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https://www.readbyqxmd.com/read/29788929/resveratrol-induces-autophagy-dependent-apoptosis-in-hl-60-cells
#1
Yingying Fan, Jen-Fu Chiu, Jing Liu, Yan Deng, Cheng Xu, Jun Zhang, Guanwu Li
BACKGROUND: All known mechanisms of apoptosis induced by resveratrol act through cell cycle arrest and changes in mitochondrial membrane potential. It is currently unknown whether resveratrol-induced apoptosis is associated with other physiological processes, such as autophagy. METHODS: Apoptosis-related markers involved in the intrinsic and extrinsic apoptotic pathways, and autophagic markers were detected by using western blotting and immunofluorescence. Mitochondrial membrane potential was assayed by flow cytometry...
May 22, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29782351/role-of-lkb1-in-migration-and-invasion-of-cr-vi-transformed-human-bronchial-epithelial-beas-2b-cells
#2
Jian Lu, Zhongping Zhou, Miaomiao Tang, Haijun Shen, Yi Liu, Jin Wang, Yewen Jiang, Yifan Chen, Zhanao Wu
Hexavalent chromium [Cr(VI)] is a common human carcinogen associated with lung cancer and other pulmonary diseases as exposure to excessive Cr(VI) induces malignant transformation in human lung epithelial cells. The mechanism underlying its carcinogenicity is unclear in terms of how it facilitates metastases. Cr(VI) compounds are reported to briefly promote cell migration in a concentration-dependent manner and oncogene liver kinase B1 (LKB1) was reduced in Cr(VI)-transformed cells. Overexpression of LKB1 in Beas-2B-Cr [Cr(VI) malignantly transformed Beas-2B cells] suppressed cell migration and invasion and inactivated FAK, Src, MMP-2, GSK3β, β-catenin, and HEF1, which contribute to cell migration and invasion...
May 18, 2018: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29777910/differentially-expressed-novel-alternatively-spliced-transcript-variant-of-tumor-suppressor-stk11-gene-in-mouse
#3
Hassan Mubarak Ishqi, Tarique Sarwar, Mohammed Amir Husain, Sayeed Ur Rehman, Mohammad Tabish
Serine/threonine kinase 11 (STK11) is a protein kinase that is encoded by Stk11 gene located on chromosome 19 and 10 in humans and mouse respectively. It acts as a master kinase of adenine monophosphate-activated protein kinase (AMPK) pathway that coordinates the regulation of cellular energy metabolism and cell division. STK11 exerts effect by activating more than 14 kinases including AMPK and AMPK-related kinases. It is also known to regulate cell polarity and acts as tumor suppressor. Alternative splicing of pre-mRNA is a mechanism which results in multiple transcript variants of a single gene...
May 16, 2018: Gene
https://www.readbyqxmd.com/read/29773717/stk11-lkb1-mutations-and-pd-1-inhibitor-resistance-in-kras-mutant-lung-adenocarcinoma
#4
Ferdinandos Skoulidis, Michael E Goldberg, Danielle M Greenawalt, Matthew D Hellmann, Mark M Awad, Justin F Gainor, Alexa B Schrock, Ryan J Hartmaier, Sally E Trabucco, Laurie Gay, Siraj M Ali, Julia A Elvin, Gaurav Singal, Jeffrey S Ross, David Fabrizio, Peter M Szabo, Han Chang, Ariella Sasson, Sujaya Srinivasan, Stefan Kirov, Joseph Szustakowski, Patrik Vitazka, Robin Edwards, Jose A Bufill, Neelesh Sharma, Sai-Hong I Ou, Nir Peled, David R Spigel, Hira Rizvi, Elizabeth Jimenez Aguilar, Brett W Carter, Jeremy Erasmus, Darragh F Halpenny, Andrew J Plodkowski, Niamh M Long, Mizuki Nishino, Warren L Denning, Ana Galan-Cobo, Haifa Hamdi, Taghreed Hirz, Pan Tong, Jing Wang, Jaime Rodriguez-Canales, Pamela A Villalobos, Edwin R Parra, Neda Kalhor, Lynette M Sholl, Jennifer L Sauter, Achim A Jungbluth, Mari Mino-Kenudson, Roxana Azimi, Yasir Y Elamin, Jianjun Zhang, Giulia C Leonardi, Fei Jiang, Kwok-Kin Wong, J Jack Lee, Vassiliki A Papadimitrakopoulou, Ignacio I Wistuba, Vincent A Miller, Garrett M Frampton, Jedd D Wolchok, Alice T Shaw, Pasi A Jänne, Philip J Stephens, Charles M Rudin, William J Geese, Lee A Albacker, John V Heymach
KRAS is the most common oncogenic driver in lung adenocarcinoma (LUAC). We previously reported that STK11/LKB1 (KL) or TP53 (KP) co-mutations define distinct subgroups of KRAS-mutant LUAC. Here, we examine the efficacy of PD-1 inhibitors in these subgroups. Objective response rates to PD-1 blockade differed significantly among KL (7.4%), KP (35.7%), and K-only (28.6%) subgroups (P<0.001) in the SU2C cohort (174 patients) with KRAS-mutant LUAC and in patients treated with nivolumab in the CheckMate-057 phase 3 trial (0% vs 57...
