• BMB Reports
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• v.48 no.3
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• pp.166-171
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• 2015

We previously demonstrated that resveratrol and clofarabine elicited a marked cytotoxicity on malignant mesothelioma (MM) MSTO-211H cells but not on the corresponding normal mesothelial MeT-5A cells. Little is known of the possible molecules that could be used to predict preferential chemosensitivity on MSTO-211H cells. Resveratrol and clofarabine induced downregulation of Mcl-1 protein level in MSTO-211H cells. Treatment of cells with cycloheximide in the presence of proteasome inhibitor MG132 suggested that Mcl-1 protein levels were regulated at the post-translational step. The siRNA-based knockdown of Mcl-1 in MSTO-211H cells triggered more growth-inhibiting and apoptosis-inducing effects with the resultant cleavages of procaspase-3 and its substrate PARP, increased caspase-3/7 activity, and increased percentage of apoptotic propensities. However, the majority of the observed changes were not shown in MeT-5A cells. Collectively, these studies indicate that the preferential activation of caspase cascade in malignant cells might have important applications as a therapeutic target for MM.

• Journal of Astronomy and Space Sciences
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• v.24 no.1
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• pp.39-44
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• 2007

We report photometric features of the HB, MSTO, and SGB for a set of metal-poor Galactic globular clusters on the near-IR CMDs. The magnitude and color of the MSTO and SGB are measured on the fiducial normal points of the CMDs by applying a polynomial fit. The near-IR luminosity functions of horizontal branch stars in the classical second parameter pair M3 and M13 indicate that HB stars in M13 are dominated by hot stars that are rotatively faint in the infrared, whereas HB stars in M3 are brighter than those in M13. The luminosity functions of HB stars in the observed bulge clusters, except for NGC 6717, show a trend that the fainter hot HB stars are dominated in the relatively metal-poor clusters while the relatively metal-rich clusters contain the brighter HB stars. It is suggestive that NGC 6717 would be an extreme example of the second-parameter phenomenon for the bulge globular clusters.

• Biomolecules & Therapeutics
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• v.20 no.3
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• pp.273-279
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• 2012

Hesperidin, a flavanone present in citrus fruits, has been studied as potential therapeutic agents that have anti-tumor activity and apoptotic effects in several cancers, but there is no report about the apoptotic effect of hesperidin in human malignant pleural mesothelioma through the specificity protein 1 (Sp1) protein. We investigated whether hesperidin inhibited cell growth and regulated Sp1 target proteins by suppressing the levels of Sp1 protein in MSTO-211H cells. The $IC_{50}$ value of hesperidin was determined to be 152.3 ${\mu}M$ in MSTO-211H cells for 48 h. Our results suggested that hesperidin (0-160 ${\mu}M$) decreased cell viability, and induced apoptotic cell death. Hesperidin increased Sub-$G_1$ population in MSTO-211H cells. Hesperidin significantly suppressed mRNA/protein level of Sp1 and modulated the expression level of the Sp1 regulatory protein such as p27, p21, cyclin D1, Mcl-1, and survivin in mesothelioma cells. Also, hesperidin induced apoptotic signaling including: cleavages of Bid, caspase-3, and PARP, upregulation of Bax, and down-regulation of Bcl-$_{xl}$ in mesothelioma cells. These results show that hesperidin suppressed mesothelioma cell growth through inhibition of Sp1. In this study, we demonstrated that Sp1 acts as a novel molecular target of hesperidin in human malignant pleural mesothelioma.

• Bulletin of the Korean Space Science Society
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• 2004.04a
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• pp.89-89
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• 2004

It is believed that age controls horizontal-branch (HB) morphology of Globular Clusters besides metallicity (first parameter). However, other second parameter candidates, such as He abundance and alpha elements enhancement, could also affect HB morphology. These effects may influence to the age measurements from the main-sequence turnoff (MSTO) as well. We will measure the variations of age caused by each second parameter candidate at HB and MSTO respectively, using the well known second parameter pair M3 and Ml3. (omitted)

• Journal of The Korean Astronomical Society
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• v.36 no.1
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• pp.13-19
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• 2003

We present a study of the old open cluster Trumpler 5 (Tr 5), based on the CDS archival data. From the color-magnitude diagrams of Tr 5, we have found the positions of main-sequence turn-off (MSTO) and red giant clump (RGC) stars. Using the mean magnitude of the RGC stars, we have estimated the reddening toward Tr 5, E(B - V) = 0.60 $\pm$ 0.10. Using the stars common in two data sets and the theoretical isochrones of Padova group, we have estimated the distance modulus $V_o - M_v = 12.64 {\pm} 0.20 (d = 3.4 {\pm} 0.3 kpc)$, the metallicity [Fe/H) = -0.30 $\pm$ 0.10, and the age of 2.4 $\pm$ 0.2 Gyr (log t = 9.38). These metallicity and distance values are consistent with the relation between the metallicity and the Galactocentric distance of other old open clusters, for which we obtain the slope of ${\Delta}[Fe/H]/ R_{gc} = -0.064 {\pm} 0.010\;dex\;kpc^{-1}$.

