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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
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Journal of Life Science
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Korean Society of Life Science
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Volume & Issues
Volume 26, Issue 8 - Aug 2016
Volume 26, Issue 7 - Jul 2016
Volume 26, Issue 6 - Jun 2016
Volume 26, Issue 5 - May 2016
Volume 26, Issue 4 - Apr 2016
Volume 26, Issue 3 - Mar 2016
Volume 26, Issue 2 - Feb 2016
Volume 26, Issue 1 - Jan 2016
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Identification and Functional Analysis of Pig β-1,4-N-Acetylglucosaminyltransferase A (MGAT4A)
Kim, Ji-Youn ; Hwang, Hwan-Jin ; Chung, Hak-Jae ; Park, Mi-Ryung ; Byun, Sung June ; Kim, Kyung-Woon ;
Journal of Life Science, volume 26, issue 3, 2016, Pages 275~281
DOI : 10.5352/JLS.2016.26.3.275
Glycan modification is important in pharmaceutical industry. Especially, sialic acid affects the bioactivity and stability of medicine. Milk of pig has been used as bioreactor to produce various pharmaceutical proteins. Therefore, it is necessary to modify the glycan chain in pig mammary grand. β-1,4-N-Acetylglucosaminyltransferase A (pMGAT4A) is one of the essential enzymes for increase of sialic acid content, but pig MGAT4A is unclear. In this study, the pMGAT4A was identified and characterized. The pMGAT4A has 1638 nucleotides encoding 535 amino acids and type II membrane topology, which is one of the common features in many glycosyltransferases. The gene was strongly expressed in liver and mammary gland, whereas was weakly expressed in small intestine, stomach and bladder. For functional test, HA-tagged MGAT4A was over-expressed in porcine kidney (PK-15) cell line. Forced expression of pMGAT4A gene was identified by qPCR, and we identified that pMGAT4A is located in Golgi complex by co- staining with HA antibody and BODIPY TR ceramide. In addition, we identified the increase of mannose-β-1,4-N-acetylglucosamine structure by ELISA and immunofluorescence using Datura stramonium agglutinin (DSA), which recognizes mannose-β-1,4-Nacetylglucosamine. Through the specific activity analysis, we showed that pMGAT4A modified bi-antennary to tri-antennary. This event affects sialic acid content. Therefore, we thought that over-expression of pMGAT4A will be necessary in pig mammary grand for improved medicine.
Wdpcp, a Protein that Regulates Planar Cell Polarity, Interacts with Multi‐PDZ Domain Protein 1 (MUPP1) through a PDZ Interaction
Jang, Won Hee ; Jeong, Young Joo ; Choi, Sun Hee ; Yea, Sung Su ; Lee, Won Hee ; Kim, Mooseong ; Kim, Sang-Jin ; Urm, Sang-Hwa ; Moon, Il Soo ; Seog, Dae-Hyun ;
Journal of Life Science, volume 26, issue 3, 2016, Pages 282~288
DOI : 10.5352/JLS.2016.26.3.282
Protein-protein interactions regulate the subcellular localization and function of receptors, enzymes, and cytoskeletal proteins. Proteins containing the postsynaptic density-95/disks large/zonula occludens-1 (PDZ) domain have potential to act as scaffolding proteins and play a pivotal role in various processes, such as synaptic plasticity, neural guidance, and development, as well as in the pathophysiology of many diseases. Multi-PDZ domain protein 1 (MUPP1), which has 13 PDZ domains, has a scaffolding function in the clustering of surface receptors, organization of signaling complexes, and coordination of cytoskeletal dynamics. However, the cellular function of MUPP1 has not been fully elucidated. In the present study, a yeast two-hybrid system was used to identify proteins that interacted with the N-terminal PDZ domain of MUPP1. The results revealed an interaction between MUPP1 and Wdpcp (formerly known as Fritz). Wdpcp was identified as a planar cell polarity (PCP) effector, which is known to have a role in collective cell migration and cilia formation. Wdpcp bound to the PDZ1 domain but not to other PDZ domains of MUPP1. The C-terminal end of Wdpcp was essential for the interaction with MUPP1 in the yeast two-hybrid assay. This interaction was further confirmed in a glutathione S-transferase (GST) pull-down assay. When coexpressed in HEK-293T cells, Wdpcp was coimmunoprecipitated with MUPP1. In addition, MUPP1 colocalized with Wdpcp at the same subcellular region in cells. Collectively, these results suggest that the MUPP1-Wdpcp interaction could modulate actin cytoskeleton dynamics and polarized cell migration.