May 17, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29763913/intraventricular-injection-of-lkb1-inhibits-the-formation-of-diet-induced-obesity-in-rats-by-activating-the-ampk-pomc-neurons-sympathetic-nervous-system-axis
#5
Pengjiao Xi, Jianying Du, Huimin Liang, Jie Han, Zhaoxia Wu, Haomin Wang, Lu He, Qiming Wang, Haize Ge, Yongmei Li, Jie Xue, Derun Tian
BACKGROUND/AIMS: Obesity is increasingly becoming a major public health problem worldwide. Peripheral LKB1 inhibits white fat generation, but the effect of central LKB1 on diet-induced obesity (DIO) is unknown. Therefore, we examined whether LKB1 over-expression in the hypothalamus can inhibit the development of obesity. METHODS: Adult male Sprague-Dawley rats were anesthetized and placed in a stereotaxic apparatus. LKB1-AAV-EGFP (2.0 × 108 or 2.0 × 1010 vector genomes) or Control-AAV-EGFP (2...
May 9, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29740932/antagonizing-peroxisome-proliferator-activated-receptor-%C3%AE-facilitates-m1-to-m2-shift-of-microglia-by-enhancing-autophagy-via-the-lkb1-ampk-signaling-pathway
#6
Juan Ji, Teng-Fei Xue, Xu-Dong Guo, Jin Yang, Ruo-Bing Guo, Juan Wang, Ji-Ye Huang, Xiao-Jie Zhao, Xiu-Lan Sun
Microglia-mediated neuroinflammation plays a dual role in various brain diseases due to distinct microglial phenotypes, including deleterious M1 and neuroprotective M2. There is growing evidence that the peroxisome proliferator-activated receptor γ (PPARγ) agonist rosiglitazone prevents lipopolysaccharide (LPS)-induced microglial activation. Here, we observed that antagonizing PPARγ promoted LPS-stimulated changes in polarization from the M1 to the M2 phenotype in primary microglia. PPARγ antagonist T0070907 increased the expression of M2 markers, including CD206, IL-4, IGF-1, TGF-β1, TGF-β2, TGF-β3, G-CSF, and GM-CSF, and reduced the expression of M1 markers, such as CD86, Cox-2, iNOS, IL-1β, IL-6, TNF-α, IFN-γ, and CCL2, thereby inhibiting NFκB-IKKβ activation...
May 8, 2018: Aging Cell
https://www.readbyqxmd.com/read/29733904/c1qtnf1-attenuates-angiotensin-ii-induced-cardiac-hypertrophy-via-activation-of-the-ampka-pathway
#7
Leiming Wu, Lu Gao, Dianhong Zhang, Rui Yao, Zhen Huang, Binbin Du, Zheng Wang, Lili Xiao, Pengcheng Li, Yapeng Li, Cui Liang, Yanzhou Zhang
RATIONALE: Complement C1q tumor necrosis factor related proteins (C1QTNFs) have been reported to have diverse biological influence on the cardiovascular system. C1QTNF1 is a member of the CTRP superfamily. C1QTNF1 is expressed in the myocardium; however, its function in myocytes has not yet been investigated. OBJECTIVE: To systematically investigate the roles of C1QTNF1 in angiotensin II (Ang II)-induced cardiac hypertrophy. METHODS AND RESULTS: C1QTNF1 knock-out mice were used with the aim of determining the role of C1QTNF1 in cardiac hypertrophy in the adult heart...
