Additionally, WKT treatment induced the down-regulation of telomerase reverse transcriptase mRNA (hTERT) expression of A549 cells, however, the levels of other telomere-regulatory gene products were not affected. Taken together, these findings suggest that WKT-induced inhibition of human lung cancer cell proliferation is associated with the induction of apoptotic cell death via regulation of several major growth regulatory gene products and WKT may have therapeutic potential in human lung cancer.

• Journal of Microbiology and Biotechnology
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• v.30 no.6
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• pp.885-892
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• 2020

Chemotherapy regimens for non-small cell lung cancer (NSCLC) have various adverse effects on the human body. For this reason, probiotics have received attention regarding their potential value as a safe and natural complementary strategy for cancer prevention. This study analyzed the anticancer effects of aqueous extracts of probiotic bacteria Bifidobacterium bifidum (BB), Bifidobacterium longum (BL), Bifidobacterium lactis (BLA), Bifidobacterium infantis 1 (BI1), and Bifidobacterium infantis 2 (BI2) on NSCLC cell lines. When the aqueous extracts of probiotic Bifidobacterium species were applied to the NSCLC cell lines A549, H1299, and HCC827, cell death increased considerably; in particular, the aqueous extracts from BB and BLA markedly reduced cell proliferation. p38 phosphorylation induced by BB aqueous extract increased the expression of cleaved caspase 3 and cleaved poly (ADP-ribose) polymerase (PARP), consequently inducing the apoptosis of A549 and H1299 cells. When the p38 inhibitor SB203580 was applied, phosphorylation of p38 decreased, and the expression of cleaved caspase 3 and cleaved PARP was also inhibited, resulting in a reduction of cell death. In addition, BB aqueous extracts reduced the secretion of MMP-9, leading to inhibition of cancer cell invasion. By contrast, after transfection of short hairpin RNA shMMP-9 (for a knockdown of MMP-9) into cancer cells, BB aqueous extracts treatment failed to suppress the cancer cell invasiveness. According to our results about their anticancer effects on NSCLC, probiotics consisting of Bifidobacterium species may be useful as adjunctive anticancer treatment in the future.

• Journal of Microbiology and Biotechnology
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• v.16 no.8
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• pp.1262-1268
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• 2006

In the search for a novel cytotoxic substance from medicinal plants, HY53 ($C_{17}H_{32}O_2N_2$; molecular weight 296) was isolated from the leaves of Pata de Vaca (Bauhinia forficata). The growth of the HepG2 cells was inhibited in a dose-dependent manner when treated with 0.07 to 0.40 mM HY53 for 24 h (IC$_{50}$: 0.13 mM). Furthermore, nuclear DAPI staining revealed the typical nuclear features of apoptosis in the HepG2 cells exposed to 0.27 mM HY53, whereas a flow cytometric analysis of the HepG2 cells using propidium iodide showed that the apoptotic cell population increased gradually from 8% at 0 mM to 23% at 0.14 mM and 45% at 0.40 mM after being exposed to each concentration of HY53 for 24 h. Moreover, a TUNEL assay also exhibited the apoptotic induction of the HepG2 cells treated with HY53. To obtain further information on the HY53-induced apoptosis, the expression level of certain apoptosis-associated proteins was examined using a Western blot analysis. Treatment of the HepG2 cells with HY53 resulted in the activation of caspase-3, and subsequent proteolytic cleavage of poly(ADP-ribose) polymerase (PARP). Consequently, the results confirmed that the apoptosis in the HepG2 cells was induced by HY53 and the involvement of caspase-3-mediated PARP cleavage in the apoptotic process.

• Journal of Microbiology and Biotechnology
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• v.12 no.6
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• pp.950-956
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• 2002

The antitumor activity of the insect pathogenic fungus Paecilomyces japonica has been attributed to apoptotic cell death. However, the mechanism underlying the induced apoptosis has not yet been elucidated. In this study, we for the first time show that mitochondria-dependent caspase-3 activation were associated with the apoptotic activity of P. japonica in human acute leukemia Jurkat T cells. When Jurkat T cells were treated with the ethyl acetate extract of P japonica at concentrations ranging from $2-6{\mu}g/ml$, apoptotic cell death. accompanied by several biochemical events such as caspase-9 activation, caspase-3 activation, degradation of poly (ADP-ribose) polymerase (PARP), and apoptotic DNA fragmentation, was induced in a dose-dependent manner. In addition, the release of cytochrome c from mitochondria was detected. Under these conditions, the expression of Fas and Fas-ligand (FasL) remained unchanged. Ethyl acetate extract-induced mitochondrial cytochrome c release, caspase-3 activation, PARP cleavage, and apoptotic DNA fragmentation were suppressed by the ectopic expression of Bcl-2, which is known to block mitochondrial cytochrorme c release. Accordingly, these results demonstrate that P. japonica-induced apoptotic cell death is mediated by a cytochrome c-dependent caspase-3 activation pathway that can be interrupted by Bcl-2.