In-vitro Antithrombosis Activity of Different Parts of Sorbus commixta from Ulleung Island
Kim, Mi-Sun ; Seong, Ha-Jung ; Sohn, Ho-Yong ;
Journal of Life Science, volume 26, issue 3, 2016, Pages 289~295
DOI : 10.5352/JLS.2016.26.3.289
Sorbus commixta, a flowering plant in the Rosaceae family, is native to Japan and Ulleung Island, Korea. This plant is also called maga-mok or mai-mok in Korea because the bud of the stem has a similar shape to the teeth of a horse. In this study, hot water extracts from different parts of S. commixta, such as leaf, stem, and immature and mature fruits, were prepared, and their antithrombosis and antioxidant activities were evaluated. The extraction yield and pH of stem extracts were 3.99% and 5.5, respectively. The stem extracts contained 89.2 mg/g of total polyphenols and 28.3 mg/g of total flavonoids. The hot water extracts prepared from the leaf, stem, immature, and mature fruit of S. commixta exhibited no hemolytic activity against human red blood cells, up to a concentration of 0.5 mg/ml. In an anticoagulation assay, the stem extracts showed strong extension in thrombin, prothrombin, and activated partial thromboplastin times, whereas the other extracts had no anticoagulation activity. In a platelet aggregation inhibitory activity assay, all the extracts tested had no inhibitory activity against human platelets. With regard to antioxidation activity, the stem extracts showed stronger radical scavenging activity and reducing power activity than the other extracts. The calculated RC
s, the concentration required for 50% radical scavenging activity, for DPPH anions, ABTS cations, and nitrite of the crude stem extracts were 119.7, 53.3, and 117.5 μg/ml, respectively, whereas they were 13.7, 5.2, and 14.9 μg/ml for DPPH anions, ABTS cations, and nitrite, respectively, for vitamin C. The results suggest that the stem extracts of S. commixta have strong potential for use as a novel resource for antithrombosis agents.
Purification of Antibacterial Peptide from the Skin of the Catfish Silurus asotus
Sohn, Hee-Young ; Go, Hye-Jin ; Park, Nam Gyu ;
Journal of Life Science, volume 26, issue 3, 2016, Pages 296~301
DOI : 10.5352/JLS.2016.26.3.296
An antibacterial peptide from skin extract of the catfish Silurus asotus was purified and characterized. The acidified skin extract was put through a Sep-Pak C18 solid phase extraction cartridge using a stepwise gradient and divided into flow-through (F.T.), 10% methanol-elute (RM10), 60% methanolelute (RM60), and 100% methanol-elute (RM100) fractions. RM10, RM60, and RM 100 showed antimicrobial activity against Escherichia coli D31. On the other hand, the F.T. fraction did not show antimicrobial activity. Among the various fractions, RM 60 had the highest activity. RM 60 was partially purified on a cation exchange column (CM52) by a stepwise gradient. The ammonium acetate (pH 5.15) 0.02 M – 0.8 M fraction showed antimicrobial activity. Then an antimicrobial peptide was purified using a 0.6M fraction with strong antibacterial activity through a series of five C18 reversed-phase HPLC columns. For the characterization of the purified peptide, the molecular weight and amino acid sequence were analyzed by MALDI-TOF MS and Edman degradation. The molecular weight of this peptide was about 4182.1 [M+H]
. The amino acid sequence of this peptide was partially determined as follows: PALXXKARREAKVKF. These findings suggest that this peptide plays a significant role in the innate defense system of catfish skin.
