• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.6
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• pp.1664-1671
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• 2006

Cisplatin is a anti-neoplastic agent which is commonly used for the treatment of solid tumor. Cisplatin activates multiple signal transduction pathways involved in the stress-induced apoptosis in a variety of cell types. Cytotoxicity of cisplatin was detected in rat mesangial cells and the value of $IC_{50}$ is about 20 ${\mu}M$. The treatment of cisplatin to rat mesangial cells showed the apoptotic bodies and DNA fragmentation. The activation of caspase-3, -8, and -9 and proteolytic cleavage of PARP were observed in the rat mesangial cells treated time-dependently with cisplatin. The activation of ERK, p38 and JNK was also observed in the apoptosis induced by cisplatin in rat mesangial cells. The ethanol extract of Bojungbangam-tang (EBJT), a new hergal prescription composed of nine crude drugs, inhibited cisplatin-induced apoptosis in rat mesangial cells. EBJT reduced sub-G1 peak (apoptotic peak) in cisplatin-treated rat mesangial cells. The cisplatin-induced ERK and JNK activation in rat mesangial cells were blocked by EBJT, but EBJT had no effect on p38 activation. Taken together, these results con suggest that EBJT prevents cisplatin-induced apoptotic cell death in rat mesangial cells through inhibition of ERK and JNK activation.

• Journal of Physiology & Pathology in Korean Medicine
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• v.35 no.4
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• pp.117-123
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• 2021

Gefitinib, a first generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI), provides obvious clinical benefit in patients with EGFR-mutant non-small cell lung cancer (NSCLC). However, patients ultimately develop gefitinib resistance which mainly caused by EGFR T790M secondary mutation. In the current study, we investigated whether the root extract of Scutellaria baicalensis (SB) overcomes gefitinib resistance. Gefitinib-resistant H1975 human NSCLC cells (EGFR L858R/T790M double mutant) were treated with gefitinib and/or ethanol extract of SB (ESB) to evaluate the effect of ESB on the gefitinib sensitivity. The cell viability was measured by MTT assay and trypan blue exclusion assay. The colony-forming ability was evaluated by anchorage-dependent colony formation assay. Combined treatment with gefitinib and ESB markedly decreased the cell viability and colony formation than single treatment with gefitinib or ESB in H1975 cells. In addition, cells treated with both gefitinib and ESB exhibited a significant increase of sub-G1 DNA content which indicates apoptotic cells compared with those treated with gefitinib or ESB alone. As a molecular mechanism, combined treatment with gefitinib and ESB strongly downregulated the phosphorylation of ERK and JNK than single treatment with gefitinib or ESB. Taken together, our results demonstrate that ESB sensitizes H1975 cells to gefitinib treatment. We cautiously propose that ESB can be used in combination with gefitinib for the advanced NSCLC patients with acquired resistance to EGFR TKIs.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.465-469
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• 2015

Background: Orostachys japonicus A. Berger (A. Berger) is commonly used as a folk remedy for cancer therapy. However, the mechanisms of its anti-cancer activity are poorly investigated in human cancer cells. In this study, we investigated whether flavonoids extracted from Orostachys japonicus A. Berger (FEOJ) might have anticancer effects in human leukemia cells, focusing on cell death mechanisms. Materials and Methods: U937 human leukemic cancer cells were used. Results: FEOJ induced apoptosis in a dose-dependent manner in human U937 cancer cells. Flow cytometry revealed significant accumulation of cells with sub-G1 DNA content at the concentrations of $200{\mu}g/mL$ and $400{\mu}g/mL$. FEOJ-induced apoptosis was caspase-dependent through loss of mitochondrial membrane potential (MMP, ${\Delta}{\Psi}m$) in human U937 cancer cells, which might be associated with suppression of Bcl-2 and XIAP proteins. FEOJ induced the p38 MAPK signaling pathway, playing at least in part an important role in FEOJ-induced apoptosis. Conclusions: This study suggested that FEOJ may induce caspase-dependent apoptosis in human leukemic cells by regulating MMP (${\Delta}{\Psi}m$) through suppressing Bcl-2 and X-IAP. In addition, the results indicated that upstream p38 MAPK signaling regulates the apoptotic effect of FEOJ. This study provides evidence that FEOJ might have anti-cancer potential for human leukemic cells.

