• Title, Summary, Keyword: PKM2

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Induction of Apoptosis in Human Leukemic Cell Lines by Diallyl Disulfide via Modulation of EGFR/ERK/PKM2 Signaling Pathways

  • Luo, Nian;Zhao, Lv-Cui;Shi, Qing-Qiang;Feng, Zi-Qiang;Chen, Di-Long;Li, Jing
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.8
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    • pp.3509-3515
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    • 2015
  • Background: Diallyl disulfide (DADS) may exert potent anticancer action both in vitro and in vivo. Although its effects on cancer are significant, the underlying mechanisms remain unknown. In this study, we sought to elucidate possible links between DADS and pyruvate kinase (PKM2). Materials and Methods: $KG1{\alpha}$, a leukemia cell line highly expressing PKM2 was used with a cell counting kit (CCK)-8 and flow cytometry (FCM) to investigate the effects of DADS. Relationships between PKM2 and DADS associated with phosphorylation of EGFR, ERK1/2 and MEK, were assessed by western blot analysis. Results: In $KG1{\alpha}$ cells highly expressing PKM2, we found that DADS could affect proliferation, apoptosis and EGFR/ERK/PKM2 signaling pathways, abrogating EGF-induced nuclear accumulation of PKM2. Conclusions: These results suggested that DADS suppressed the proliferation of $KG1{\alpha}$ cells, providing evidence that its proapoptotic effects are mediated through the inhibition of EGFR/ERK/PKM2 signaling pathways.

Influence of Palm Kernel Meal Inclusion and Exogenous Enzyme Supplementation on Growth Performance, Energy Utilization, and Nutrient Digestibility in Young Broilers

  • Abdollahi, M.R.;Hosking, B.J.;Ning, D.;Ravindran, V.
    • Asian-Australasian Journal of Animal Sciences
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    • v.29 no.4
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    • pp.539-548
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    • 2016
  • The objective of the present study was to investigate the influence of palm kernel meal (PKM) inclusion and exogenous enzyme supplementation on growth performance, nitrogen-corrected apparent metabolizable energy (AMEn), coefficient of apparent ileal digestibility (CAID) and total tract retention of nutrients in young broilers fed corn-based diets. Four inclusion levels of PKM (no PKM [PKM0], 8% [PKM8], 16% [PKM16], and 24% [PKM24]) and two enzyme additions were evaluated in a $4{\times}2$ factorial arrangement of treatments. A total of 384, one-d-old male broilers (Ross 308) were individually weighed and allocated to 48 cages (eight broilers/cage), and cages were randomly assigned to eight dietary treatments. Results indicated that the inclusion of 8% and 16% PKM increased (p<0.05) the weight gain compared to the PKM0 diet. Birds fed the PKM8 diets had the highest (p<0.05) feed intake. Weight gain and feed intake were severely reduced (p<0.05) by feeding the PKM24 diet. Enzyme supplementation increased weight gain (p<0.05), independent of PKM inclusion level. In PKM0 and PKM8 diets, enzyme addition significantly (p<0.05) lowered feed conversion ratio (FCR); whereas enzyme addition had no effect on FCR of birds fed PKM16 and PKM24 diets. In PKM0 and PKM16 diets, enzyme addition significantly (p<0.05) increased CAID of nitrogen and energy but had no effect in the PKM8 and PKM24 diets. Inclusion of PKM into the basal diet, irrespective of inclusion level, enhanced (p<0.05) starch and fat digestibility. Inclusion of PKM at 16% and 24% resulted in similar CAID of neutral detergent fiber (NDF) but higher (p<0.05) than that of the PKM0 and PKM8 diets. Enzyme addition, regardless of the level of PKM inclusion, significantly (p<0.05) increased CAID of NDF. There was a significant (p<0.05) decrease in AMEn with PKM inclusion of 24%. The present data suggest that inclusion of PKM in broiler diets could be optimized if PKM-containing diets are formulated based on digestible amino acid contents and supplemented with exogenous enzymes. If amino acid digestibility and AME of PKM considered in the formulation, it can be included in broiler diets up to 16% with no deleterious effects on growth performance.