• BMB Reports
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• v.45 no.11
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• pp.647-652
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• 2012

We previously reported that MSTO-211H cells have a higher capacity to regulate Nrf2 activation in response to changes in the cellular redox environment. To further characterize its biological significance, the response of Nrf2, a transcription factor that regulates ARE-containing genes, on the synergistic cytotoxic effect of clofarabine and resveratrol was investigated in mesothelioma cells. The combination treatment showed a marked growth-inhibitory effect, which was accompanied by suppression of Nrf2 activation and decreased expression of heme oxygenase-1 (HO-1). While transient overexpression of Nrf2 conferred protection against the cytotoxicity caused by their combination, knockdown of Nrf2 expression using siRNA enhanced their cytotoxic effect. Pretreatment with Ly294002, a PI3K inhibitor, augmented the decrease in HO-1 level by their combination, whereas no obvious changes were observed in Nrf2 levels. Altogether, these results suggest that the synergistic cytotoxic effect of clofarabine and resveratrol was mediated, at least in part, through suppression of Nrf2 signaling.

• The Bulletin of The Korean Astronomical Society
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• v.35 no.1
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• pp.53.1-53.1
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• 2010

$Y^2$(Yonsei-Yale) Isochrones은 Yale의 항성 진화 계산을 이용한 정밀한 등연령곡선으로 구상성단의 연구에 널리 사용되고 있다. 이번 연구에서는 $Y^2$-Isochrones를 Kurucz 모형을 이용한 색변환을 통해서 SDSS로 널리 알려진 ugriz 필터 체계에 대해 적용하고 실제 관측 결과와 비교함으로써 타당성을 검증하고자 한다. 우선 ugriz 필터의 등연령곡선을 제공하는 BaSTI와 DSEP, Padova 모델간의 비교를 통해 $Y^2$-Isochorones이 MSTO에서 g-r값이 다른 모델에 비해 0.05정도 큼을 확인하였다. 또한 CFHT 3.6m 망원경의 가시광 카메라 MegaCam으로부터 얻은 중원소 함량이 낮은 다섯 개의 구상성단 M15, M30, M53, NGC 5053, NGC 5466에 대한 g, r, i 필터의 색등급도에 각각의 등연령곡선을 적용하여 모델에 따른 구상성단의 특성을 분석하였다. $Y^2$-isochrones를 이용한 (g-r, r) CMD의 분석 결과, BaSTI와 DSEP 모델에 비해 0.1~0.3만큼 거리지수가 크고, 성단의 나이는 1~3Gyr 정도 어리게 측정됨을 확인할 수 있었다. 더불어 SDSS 관측으로부터 얻어진 구상성단에 대한 색등급도와 비교 분석과정을 수행하여, 다른 망원경에서의 사용가능 여부를 확인하였다. 이 연구를 통하여 각 모델에 따른 등연령곡선의 차이를 확인하고, 현재 여러 망원경에서 사용되고, 앞으로 여러 대형망원경에서 사용될 ugriz 필터 체계에 $Y^2$-Isochrones를 적용할 수 있는 타당성을 제시하고자 한다.

• Molecules and Cells
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• v.38 no.5
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• pp.416-425
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• 2015

