• Title/Summary/Keyword: Bak activation

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Activation of JNK/p38 Pathway is Responsible for α-Methyl-n-butylshikonin Induced Mitochondria-Dependent Apoptosis in SW620 Human Colorectal Cancer Cells

  • Wang, Hai-Bing;Ma, Xiao-Qiong
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.15
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    • pp.6321-6326
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    • 2014
  • ${\alpha}$-Methyl-n-butylshikonin (MBS), one of the active components in the root extracts of Lithospermum erythrorhizon, posses antitumor activity. In this study, we assess the molecular mechanisms of MBS in causing apoptosis of SW620 cells. MBS reduced the cell viability of SW620 cells in a dose-and time-dependent manner and induced cell apoptosis. Treatment of SW620 cells with MBS down-regulated the expression of Bcl-2 and up-regulated the expression of Bak and caused the loss of mitochondrial membrane potential. Additionally, MBS treatment led to activation of caspase-9, caspase-8 and caspase-3, and cleavage of PARP, which was abolished by pretreatment with the pan-caspase inhibitor Z-VAD-FMK. MBS also induced significant elevation in the phosphorylation of JNK and p38. Pretreatment of SW620 cells with specific inhibitors of JNK (SP600125) and p38 (SB203580) abrogated MBS-induced apoptosis. Our results demonstrated that MBS inhibited growth of colorectal cancer SW620 cells by inducing JNK and p38 signaling pathway, and provided a clue for preclinical and clinical evaluation of MBS for colorectal cancer therapy.

Study on the Isomeric Ratio by Thermal Neutron Activation

  • Bak, Hae-Ill
    • Nuclear Engineering and Technology
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    • v.6 no.2
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    • pp.89-96
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    • 1974
  • The cross-section ratios of the nuclear isomeric pairs $^{80}$ B $r^{m, g}$, sup 81/S $e^{m, g}$, $^{104}$ R $h^{m, g}$, $^{116}$ I $n^{m, g}$ and $^{134}$ C $s^{m, g}$ through the radiative thermal neutron capture process have been studied. The experimental values of these ratios obtained by the activation method have been compared with the calculated ones deduced from the modified Huizenga-Vandenbosch method. Agreement between these values within 30% could be attained by controlling the spin cut-off parameter and gamma-ray multiplicity.

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Microtubule-damaging Chemotherapeutic Agent-mediated Mitotic Arrest and Apoptosis Induction in Tumor Cells (미세소관-손상 항암제 처리에 의한 세포주기의 정지 및 에폽토시스 유도)

  • Jun, Do Youn;Kim, Young Ho
    • Journal of Life Science
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    • v.26 no.3
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    • pp.376-386
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    • 2016
  • 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.

A Single Comparator Method Using Reactor Neutron and Its Errors (원자로 중성자를 이용한 단일 비교체법과 오차)

  • Nak Bae Kim;Keung Shik Park;Hae-Ill Bak
    • Nuclear Engineering and Technology
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    • v.18 no.2
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    • pp.85-91
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    • 1986
  • A single comparator method with its accuracy has been studied for determining multielement by reactor neutron activation analysis. Spectral index at the irradiation position of each sample was determined using two flux monitors of Au and Co, one of which was used as a single comparator. The uncertainties of nuclear data related to the method were investigated for 18 elements and the error of the analytical result due to the uncertainties of nuclear data related is found to be less than 6%. The analytical results of 4 USGS reference samples agree well within 15% deviation with the results evaluated by USGS.

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MODULATION OF THE ACTIVITY OF PRO-INFLAMMATORY ENZYMES, COX-2 AND iNOS, BY CHRYSIN DERIVATIVES

  • Cho, Hee-Yeong;Yun, Cheol-Won;Kong, Jae-Yang;Kim, Kyoung-Soon;Park, You-Mie;Lee, Sang-Hyun;Kim, Bak-Kwang
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.286.1-286.1
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    • 2003
  • Chrysin, a natural flavone compound contained in plants. has anti-inflammatory activity. Its anti-inflammatory effect has been previously explained in part by the suppression of promoter activities of inducible pro-inflammatory enzymes (cyclooxygenase-2 (COX-2) and inducible nitrogen synthase (iNOS)). Nitrate production triggered by the activation of lipopolysaccharides (LPS) was most highly suppressed by the treatment of chrysin, follwed by 5-hydroxy-7-methoxyflavone (Ch-2), 5,7-diacetylflavone (Ch-4) in cultured Raw 264.7 cells. (omitted)