Effects of Oenanthe javanica and Allium tuberosum on Lipid Content in Rats Fed a High-fat·High-cholesterol Diet
Song, Won-Yeong ; Choi, Jeong-Hwa ;
Journal of Life Science, volume 26, issue 3, 2016, Pages 302~308
DOI : 10.5352/JLS.2016.26.3.302
This study was conducted to investigate the effects of Oenanthe javanica and Allium tuberosum powder on lipid metabolism in rats fed high fat·high cholesterol diet. Experimental rats were divided into five groups which were composed of normal diet group (N), high fat·high cholesterol diet group (HF), high fat·high cholesterol diet with 5% Oenanthe javanica powder diet group (OP), high fat·high cholesterol diet with 5% Allium tuberosum powder diet group (AP) and high fat·high cholesterol diet with 2.5% Oenanthe javanica and Allium tuberosum powder diet group (OAP). The serum TG content of the HF group was significantly increased compared to the N group, but that of the OAP group was significantly decreased. Serum HDL-cholesterol contents of the OAP group was significantly increased compared to the HF group. The serum total cholesterol, LDL-cholesterol and AI of the HF group were increased compared to the N group and especially the LDL-cholesterol of OP and OAP groups were significantly decreased compared to the HF group. The liver TG and total cholesterol contents of the HF group were significantly increased compared to the N group, while TG contents of the OAP group was significantly decreased compared to the HF group. Fecal total lipid and total cholesterol of OP, AP and OAP groups were significantly increased compared to the HF group. These results suggest that supplementation of Oenanthe javanica and Allium tuberosum may have a pronounced impact on markers of lipid metabolism in serum and liver of rats fed high fat·high cholesterol diets.
Effect of Oxytetracycline Injection an the Body of Paralichthys Olivaceus
Ko, Chang-Sik ; Kim, Dong-Hwi ; Park, So-Hyun ; Moon, Kyung-Mi ; Heo, Moon-Soo ;
Journal of Life Science, volume 26, issue 3, 2016, Pages 309~317
DOI : 10.5352/JLS.2016.26.3.309
Industrial advancements have resulted in food culture development, followed by increased seafood consumption and large-scale seafood farming, which has been accompanied by an increased prevalence of fish disease. The antibiotic oxytetracycline (OTC) is commonly used to prevent and treat bacterial diseases in fish. However, overuse of OTC had led to negative aspects. In view of this, we conducted a research with regard to aspects of remnants on olive flounder skin, liver, and muscle through dipping treatment and oral feeding of OTC and analyzed the results with bioassay and HPLC quantitative analyses. The dipping treatment was carried out once with 25 g/ton/hr of OTC, and the oral treatment with 62.5 mg/kg body weight/7 days. The results underwent a bioassay analysis. The dipping group reacted only on the skin right after dipping, while the oral feeding group responded on the skin for 77 days after feeding and on the muscle for 14 days. In the dipping group, the HPLC quantitative analysis revealed remnants in the skin on the 37th day and on the 13th day in the liver group. No remnants were found in the muscle, even immediately after dipping. In the oral feeding group, there was a high concentration (1.07 mg/kg) of remnant in the skin, even on the 77th day. 0.56 mg/kg in the liver, even a small amount, and no remnant in the muscle on the 42nd day. To sum up, the results suggest that it will not be harmful to our body to observe the OTC withdrawal period of 40 days with the muscle because OTC will hardly remain on it. When using olive flounder for sashimi, the skin and liver should not be used for broth, as the quantity of OTC residue is several times higher than that found in muscle. As previous studies reported that the concentration of remnants gradually decreased with heating, so it was likely to lessen, depending on the cooking temperature.