• Korean Journal of Medicinal Crop Science
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• v.8 no.2
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• pp.102-108
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• 2000

Morphological characteristics of nine Epimedium spp was analyzed on the basis of six morphological characters. To analyse the genetic relationship among Epimedium spp., polymerase chain reaction (PCR) was performed with total genomic DNA of 17 Epimedium spp. by using random 8 primers. The genetic diversity and genetic distance among nine Korean collections, seven Japanese and one China collection were used to generate a dendrogram showing phylogenie relationship. Seventeen Epimedium spp were classified into two groups of group I and II, since they were divided into two major groups at the similarity coefficients value of 0.65. In addition, one of the two group, group I was divided into three sub-groups including Epimedium koreanum, Chul-won collections 1, 2, and 3, Yanggu, Hongchon, Hwachun, Chunchon, China, Maehwa (Japanese), E. diphyllum and E. violaceum (Japanese), while group II included Chulwon collection 4 and 5 and Japanese collection. The samples collected at Chulwon district showed close similarity with Japanese collection. Similarity indexes between collection and genetic relationship were related at the levels ranging from 0.6 to 0.9.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.6039-6046
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• 2015

Aims: To investigate effect of metallic nanoparticles, silver (AgNPs) and gold nanoparticles (AuNPs) as antitumor treatment in vitro against human breast cancer cells (MCF-7) and their associated mechanisms. This could provide new class of engineered nanoparticles with desired physicochemical properties and may present newer approaches for therapeutic modalities to breast cancer in women. Materials and Methods: A human breast cancer cell line (MCF-7) was used as a model of cells. Metallic nanoparticles were characterized using UV-visible spectra and transmission electron microscopy (TEM). Cytotoxic effects of metallic nanoparticles on MCF-7 cells were followed by colorimetric SRB cell viability assays, microscopy, and cellular uptake. Nature of cell death was further investigated by DNA analysis and flow cytometry. Results: Treatment of MCF-7 with different concentrations of 5-10nm diameter of AgNPs inhibited cell viability in a dose-dependent manner, with IC50 value of $6.28{\mu}M$, whereas treatment of MCF-7 with different concentrations of 13-15nm diameter of AuNPs inhibited cell viability in a dose-dependent manner, with IC50 value of $14.48{\mu}M$. Treatment of cells with a IC50 concentration of AgNPs generated progressive accumulation of cells in the S phase of the cell cycle and prevented entry into the M phase. The treatment of cells with IC50 concentrations of AuNPs similarly generated progressive accumulation of cells in sub-G1 and S phase, and inhibited the entrance of cells into the M phase of the cell cycle. DNA fragmentation, as demonstrated by electrophoresis, indicated induction of apoptosis. Conclusions: Our engineered silver nanoparticles effectively inhibit the proliferation of human breast carcinoma cell line MCF-7 in vitro at high concentration ($1000{\mu}M$) through apoptotic mechanisms, and may be a beneficial agent against human carcinoma but further detailed study is still needed.

• Molecules and Cells
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• v.24 no.1
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• pp.95-104
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• 2007

The mechanism of acacetin-induced apoptosis of human breast cancer MCF-7 cells was investigated. Acacetin caused 50% growth inhibition ($IC_{50}$) of MCF-7 cells at $26.4{\pm}0.7{\mu}M$ over 24 h in the MTT assay. Apoptosis was characterized by DNA fragmentation and an increase of sub-G1 cells and involved activation of caspase-7 and PARP (poly-ADP-ribose polymerase). Maximum caspase 7 activity was observed with $100{\mu}M$ acacetin for 24 h. Caspase 8 and 9 activation cascades mediated the activation of caspase 7. Acacetin caused a reduction of Bcl-2 expression leading to an increase of the Bax:Bcl-2 ratio. It also caused a loss of mitochondrial membrane potential that induced release of cytochrome c and apoptosis inducing factor (AIF) into the cytoplasm, enhancing ROS generation and subsequently resulting in apoptosis. Pretreatment of cells with N-acetylcysteine (NAC) reduced ROS generation and cell growth inhibition, and pretreatment with NAC or a caspase 8 inhibitor (Z-IETD-FMK) inhibited the acacetin-induced loss of mitochondrial membrane potential and release of cytochrome c and AIF. Stress-activated protein kinase/c-Jun $NH_4$-terminal kinase 1/2 (SAPK/JNK1/2) and c-Jun were activated by acacetin but extracellular-regulated kinase 1/2 (Erk1/2) nor p38 mitogen-activated protein kinase (MAPK) were not. Our results show that acacetin-induced apoptosis of MCF-7 cells is mediated by caspase activation cascades, ROS generation, mitochondria-mediated cell death signaling and the SAPK/JNK1/2-c-Jun signaling pathway, activated by acacetin-induced ROS generation.