NF-E2-related factor 2 (Nrf2), a basic leucine zipper transcription factor, has recently received a great deal of attention as an important molecule that enhances antioxidative defenses and induces resistance to chemotherapy or radiotherapy. In this study, we investigated the apoptosis-inducing and Nrf2- upregulating effects of quercetin on malignant mesothelioma (MM) MSTO-211H and H2452 cells. Quercetin treatment inhibited cell growth and led to upregulation of Nrf2 at both the mRNA and protein levels without altering the ubiquitination and extending the half-life of the Nrf2 protein. Following treatment with quercetin, analyses of the nuclear level of Nrf2, Nrf2 antioxidant response element-binding assay, Nrf2 promoter-luc assay, and RT-PCR toward the Nrf2-regulated gene, heme oxygenase-1, demonstrated that the induced Nrf2 is transcriptionally active. Knockdown of Nrf2 expression with siRNA enhanced cytotoxicity due to the induction of apoptosis, as evidenced by an increase in the level of proapoptotic Bax, a decrease in the level of antiapoptotic Bcl-2 with enhanced cleavage of caspase-3 and PARP proteins, the appearance of a sub-$G_0/G_1$ peak in the flow cytometric assay, and increased percentage of apoptotic propensities in the annexin V binding assay. Effective reversal of apoptosis was observed following pretreatment with the pan-caspase inhibitor Z-VAD. Moreover, Nrf2 knockdown exhibited increased sensitivity to the anticancer drug, cisplatin, presumably by potentiating the oxidative stress induced by cisplatin. Collectively, our data demonstrate the importance of Nrf2 in cytoprotection, survival, and drug resistance with implications for the potential significance of targeting Nrf2 as a promising strategy for overcoming resistance to chemotherapeutics in MM.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.6
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• pp.493-502
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• 2020

Apigenin, a naturally occurring flavonoid, is known to exhibit significant anticancer activity. This study was designed to determine the effects of apigenin on two malignant mesothelioma cell lines, MSTO-211H and H2452, and to explore the underlying mechanism(s). Apigenin significantly inhibited cell viability with a concomitant increase in intracellular reactive oxygen species (ROS) and caused the loss of mitochondrial membrane potential (ΔΨm), and ATP depletion, resulting in apoptosis and necroptosis in monolayer cell culture. Apigenin upregulated DNA damage response proteins, including the DNA double strand break marker phospho (p)-histone H2A.X. and caused a transition delay at the G₂/M phase of cell cycle. Western blot analysis showed that apigenin treatment upregulated protein levels of cleaved caspase-3, cleaved PARP, p-MLKL, and p-RIP3 along with an increased Bax/Bcl-2 ratio. ATP supplementation restored cell viability and levels of DNA damage-, apoptosisand necroptosis-related proteins that apigenin caused. In addition, N-acetylcysteine reduced ROS production and improved ΔΨm loss and cell death that were caused by apigenin. In a 3D spheroid culture model, ROS-dependent necroptosis was found to be a mechanism involved in the anti-cancer activity of apigenin against malignant mesothelioma cells. Taken together, our findings suggest that apigenin can induce ROS-dependent necroptotic cell death due to ATP depletion through mitochondrial dysfunction. This study provides us a possible mechanism underlying why apigenin could be used as a therapeutic candidate for treating malignant mesothelioma.

• Journal of Life Science
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• v.26 no.7
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• pp.835-846
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• 2016

Chemo-resistance is the biggest issue of effective cancer therapy. ABCG2 is highly correlated with multi-drug resistance, and represent a typical phenotype of multiple cancer stem-like cells. Accumulating evidence recently reported that oncolytic viruses represent a new strategy for multiple aggressive cancers and drug resistant cancers including cancer stem cell-like cells and ABCG2 expressing cells. In this study, we generated an evolutionally engineered vaccinia virus, SLJ-496, for drug-resistant cancer therapy. We first showed that SLJ-496 treatment enhanced tumor affinity using cytopathic effect assay, plaque assay, as well as cell viability assay. Next, we clearly demonstrated that in vitro SLJ-496 treatment represents significant cytotoxic effect in multiple cancers including colorectal cancer cells (HT-29, HCT-116, HCT-8), gastric cancer cells (AGS, NCI-N87, MKN-28), Hepatocellular carcinoma cells (SNU-449, SNU-423, SNU-475, HepG2), as well as mesothelioma cell (NCI-H226, NCI-H28, MSTO-221h). Highly ABCG2 expressing HT-29 cells represent cancer stem like phenotype including stem cell marker expression, and self-renewal bioactivities. Interestingly, we demonstrated that in vitro treatment of SLJ-496 showed significant cytotoxicity effect, as well as viral replication capacity in ABCG2 overexpressing cell. In addition, we also demonstrated the cytotoxic effect of SLJ-496 in Adriamycin-resistant cell lines, SNU-620 and ADR-300. Taken together, these findings provide us a pivotal clue that cancer therapy using SLJ-496 vaccinia virus might be new therapeutic strategy to overcome ABCG2 expressing cancer stem-like cell and multiple chemo-resistance cancer cells.