Effect of Dietary β-Mannanase Supplementation and Palm Kernel Meal Inclusion on Laying Performance and Egg Quality in 73 Weeks Old Hens

  • Lee, Jun Yeob;Kim, Sang Yun;Lee, Jae Hwan;Lee, Jeong Heon;Ohh, Sang Jip
    • Journal of Animal Science and Technology
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    • v.55 no.2
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    • pp.115-122
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    • 2013
  • This study was conducted to evaluate the effect of dietary ${\beta}$-mannanase supplementation and palm kernel meal (PKM) inclusion (5%) on laying performance, egg quality and nutrient utilizability of laying hens with 73 weeks of age. A total of 240 Lohmann brown laying hens with average 77.5% egg production were randomly allocated with 60 hens per treatment, 4 replicates per treatment and 15 hens per replicate. Experimental design was a completely randomized design with $2{\times}2$ factorial arrangement, with the factors being (1) two levels of PKM (0 vs. 5%) and (2) with or without dietary ${\beta}$-mannanase (480 IU/kg of diet CTCzyme$^{(R)}$) supplementation. All hens were housed in cages ($35cmW{\times}35cmD{\times}40cmH$) with 2 hens per cage for six weeks feeding trial. Laying performance was recorded daily during feeding trial. Egg quality, nutrients utilizability and blood assays were done at the end of feeding trial. Egg production was improved (P<0.05) by both dietary PKM inclusion and ${\beta}$-mannanase combined supplementation. Either ${\beta}$-mannanase or PKM did not affect feed intakes and feed conversion ratio of all diets. Egg weight of hens fed diet containing 5% of PKM had heavier (P<0.05) eggs compared with hens fed without PKM. Albumen height was improved (P<0.05) by dietary mannanase supplementation. Crude fat utilization of 5% PKM diet was higher than that of no PKM diet regardless of ${\beta}$-mannanase supplementation. Both DM and total carbohydrate utilization were decreased (P<0.05) in hens fed 5% PKM diet. Serum IgG and yolk IgY contents of PKM groups were lower (P<0.05) than those of no PKM groups. This result showed that 5% PKM diet, independent of dietary ${\beta}$-mannanase supplementation, was able to improve egg production. In addition, dietary ${\beta}$-mannanase supplementation could be used for improving the albumen height of eggs.

Knockdown of Pyruvate Kinase M Inhibits Cell Growth and Migration by Reducing NF-κB Activity in Triple-Negative Breast Cancer Cells

  • Ma, Chaobing;Zu, Xueyin;Liu, Kangdong;Bode, Ann M.;Dong, Zigang;Liu, Zhenzhen;Kim, Dong Joon
    • Molecules and Cells
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    • v.42 no.9
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    • pp.628-636
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    • 2019
  • Altered genetic features in cancer cells lead to a high rate of aerobic glycolysis and metabolic reprogramming that is essential for increased cancer cell viability and rapid proliferation. Pyruvate kinase muscle (PKM) is a rate-limiting enzyme in the final step of glycolysis. Herein, we report that PKM is a potential therapeutic target in triple-negative breast cancer (TNBC) cells. We found that PKM1 or PKM2 is highly expressed in TNBC tissues or cells. Knockdown of PKM significantly suppressed cell proliferation and migration, and strongly reduced S phase and induced G2 phase cell cycle arrest by reducing phosphorylation of the CDC2 protein in TNBC cells. Additionally, knockdown of PKM significantly suppressed $NF-{\kappa}B$ (nuclear factor kappa-light-chain-enhancer of activated B cells) activity by reducing the phosphorylation of p65 at serine 536, and also decreased the expression of $NF-{\kappa}B$ target genes. Taken together, PKM is a potential target that may have therapeutic implications for TNBC cells.

The effect of palm kernel meal supplementation in the diet on the growth performance and meat quality of swine, and on the level of odorous compounds and bacterial communities in swine manure

  • Hwang, Ok-Hwa;Lee, Yoo-Kyoung;Cho, Sung-Back;Han, Deug-Woo;Lee, Sang-Ryoung;Kwag, Jeong-Hoon;Park, Sung-Kwon
    • Korean Journal of Agricultural Science
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    • v.43 no.5
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    • pp.777-787
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    • 2016
  • In the present study, we aimed to investigate the effect of dietary supplementation of palm kernel meal (PKM), as a fermentable carbohydrate source, on the growth performance, meat quality, concentration of odorous compound, and changes in bacterial community in swine manure. Swine (average initial body weight of $51.36{\pm}1.02kg$) were fed diet which included three levels of PKM (0, 2 and 4%), and their manure samples were collected from the slurry pit. Growth performance and meat quality were not affected by PKM treatments (p > 0.05). Levels of phenols and indoles were decreased in the 2 and 4% PKM treatments compared to 0% PKM (control; p < 0.05). Especially, compared to the control, the 2% PKM group showed decreased levels of phenols by 35% and indoles by 34%. Among the dominant bacterial genera, the main change in relative abundance occurred in those belonging to the Firmicutes phylum in PKM treatments. Terrisporobacter and Clostridium were decreased in the PKM groups compared to the control. However, the relative abundance of Intestinibacter, AM406061_g, Coprococcus_g2, Phascolarcotobacterium, EF401875_g, Lactobacillus, and Streptococcus were increased in the PKM group compared to control. Taken together, administration of PKM had a beneficial effect on reducing production of odorous compounds in swine manure, possibly by modulating the communities of predominantly carbohydrate-utilizing bacteria in the large intestine of swine.