• The Journal of Internal Korean Medicine
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• v.29 no.1
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• pp.130-148
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• 2008

Objective : This study was designed to investigate the effect of the water extract of Gamisamgibopae-tang(GMSGBPT), an oriental herbal formulation, on the growth of NCI-H460 and A549 human non-small-cell lung cancer cell lines. Methods : Cytotoxicity and cell morphology were evaluated by MTT assay and inverted microscope, respectively. Apoptosis was detected using agarose gel electrophoresis and flow cytometer. The expression levels of mRNAs and proteins of target genes were determined by RT-PCR and western blot analyses, respectively Result and Conclusion : We found that exposure of A549 cells to GMSGBPT resulted in the growth inhibition in a dose-dependent manner as measured by MTT assay, but GMSGBPTdid not affect the growth of NCI-H460 cells. The anti-proliferative effect of GMSGBPT treatment in A549 cells was associated with morphological changes, formation of apoptotic bodies and DNA fragmentation, and flow cytometry analysis confirmed that GMSGBPT treatment increased the populations of apoptotic-sub G1 phase. Growth inhibition and apoptotic cell death by GMSGBPT were connected with a up-regulation of cyclin-dependent kinase inhibitor p21 (WAF1/CIP1) mRNA and protein in a tumor suppressor p53-independent fashion. However GMSGBPT treatment did not affect other growth regulation-related genes such as early growth response-1 (Egr-1), nonsteroidal anti-inflammatory drug (NSAID)-activated gene-1 (NAG-1), inducible nitric oxide synthase (iNOS), cyclooxygenases (COXs), telomere-regulatory factors in A549 orNCI-H460 cells. Taken together, these findings partially provide novel insights into the possible molecular mechanism of the anti-cancer activity of GMSGBPT.

• BMB Reports
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• v.38 no.6
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• pp.755-762
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• 2005

Epstein-Barr virus (EBV) infects more than 90% of the world's population and has a potential oncogenic nature. A histone deacetylase (HDAC) inhibitor, trichostatin A (TSA), has shown potential ability in cancer chemoprevention and treatment, but its effect on EBV-infected Akata cells has not been examined. This study investigated the effect of TSA on the proliferation and apoptosis of the cells. TSA inhibited cell growth and induced cytotoxicity in the EBV infected Akata cells. TSA treatment sensitively induced apoptosis in the cell, which was demonstrated by the increased number of positively stained cells in the TUNEL assay, the migration of many cells to the sub-$G_0/G_1$ phase in flow cytometric analysis, and the ladder formation of genomic DNA. Western blot analysis showed that caspase-dependent pathways are involved in the TSA-induced apoptosis of EBV-infected Akata cells. Overall, this study shows that EBV-infected B lymphomas are quite sensitive to TSA-provoked apoptosis.

• Journal of Mushroom
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• v.14 no.4
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• pp.211-214
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• 2016

Geoni, a new variety of Auricularia polytricha, was bred in JARES(Jeollanamdo Agricultural Research and Extension Services) in 2012. Geoni was selected through the monospore hybridization with JNM21008 and JNM21014 in 2010. Based on a performance test conducted from 2011 to 2012, the Geoni was selected from a line showing an excellent light brown pileus and strong pest resistance. Geoni has a favorable chewiness, light brown and smooth pileus. In addition, Geoni was rich in dietary fiber. MCM(mushroom complete medium), Malt and PDA(Potato Dextrose Agar) mediums were suitable for cultivating the Geoni. The number of effective stipes was 39 ea/0.9 kg and minor axis and major axis of pileus were 6.9 cm and 8.7 cm respectively. The yield of Geoni was 291 g/0.9 kg in plastic bag. Geoni was required 40~54 days for culture at $20^{\circ}C$ and 24days for the primordia and growth period, which is longer than that of the control(Pung-un). Somatic incompatibility was formed between parental strains and Geoni. Analysis of the genetic diversity of the new variety "Geoni"revealed a different profile from the parental strains when RAPD(random Amplified Polymorphic DNA) primers were used.

• Journal of Life Science
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• v.18 no.1
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• pp.120-128
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• 2008

The death ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/ Apo1L is a cytokine that activates apoptosis through cell surface death receptors. TRAIL has sparked growing interest in oncology due to its reported ability to selectively trigger cancer cell death. Euphorbiae humifusae Wind has been used in traditional Oriental medicine as a folk remedy used for the treatment of cancer. However, the mechanism responsible for the anticancer effects of E. humifusae not clearly understood. Here, we show that treatment with subtoxic doses of water extract of E. humifusae (WEEH) in combination with TRAIL induces apoptosis in TRAIL-resistant human gastric carcinoma AGS cells. Combined treatment with WEEH and TRAIL induced chromatin condensation and sub-G1 phase DNA content. These indicators of apoptosis were correlated with the induction of caspase activity that resulted in the cleavage of poly (ADP-ribose) polymerase. Combined treatment also triggered the loss of mitochondrial membrane potential. Furthermore, co-treatment with WEEH and TRAIL down-regulated the protein levels of the anti-apoptotic proteins such as Bcl-2, Bcl-xL, XIAP and cIAP-1. Although more study will be needed to examine the detailed mechanisms, this combined treatment may offer an attractive strategy for safely treating gastric adenocarcinomas and the results provide important new insights into the possible molecular mechanisms of the anticancer activity of E. humifusae.