Enhancement of Anti-inflammatory Activity by Fermentation of Sargassum siliquanstrum
Lee, Sol-Ji ; Lee, Dong-Geun ; Kim, Mihyang ; Kong, Chang-Suk ; Yu, Ki-Hwan ; Kim, Yuck-Young ; Lee, Sang-Hyeon ;
Journal of Life Science, volume 26, issue 3, 2016, Pages 318~324
DOI : 10.5352/JLS.2016.26.3.318
This study was aimed to verify anti-inflammatory activity of fermented Sargassum siliquanstrum with lactic acid bacteria. Anti-inflammatory activities were compared by measuring the amount of nitric oxide (NO) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and suppressive effect on inducible nitric oxide synthase (iNOS) expression in stably transfected RAW 264.7 cells. Inhibitory activities of NO production and iNOS expression were measured after confirmation of NO radical scavenging activities. Fermentation increased NO radical scavenging activities from 7.6% to 15.2% compared to non-fermented condition, and fermentation with Lactobacillus sp. SH-1 was the most efficient. Fermentation without algal debris showed better NO radical scavenging activities than that with debris. Fermentation with Lactobacillus sp. SH-1 also showed the highest NO production inhibitory activity (64.1%) in LPS-stimulated RAW 264.7 cells. LPS-induced iNOS expression was diminished to 28.6, 35.6, 49.4 and 58.5 at 50, 100, 500 and 1,000 μg/ml, respectively, by fermentation with Lactobacillus sp. SH-1. According to MTT assay, fermented S. siliquanstrum did not influence the cell viability at all concentrations tested, meaning no or less cytotoxicity. These results suggest that S. siliquanstrum has NO radical scavenging activity and anti-inflammatory activity. Thus biological activities of S. siliquanstrum were upgraded by fermentation, which could be used for the development of functional foods.
Effect of Submerged Culture of Ceriporia lacerata Mycelium on Insulin Signaling Pathway in 3T3-L1 Cell
Shin, Eun Ji ; Kim, Ji-Eun ; Kim, Ji-Hye ; Park, Yong Man ; Yoon, Sung Kyoon ; Jang, Byeong-Churl ; Lee, Sam-Pin ; Kim, Byoung-Cheon ;
Journal of Life Science, volume 26, issue 3, 2016, Pages 325~330
DOI : 10.5352/JLS.2016.26.3.325
In this study, we evaluated the antidiabetic effect of submerged culture of Ceriporia lacerata mycelium (CL01) on glucose uptake and the expression of mRNA and protein of major signal markers of insulin signaling pathway in 3T3-L1 adipocytes. After 3T3-L1 adipocytes were pre-treated by CL01 (0, 2, 10 mg/ml) for 8 hours, followed with treatment of insulin, the glucose uptake levels significantly increased by more 55.1%, 94.4% than negative control respectively (p<0.01, 0.001) in a dose-dependent manner. However, in case of CL01 pre-treatment without insulin, the glucose uptake did not increase compared with insulin-treated 3T3-L1. Also we demonstrated that the protein expression levels of pIR β, pAkt, pPI3K and pAMPK and the mRNA expression levels of GLUT4 in adipocytes inducing insulin resistance increased in CL01-treated group compared with negative control. These results demonstrated that CL01 affected glucose metabolism and the protein and gene expression through insulin signaling pathway, and increased glucose uptake levels effectively. More than 90% of those who have suffered for type 2 diabetes are more likely to have from hyperinsulinemia, hypertension, obesity and etc. because of altered insulin signaling pathway. So, it is probably considered that intake of CL01 may treat type 2 diabetes by normalization of insulin signaling pathway, and it will provide useful evidences regarding a mechanism for cure of type 2 diabetes.