A Novel Pyruvate Kinase M2 Activator Compound that Suppresses Lung Cancer Cell Viability under Hypoxia

  • Kim, Dong Joon;Park, Young Soo;Kim, Nam Doo;Min, Sang Hyun;You, Yeon-Mi;Jung, Yuri;Koo, Han;Noh, Hanmi;Kim, Jung-Ae;Park, Kyung Chan;Yeom, Young Il
    • Molecules and Cells
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    • v.38 no.4
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    • pp.373-379
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    • 2015
  • Pyruvate kinase M2 isoform (PKM2), a rate-limiting enzyme in the final step of glycolysis, is known to be associated with the metabolic rewiring of cancer cells, and considered an important cancer therapeutic target. Herein, we report a novel PKM2 activator, PA-12, which was identified via the molecular docking-based virtual screening. We demonstrate that PA-12 stimulates the pyruvate kinase activity of recombinant PKM2 in vitro, with a half-maximal activity concentration of $4.92{\mu}M$, and effectively suppresses both anchorage-dependent and -independent growth of lung cancer cells in non-essential amino acid-depleted medium. In addition, PA-12 blocked the nuclear translocalization of PKM2 in lung cancer cells, resulting in the inhibition of hypoxia response element (HRE)-mediated reporter activity as well as hypoxia-inducible factor 1 (HIF-1) target gene expression, eventually leading to the suppression of cell viability under hypoxia. We also verified that the effects of PA-12 were dependent on PKM2 expression in cancer cells, demonstrating the specificity of PA-12 for PKM2 protein. Taken together, our data suggest that PA-12 is a novel and potent PKM2 activator that has therapeutic implications for lung cancer.

Effects of Operating Variables on Sorption Capacity of CO2 Absorbents for SEWGS Process (SEWGS 공정용 CO2 흡수제들의 흡수능력에 미치는 조업변수들의 영향)

  • Ryu, Ho-Jung;Kim, Hyo-Sung;Lee, Seung-Yong;Lee, Dong-Ho;Kim, Jae-Chang
    • Korean Chemical Engineering Research
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    • v.50 no.6
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    • pp.994-1001
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    • 2012
  • The Effects of operating variables on reactivity of two $CO_2$ absorbents (PKM1-SU and P4-600) for SEWGS process were investigated in a pressurized fluidized bed reactor. For both $CO_2$ absorbents, $CO_2$ sorption capacity decreased as the number of absorption-regeneration cycles increased. PKM1-SU absorbent represented higher $CO_2$ sorption capacity than that of P4-600 absorbent. However, P4-600 absorbent represented better performance than PKM1-SU absorbent from the view points of regeneration temperature and regeneration rate. For PKM1-SU absorbent, $CO_2$ sorption capacity increased as the steam concentration increased. However, $CO_2$ sorption capacity increased initially as the steam concentration increased from 5% to 10%, but maintained thereafter for P4-600 absorbent. For both $CO_2$ absorbents, $CO_2$ sorption capacity increased as the final regeneration temperature increased. For PKM1-SU absorbent, $CO_2$ sorption capacity increased as the pressure increased and the increment tendency was drastic at higher pressure than 15 bar.

Effect of Partial Replacement of Soybean Meal with Palm Kernel Meal and Copra Meal on Growth Performance, Nutrient Digestibility and Carcass Characteristics of Finishing Pigs

  • Kim, B.G.;Lee, J.H.;Jung, H.J.;Han, Y.K.;Park, K.M.;Han, In K.
    • Asian-Australasian Journal of Animal Sciences
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    • v.14 no.6
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    • pp.821-830
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    • 2001
  • To study the effects of partial replacement of soybean meal (SBM) with palm kernel meal (PKM) and copra meal (CM) on growth performance, nutrient digestibility and carcass characteristics in finishing pigs, a total of 150 crossbred pigs (Landrace$\times$Duroc$\times$Yorkshire; average $52.11{\pm}1.08kg$ body weight) were alloted to five treatments, in a randomized block design. The treatments included 1) Control: without PKM or CM, 2) PKM2: 2% of palm kernel meal, 3) PKM4: 4% palm kernel meal, 4) CM2: 2% of copra meal, 5) CM4: 4% of copra meal. During the early finishing period (52~74 kg), growth performance was better in CM diets than in PKM diets or control diet, and in overall period (74~100 was lower (p<0.05) in PKM4 diet than the other diets. Nutrient digestibilies of PKM or CM substituted diets showed the tendency to be lower than those of control diet. In the early finishing period, total amino acid digestibilities of PKM and CM diets had the tendency to be lower than control diet, and in the late finishing period, they were lower (p<0.05) than control diet. Carcass length was longer (p<0.05) in the pigs fed 2% CM than in the pigs fed 4% PKM diet, but other carcass characteristics were not different among treatments. Although the dietary C14:0 content affected (p<0.05) on the C14:0 content in the carcass, the inclusion of PKM or CM in the diet did not affect the total saturated fatty acids and unsaturated fatty acids in the backfat of finishing pigs. Although it was not significant, supplementation of CM at the 2% and 4% of control group tended to decrease feed cost per kg weight gain by 2.89 to 1.42%, respectively. In conclusion, copra meal can be a valuable source of protein in the diet for finishing pigs and may replace other protein sources in pig diets to a considerable extent.