• Biomedical Science Letters
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• v.19 no.3
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• pp.195-205
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• 2013

Obesity may cause metabolic syndrome and adult diseases. This study was undertaken to investigate the ameliorative or useful effects of beanleaves on inflammation and liver damage in obese rat models. Rats were divided into three groups: a control group (normal diet, n=6), a fat diet group (45%-fat diet, n=7), and a bean leaf group (45%-fat+Korean bean leaves diet, n=7). Body weights in the bean leaf group were lower than those of the fat group (P<0.05). Serum tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and prostaglandin $E_2$ ($PGE_2$) concentrations were lower in both the control and bean leaf groups than in the fat group (P<0.001). TNF-${\alpha}$ concentrations in the bean leaf group were slightly higher than in the control group but statistically significant (P<0.05). The bean leaf group histologically exhibited lower fatty degeneration, spotty necrosis, and leukocyte infiltrations in hepatic tissues than those of the fat group. In the homogenized liver tissues, the cyclooxygenase-2 (COX-2) gene was only expressed in the fat group. The gene expression levels of hepatic TNF-${\alpha}$, inducible nitric-oxide synthase, peroxiome proliferator-activated receptor-${\alpha}$ (PPAR-${\alpha}$), poly (ADP-ribose) polymerase (PARP), and transforming growth factor-${\beta}1$ (TGF-${\beta}1$) were weaker in the bean leaf group than in the fat group. These results suggest that adding bean-leaves to the diet may ameliorate obesity-induced systemic inflammation and liver damage and that bean leaves may be a useful food for preventing obesity and thereby metabolic syndrome and adult diseases.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.3
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• pp.677-683
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• 2003

We investigated the effects of Insamsapye-tang (ISSPT) water extract on the growth of human lung carcinoma A549 cells. Upon treatment with ISSPT extract, a concentration-dependent inhibition of cell viability was observed and cells developed many of the hallmark features of apoptosis, including condensation of chromatin. Flow cytometry analysis confirmed that ISSPT treatment increased populations of apoptotic-sub G1 phase. In addition, proteolytic degradation of poly(ADP-ribose) polymerase (PARP) and β-catenin protein were observed after treatment of ISSPT extract. These apoptotic effects of ISSPT in A549 cells were associated with marked inhibition of Bel-xL expression in a dose-dependent manner, however the levels of Bcl-2 and Bax expression were not affected. ISSPT treatment also induced the expression of tumor suppressor p53 mRNA and inhibited the expression of caspase-3 mRNA. The previous and present results indicated that ISSPT-induced inhibition of lung cancer cell proliferation is associated with the blockage of G1/S progression and the induction of apoptosis.

• Herbal Formula Science
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• v.13 no.2
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• pp.111-123
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• 2005

The purpose of this study was to investigate the anticancer effects of Caesalpiniae Lignum (Somok) on HepG2 cells, a human liver cancer cell line. To study the cytotoxic effect of Caesalpiniae Lignum methanol extract (CL-MeOH) on HepG2 cells, the cells were treated with various concentrations of CL-MeOH and then cell viability was determined by XTT reduction method and trypan blue exclusion assay. CL-MeOH reduced proliferation of HepG2 cells in a dose-dependent manner. To confirm the induction of apoptosis, HepG2 cells were treated with various concentrations of CL-MeOH. The activation of caspase 3 and the cleavage of poly ADP-ribose polymerase (PARP), a substrate for caspase-3 and a typical sign of apoptosis, was examined by western blot analysis. CL-MeOH decreased procaspase 3 level in a dose-dependent manner and induced the clevage of PARP at concentration> $200{\mu}/ml$. Mitogen-activated protein (MAP) kinase signaling cascades are multi-functional signaling networks that influence cell growth, differentiation, apoptosis, and cellular responses to stress. CL-MeOH-induced MAPK activation was examined by Western blot for phosphorylated ERK, p38 and JNK. CL-MeOH significantly increased p38 phosphorylation and JNK phosphorylation in a dose-dependent manner. Inhibition of p38 function using the selective inhibitor SB20358O results in inhibition of apoptosis by CL-MeOH. These results suggest that CL-MeOH-induced apoptosis is MAP kinase-dependent apoptoric pathway. These results suggest that CL-MeOH is potentially useful as a chemotherapeutic agent in human liver cancer.

• Journal of Korean society of Dental Hygiene
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• v.20 no.5
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• pp.763-771
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• 2020

Objectives: Erigeron bonariensis is a type of Erigeron found throughout the tropical and subtropical areas as one of the perennial plants or pioneer plants. It is known to show detoxifying, antipyretic, and anticancer effects for various cancers. However, there are no reports on the anticancer effect of E. bonariensis on oral cancer cells. In the present study, we investigated the effects of the methanol extract of Erigeron bonariensis (MEEB) on the inhibition of cell growth and induction of apoptosis in mucoepidermoid carcinoma (MEC) cell lines, including the MC3 and YD15 oral cancer cells. Methods: MC3 Cells were treated by dimethyl sulfoxide (DMSO) or methanol extracts of 20 various natural products 20 ㎍/mL for 48 hours and cell viability were analyzed as Trypan blue exclusion assay. The effects of MEEB treatment on the cell viability of MC3 and YD15 cells, for 48 h, were analyzed by Trypan blue exclusion assay. The anticancer efficacy and apoptosis of oral cancer cell lines were analyzed by western blot analysis. The statistical significance of differences between groups was analyzed by Student's two-tailed t-test. A value of P<0.05 compared to the vehicle control was considered statistically significant. Results: Among 20 different naturally derived products, MEEB significantly inhibited cell viability and increased cleaved poly [ADP-ribose] polymerase 1 (PARP) protein in the MC3 and YD15 cells in a concentration-dependent manner. Conclusions: These results suggest that MEEB can be used as a natural anticancer drug for the treatment of human oral cancer.