Effect of Fibroblast Growth Factor 23 on Osteoblastic Differentiation and Mineralization of D1 Mesenchymal Stem Cells
Park, Kyeong-Lok ;
Journal of Life Science, volume 26, issue 3, 2016, Pages 331~337
DOI : 10.5352/JLS.2016.26.3.331
Although fibroblast growth factor 23 (FGF23) is exclusively produced in osteoblasts and osteocytes, its main target is the kidney, where it decreases phosphate reabsorption by suppressing Na-phosphate cotransporters. Independently of its action on phosphate homeostasis, FGF23 also inhibits bone formation in vivo. In a calvarial osteoblastic cell model, FGF23 was shown to negatively affect extracellular matrix mineralization. This study investigated whether FGF23 had similar effects on osteoblast maturation, including differentiation and mineralization of bone marrow-derived mesenchymal stem cells (MSCs). D1 MSCs were cultured in an osteogenic medium containing β-glycerophosphate, ascorbic acid, and dexamethazone. Osteoblastic differentiation was evaluated by alkaline phosphatase (Alp) staining, and matrix mineralization was evaluated by alizarin red staining and calcium deposition. The expression of differentiation-stimulating genes Runx2, Alp, and osteocalcin and mineralization-inhibiting genes Enpp1 and Ank was analyzed using semiquantitative RT-PCR. Supraphysiological doses of FGF23 did not stimulate proliferation or osteoblastic differentiation of MSCs. Matrix mineralization 1, 2, and 3 weeks after the FGF23 treatment did not vary between control and FGF23 groups, although time-dependent enhancement of mineralization was obvious. Calcium deposition was also unchanged after the FGF23 treatment. mRNA expression levels of differentiation- and mineralization-related genes were also similar between the groups. Despite these negative findings, FGF23 signaling through FGF receptors seemed to function normally, with phosphorylation of the Erk protein more evident in the FGF23 group than in controls. These findings suggest that unlike calvarial osteoblasts, FGF23 is not likely to affect osteoblastic differentiation and mineralization of MSCs.
Antioxidant and Anti-inflammatory Effects of Extracts from the Flowers of Weigela subsessilis on RAW 264.7 Macrophages
Yoo, Yung Choon ; Lee, Gye Won ; Cho, Young Ho ;
Journal of Life Science, volume 26, issue 3, 2016, Pages 338~345
DOI : 10.5352/JLS.2016.26.3.338
This study investigated the antioxidant and anti-inflammatory activity of ethanol extract from the flowers of Weigela subsessilis (WS-E) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The total polyphenol and flavonoid content was 719.19±0.04 μg tannic acid equivalents/ml and 644.87±0.02 μg quercetin equivalents/ml, respectively. The antioxidant activities of WS-E were measured by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and superoxide anion radical scavenging activity. The antioxidant activities of WS-E increased markedly, in a dose-dependent manner. To screen for anti-inflammatory agents, the inhibitory effects of WS-E on the production of proinflammatory cytokines in the LPS-stimulated RAW 264.7 macrophages was examined. WS-E had no effect on cell viability at a concentration of 100 μg/ml. Nitric oxide (NO) and interleukin (IL)-6 production were inhibited in a dose-dependent manner (p<0.05). WS-E had no effect on the production of tumor necrosis factor (TNF)-α at a concentration of 0.16–20 μg/ml but induced TNF-α at a concentration of 100 μg/ml. Inducible nitric oxide synthase (iNOS) expression was also inhibited at lower concentrations (p<0.05). In addition, WS-E reduced the activation of nuclear factor (NF)-κB by inhibition of inhibitoy (I) κB phosphorylation in RAW 264.7 macrophages upon stimulation with LPS (100 ng/ml) for 24 h but not that of mitogen-activated protein kinase (MAPK). These results suggest that WS-E may be a useful antioxidant and anti-inflammatory agent in functional cosmetics.