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The Effects of Performing a One-legged Bridge with Hip Abduction and Unstable Surface on Trunk and Gluteal Muscle Activation in Healthy Adults

  • Bak, Jong-Woo;Cho, Min-Kwon;Chung, Yi-Jung
    • The Journal of Korean Physical Therapy
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    • v.28 no.3
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    • pp.205-211
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    • 2016
  • Purpose: This study investigated the influence of muscle activity of the trunk and lower limb during a bridge exercise using a unstable surface and during one-legged bridge hip abduction in healthy adults. Methods: Nineteen healthy participated in this study (12 males and 7 females, aged $29.0{\pm}5.0$). The participants were instructed to perform the bridge exercises under six different conditions. Trunk and lower limb muscle activation, such as the erector spinae (ES), gluteus maximus (GM), external oblique (EO), and internal oblique (IO), was measured using surface electromyography. The six different bridge exercise conditions were conducted randomly. Data analysis was performed by using the mean scores after three trials of each condition. Results: On the ipsilateral side, muscle activity of the IO, EO, and ES during the hip abduction condition (Single-legged hip abduction bridge, Bridge with use of a ball and single-leg hip abduction, Bridge with use of a sling and single-leg hip abduction) was significantly higher than those during Unstable surface (Bridge with use of a ball, Bridge with use of a sling) and General bridging exercise (p<0.05). In the contralateral side, activities of the GM and EO during Single-legged hip abduction bridge, Bridge with use of a ball and single-leg hip abduction and Bridge with use of a sling and single-leg hip abduction was significantly higher than that during Bridge with use of a ball, Bridge with use of a sling and General bridging exercise (p<0.05). Conclusion: This study demonstrated that performing a bridge exercise with use of a sling and single-leg hip abduction had an effect on trunk and gluteal muscle activation. The findings of this study suggest that this training method can be clinically effective for unilateral training and for patients with hemiplegia.

Extract of Broussometia kazinoki Induces Apoptosis Through the Mitochondria/Caspase Pathway in A549 Lung Cancer Cells (A549세포에서 닥나무 추출물의 미토콘드리아/Caspase 경로를 통한 Apoptosis 유도작용)

  • Kim, Tae Hyeon;Kim, Dan Hee;Mun, Yeun Ja;Lim, Kyu Sang;Woo, Won Hong
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.30 no.3
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    • pp.150-156
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    • 2016
  • Extract of Broussometia kazinoki Rhizodermatis has been traditionally used for geopoong, diuresis, hwalhyeol. In the present study, the apoptotic effect of methanol extract of Broussometia kazinoki (MBK) were investigated. Cell viability of A549 cells was measured by MTT assay. Apoptosis-related protein and MAPK protein levels were measured by Western blot. Chromatin condensation of A549 cells was stained with DAPI. MBK inhibited cell proliferation of A549 cell. Based on DAPI staining, MBK-treated cells manifested nuclear shrinkage, condensation and fragmentation. Treatment of A549 cells with MBK resulted in activation of the caspase-3, -8, -9 and cleavage of poly ADP-ribose polymerase (PARP). In the upstream, MBK increased the expressions Bax and Bak, decreased the expression of Bcl-2, and augmented the Bax/Bcl-2 ratio. MBK-induced apoptosis was accompanied by sustained phosphorylation of JNK, p38 MAPK and apoptosis signal-regulating kinase (ASK)-1. These results suggest that MBK induced apoptosis in A549 cells through Bcl-2 family protein-mediated mitochondria/caspase-3 dependent pathway. In addition, MBK increased the activation of ASK-1, which are critical upsteam signals for JNK/p38 MAPK activation in A549 cancer cells.

Study of Sophorae Radix on $H_2O_2$-mediated Apoptosis and Total Protein Expression Pattern in Vascular Smooth Muscle Cells (고삼이 $H_2O_2$에 의한 대동맥 평활근세포 고사 및 전체 단백질 발현에 미치는 영향)