Effects and Mechanisms of Metformin on the Proliferation of Esophageal Cancer Cells In Vitro and In Vivo

  • Tang, Jian-Cai;An, Rui;Jiang, Yi-Qing;Yang, Jian
    • Cancer Research and Treatment
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    • v.49 no.3
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    • pp.778-789
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    • 2017
  • Purpose The purpose of this study was to observe the effects of metformin on human esophageal cancer cell and to investigate its possible mechanisms. Materials and Methods Cell viability was detected by using a Cell Counting Kit-8, while cell cycle and apoptosis were assessed by flow cytometry and western blot was used to measure the expression of the related proteins. RNAi was used to knockout pyruvate kinase muscle isozyme 2 (PKM2). An Eca109 tumor model was established to evaluate the antitumor effect in vivo. Immunohistochemistry was determined based on the expression of PKM2 and Bim in tumor tissues. Tunnel was used to assess tumor cell apoptosis. Results Esophageal cancer cells viability was reduced after metformin treatment. The cell cycle was arrested in the G0/G1 phase, apoptosis was induced, caspase 3 was activated, caspase 9 was downregulated, and the pro-apoptotic protein Bim increased. Further study revealed that metformin could suppress the expression of insulin-like growth factor 1 receptor and its downstream proteins, phosphoinositide 3-kinase (PI3K), protein kinase B (AKT/PKB), phosphorylation of AKT (pAKT), mammalian target of rapamycin (mTOR), p70S6K, and PKM2. Insulin-like growth factor 1 partly reversed metfromin-induced apoptosis and attenuated the repression effect of metfomin to PI3K, pAKT, and PKM2. Knockout PKM2 resulted in the activation of caspase 3, down-regulation of caspase 9, and increased expression of Bim. In the Eca109 xenograft model, metformin significantly reduced tumor growth. Furthermore, we found that metformin treatment increased the rate of apoptosis, down-regulation of PKM2, and up-regulation of Bim in tumor tissues. Conclusion Metformin restrained esophageal cancer cell proliferation partly by suppressing the PI3K/AKT/mTOR pathway.

PKM2 Regulates Hepatocellular Carcinoma Cell Epithelial-mesenchymal Transition and Migration upon EGFR Activation

  • Fan, Fang-Tian;Shen, Cun-Si;Tao, Li;Tian, Chao;Liu, Zhao-Guo;Zhu, Zhi-Jie;Liu, Yu-Ping;Pei, Chang-Song;Wu, Hong-Yan;Zhang, Lei;Wang, Ai-Yun;Zheng, Shi-Zhong;Huang, Shi-Le;Lu, Yin
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.5
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    • pp.1961-1970
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    • 2014
  • Pyruvate kinase isozyme type M2 (PKM2) was first found in hepatocellular carcinoma (HCC), and its expression has been thought to correlate with prognosis. A large number of studies have demonstrated that epithelial-mesenchymal transition (EMT) is a crucial event in hepatocellular carcinoma (HCC) and associated metastasis, resulting in enhanced malignancy of HCC. However, the roles of PKM2 in HCC EMT and metastasis remain largely unknown. The present study aimed to determine the effects of PKM2 in EGF-induced HCC EMT and elucidate the molecular mechanisms in vitro. Our results showed that EGF promoted EMT in HCC cell lines as evidenced by altered morphology, expression of EMT-associated markers, and enhanced invasion capacity. Furthermore, the present study also revealed that nuclear translocation of PKM2, which is regulated by the ERK pathway, regulated ${\beta}$-catenin-TCF/LEF-1 transcriptional activity and associated EMT in HCC cell lines. These discoveries provide evidence of novel roles of PKM2 in the progression of HCC and potential therapeutic target for advanced cases.