Brain Wave Control Effect of Smart-wave via Docking into the Odorant-binding Protein
Kim, Dong-Chan ;
Journal of Life Science, volume 26, issue 3, 2016, Pages 346~352
DOI : 10.5352/JLS.2016.26.3.346
Aroma inhalation therapy has traditionally been used not only in alternative medicinal treatment but also in psychotherapy. In the first stage of the study, the in silico molecular binding affinity of the major ingredients of Smart-Wave (SW) on the active site of the odorant-binding protein (OBP) was compared with that of citrate anions. The binding affinity of the chemical mixture formula of the major ingredients of SW on the OBP was relatively higher than that of citrate anions. In addition, nasal inhalation of SW had a positive effect upon changes in brain waves. Eighteen healthy volunteers participated in the experiment. The study consisted of measurements of the brain’s meditation level recordings in the pre- and post-SW inhalation periods as compared with negative (EV) and positive (HB) control groups. After SW inhalation, all the subjects stated that they felt “fresher” and that the SW trial group had significantly changed the brain’s meditation in a positive way. SW inhalation also converted EV-induced unstable brain meditation wave patterns into more stable patterns. Collectively, the results of this empirical study strongly suggest that the SW mixture activates the OBP and controls the mental state by regulating brain waves. The results provide scientific evidence that the SW formula has potential as an effective mental-stress controller.
Crystal Structure of Thiolase from Clostridium butyricum
Kim, Eun-Jung ; Kim, Kyung-Jin ;
Journal of Life Science, volume 26, issue 3, 2016, Pages 353~358
DOI : 10.5352/JLS.2016.26.3.353
Thiolase is an enzyme that catalyzes condensation reactions between two acetyl-CoA molecules to produce acetoacetyl-CoA. As thiolase catalyzes is the first reaction in the production of n-butanol, knowledge of the molecular and regulatory mechanism of the enzyme is crucial for synthesizing high-value biofuel. Thiolase from Clostridium butyricum (CbTHL) was expressed, purified, and crystallized. X-ray diffraction data were collected from the crystals, and the 3-dimentional structure of the enzyme was determined at 2.0 Å. The overall structure of thiolase was similar to that of type II biosynthetic thiolases, such as thiolase from C. acetobutylicum (CaTHL). The superposition of this structure with that of CaTHL complexed with CoA revealed the residues that comprise the catalytic and substrate binding sites of CbTHL. The catalytic site of CbTHL contains three conserved residues, Cys88, His349, and Cys379, which may function as a covalent nucleophile, general base, and second nucleophile, respectively. For substrate binding, the way in which CbTHL stabilized the ADP moiety of CoA was unlike that of other thiolases, whereas the stabilization of β-mercaptoethyamine and pantothenic acid moieties of CoA was quite similar to that of other enzymes. The most interesting observation in the CbTHL structure was that the enzyme was regulated through redox-switch modulation, using a reversible disulfide bond.
Screening of Natural Product Libraries for the Extension of Cell Life-span through Immune System
Yoo, Bo-Kyung ; Kwon, Kisang ; Ko, Young Hwa ; Kim, Hong Geun ; Lee, Seokhyun ; Park, Kwan-Ho ; Choi, Ji-Young ; Kwon, O-Yu ;
Journal of Life Science, volume 26, issue 3, 2016, Pages 359~363
DOI : 10.5352/JLS.2016.26.3.359
We have screened four natural products against 640 single compounds, which shows more two folds gene expression for both endoplasmic reticulum aminopeptidase 1 (ERAP1) and FOXO-family transcription factor (FOXO1). The results were as follows. (±)-Car-3-ene-2,5-dione from Asarum sieboldii Miq. is C
molecular formula and the 164 kDa molecular weight. Cinobufagin from Bufonis Venennum is C
molecular formula and 442 kDa molecular weight. So far reported main biological function is Na
-ATPase inhibition. Corilagin from Euphorbia pekinensis is C
molecular formula and 634 kDa molecular weight. Carbonic anhydrase inhibition is well known its biological function. Corydaline from Corydalis turtschaninovii is C
molecular formula and 369 kDa molecular weight. The main biological function is acetylcholinesterase inhibition. In the short future, four types of natural products will be used in longevity experiments with insects. The results may give one of the clues for studying new drug development candidates of the longevity.