  • Jeon In Cheol;Jeong Jae Eun;Son In Hwan;Lee Ju Seok;Jeong Seung Won;Jang Jae Ho;Lee Seon U;Lee In;Moon Byun Soon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.18 no.6
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    • pp.1652-1660
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    • 2004
  • Apoptosis of vascular smooth muscle cells(VSMCs) is essential in atherogenesis, being a factor that modulates its early progression rather than a terminal event in the course of the disease. Various stimuli, including oxide lipoproteins, altered hemodynamic stress and free radical, can induced VSMCs apoptosis in vitro. The protective effects of Sophorae Radix (SR) on apoptotic cell death induced by H₂O₂ were investigated in VSMCs. The viability of VSMCs was markedly decreased by H₂O₂. Sophorae Radix protected the H202-induced apoptotic death of VSMCs, which was characterized as nuclear fragmentation and increase of sub-G0/G1 fraction .. Sophorae Radix decreased the activation of caspase-3 like protease induced by H₂O₂ and recovered control level from H202-induced PARP, Bak, Bcl-XL and mitochondrial membrane potential. These results suggest that Sophorae Radix protected VSMCs apoptotic death induced by H₂O₂ via inactivation of caspase-3 and modulation of mitochondrial function. Also, the expression profile of proteins by using two-dimensional (2-D) gel electrophoresis was screened. Future investigations will need to explore the use of an anti atherosclerotic therapy of Sophorae Radix, which relies on inhibition of the proapoptotic activation of the vascular smooth muscle cells.

Extract of Alnus japonica Induces Apoptosis of Human Colon Adenocarcinoma Cells through the Mitochondria/Caspase Pathway (대장암세포주에서 적양 추출물의 미토콘드리아/Caspases 경로를 통한 Apoptosis 유도 작용)

  • Jeon, Byoung-Kook;Baik, Soon-Ki;Woo, Won-Hong;Mun, Yeun-Ja
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.26 no.2
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    • pp.199-205
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    • 2012
  • An extract of Alnus japonica (Betulaceae) cortex has been traditionally used for purifying blood, and curing feces containing blood, enteritis, diarrhea, alcoholism and cut wounds. In the present study, we demonstrated that the ethanol extract of Alnus japonica (EAJ) exhibited significantly cytotoxicity in human colon adenocarcinoma HT-29 cells. The results showed that the induction of apoptosis in HT-29 cells by EAJ was characterized by chromatin condensation and activation of caspase-3. EAJ-induced activation of caspase-9 and -3 caused the cleavage of poly ADP-ribose polymerase (PARP) and the release of cytochrome c. The expressions of Bcl-2 and Bid were reduced by EAJ in HT-29 cells, whereas pro-apoptotic protein Bak was increased in the cells. EAJ-induced, dose-dependent induction of apoptosis was accompanied by sustained phosphorylation of MAP kinases (JNK and p38 MAPK), ASK1, and p53. NAC administration, a scavenger of ROS, reversed EAJ-induced cell death. In conclusion, these results indicated that EAJ can cause apoptosis through a ROS-mitochondria-caspases-dependent pathway in human HT-29 cells.

Heme oxygenase-1 (HO-1)/carbon monoxide (CO) axis suppresses RANKL-induced osteoclastic differentiation by inhibiting redox-sensitive NF-κB activation

  • Bak, Sun-Uk;Kim, Suji;Hwang, Hae-Jun;Yun, Jung-A;Kim, Wan-Sung;Won, Moo-Ho;Kim, Ji-Yoon;Ha, Kwon-Soo;Kwon, Young-Guen;Kim, Young-Myeong
    • BMB Reports
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    • v.50 no.2
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    • pp.103-108
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    • 2017
  • Heme oxygenase (HO-1) catalyzes heme to carbon monoxide (CO), biliverdin/bilirubin, and iron and is known to prevent the pathogenesis of several human diseases. We assessed the beneficial effect of heme degradation products on osteoclastogenesis induced by receptor activator of NF-${\kappa}B$ ligand (RANKL). Treatment of RAW264.7 cells with CORM-2 (a CO donor) and bilirubin, but not with iron, decreased RANKL-induced osteoclastogenesis, with CORM-2 having a more potent anti-osteogenic effect. CORM-2 also inhibited RANKL-induced osteoclastogenesis and osteoclastic resorption activity in marrow-derived macrophages. Treatment with hemin, a HO-1 inducer, strongly inhibited RANKL-induced osteoclastogenesis in wild-type macrophages, but was ineffective in $HO-1^{+/-}$ cells. CORM-2 reduced RANKL-induced NFATc1 expression by inhibiting IKK-dependent NF-${\kappa}B$ activation and reactive oxygen species production. These results suggest that CO potently inhibits RANKL-induced osteoclastogenesis by inhibiting redox-sensitive NF-${\kappa}B$-mediated NFATc1 expression. Our findings indicate that HO-1/CO can act as an anti-resorption agent and reduce bone loss by blocking osteoclast differentiation.