Structure and Biological Function of Plant CRL4, and Its Involvement in Plant Cellular Events
Lee, Jae-Hoon ;
Journal of Life Science, volume 26, issue 3, 2016, Pages 364~375
DOI : 10.5352/JLS.2016.26.3.364
Post-translational modification is an efficient process to rapidly transduce external stimulus into cellular response. Ubiquitination is a typical post-translational modification which is a highly conserved process in eukaryotes. UPS (Ubiquitin/Proteasome System) mediated by the ubiquitination is to target diverse cellular proteins for degradation. Among E3 ubiquitin ligases that function as the key determinant for substrate recognition, CRL (cullin–RING E3 ubiquitin ligase) is the largest family and forms the complex composed of cullin, RBX1, adaptor and substrate receptor. Although CRL1, also known as SCF complex, has been widely researched for its biological role, the functional studies of CRL4 have been relatively elusive. In Arabidopsis, there are 119 substrate receptors named DCAF (DDB1 CUL4 Associated Factor) proteins for CRL4 and a fraction of DCAF proteins have been identified for their potential functions so far. In this paper, current understanding on structure and biological roles of plant CRL4 complexes in a diverse of cellular events is reviewed, especially focusing on CRL4 substrate receptors. Moreover, the regulatory mechanism of CRL4’s activity is also introduced. These studies will be helpful to further understand the signal transduction pathways in which such CRL4 complexes are involved and give a clue to establish the action network of entire CRL4 complexes in plants.
Microtubule-damaging Chemotherapeutic Agent-mediated Mitotic Arrest and Apoptosis Induction in Tumor Cells
Jun, Do Youn ; Kim, Young Ho ;
Journal of Life Science, volume 26, issue 3, 2016, Pages 376~386
DOI : 10.5352/JLS.2016.26.3.376
Apoptosis induction has been proposed as an efficient mechanism by which malignant tumor cells can be removed following chemotherapy. The intrinsic mitochondria-dependent apoptotic pathway is frequently implicated in chemotherapy-induced tumor cell apoptosis. Since DNA-damaging agent (DDA)-induced apoptosis is mainly regulated by the tumor suppressor protein p53, and since more than half of clinical cancers possess inactive p53 mutants, microtubule-damaging agents (MDAs), of which apoptotic effect is mainly exerted via p53-independent routes, can be promising choice for cancer chemotherapy. Recently, we found that the apoptotic signaling pathway induced by MDAs (nocodazole, 17α-estradiol, or 2-methoxyestradiol) commonly proceeded through mitotic spindle defect-mediated prometaphase arrest, prolonged Cdk1 activation, and subsequent phosphorylation of Bcl-2, Mcl-1, and Bim in human acute leukemia Jurkat T cells. These microtubule damage-mediated alterations could render the cellular context susceptible to the onset of mitochondria-dependent apoptosis by triggering Bak activation, Δψm loss, and resultant caspase cascade activation. In contrast, when the MDA-induced Bak activation was inhibited by overexpression of anti-apoptotic Bcl-2 family proteins (Bcl-2 or Bcl-xL), the cells in prometaphase arrest failed to induce apoptosis, and instead underwent mitotic slippage and endoreduplication cycle, leading to formation of populations with 8N and 16N DNA content. These data indicate that cellular apoptogenic mechanism is critical for preventing polyploid formation following MDA treatment. Since the formation of polyploid cells, which are genetically unstable, may cause acquisition of therapy resistance and disease relapse, there is a growing interest in developing new combination chemotherapies to prevent polyploidization in tumors after MDA treatment.