May 4, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29706079/modulation-of-ampk-dependent-lipogenesis-mediated-by-p2x7r-nlrp3-inflammasome-activation-contributes-to-the-amelioration-of-alcoholic-liver-steatosis-by-dihydroquercetin
#8
Yu Zhang, Quan Jin, Xia Li, Jiang Min, Ben-Wen Cui, Kai-Li Xia, Yan-Ling Wu, Li-Hua Lian, Ji-Xing Nan
Dihydroquercetin (TAX) is the most abundant dihydroflavone found in onions, milk thistle and Douglas fir bark. We investigated whether TAX could inhibit the lipid accumulation in alcoholic liver steatosis in vivo and in vitro. An in vivo model was established by intragastrically treating mice with ethanol, and an in vitro model was created by treating HepG2 cells with ethanol. TAX regulated SREBP1 and ACC expression via elevating LKB1/AMPK phosphorylation. Also, TAX upregulated SIRT1 expression, which suppressed by ethanal intake...
April 28, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29698519/the-loss-of-the-kinases-sada-and-sadb-results-in-early-neuronal-apoptosis-and-a-reduced-number-of-progenitors
#9
Pratibha Dhumale, Sindhu Menon, Joanna Chiang, Andreas W Püschel
The neurons that form the mammalian neocortex originate from progenitor cells in the ventricular (VZ) and subventricular zone (SVZ). Newborn neurons are multipolar but become bipolar during their migration from the germinal layers to the cortical plate (CP) by forming a leading process and an axon that extends in the intermediate zone (IZ). Once they settle in the CP, neurons assume a highly polarized morphology with a single axon and multiple dendrites. The AMPK-related kinases SadA and SadB are intrinsic factors that are essential for axon formation during neuronal development downstream of Lkb1...
2018: PloS One
https://www.readbyqxmd.com/read/29694959/prognostic-impact-of-dna-repair-protein-expression-in-non-small-cell-lung-cancers-treated-with-platinum-based-chemotherapy-and-subsequent-curative-lung-resection
#10
Junghoon Shin, Kyu Sang Lee, Kyung Ah Yoh, Hyun Jin Cho, Moon Ki Choi, Se Hyun Kim, Yu Jung Kim, Jin-Haeng Chung, Sukki Cho, Kwhanmien Kim, Sanghoon Jheon, Ho Il Yoon, Jae Ho Lee, Choon-Taek Lee, Jong Seok Lee
OBJECTIVE: Multimodal treatments that include preoperative platinum-based chemotherapy are fundamental to the treatment of advanced non-small cell lung cancer (NSCLC). This study aimed to investigate the predictive value of DNA repair protein expression in surgically resected NSCLCs in terms of prognosis and responses to platinum-containing chemotherapy. METHODS: This retrospective study included 136 patients with NSCLC who were treated with preoperative platinum-based chemotherapy, followed by curative lung resection...
April 25, 2018: Oncology
https://www.readbyqxmd.com/read/29693104/c-phycocyanin-inhibits-hepatic-gluconeogenesis-and-increases-glycogen-synthesis-via-activating-akt-and-ampk-in-insulin-resistance-hepatocytes
#11
Zhiheng Ren, Zhifei Xie, Danni Cao, Mufeng Gong, Lei Yang, Zhu Zhou, Yu Ou
C-Phycocyanin (C-PC), a kind of blue protein isolated from Spirulina platensis, can ameliorate hyperglycemia, but its effects on gluconeogenesis and glycogenesis are unknown. In the present study, we investigated the effects and underlying mechanisms of C-PC on gluconeogenesis and glycogenesis in insulin resistant hepatocytes. Insulin resistance was induced by high glucose (HG) in human hepatocellular carcinoma (HepG2) cells. C-PC ameliorated glucose production and phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) expression in HG-induced insulin resistant HepG2 cells...
April 25, 2018: Food & Function
https://www.readbyqxmd.com/read/29674003/tanshinone-iia-suppresses-fc%C3%AE%C2%B5ri-mediated-mast-cell-signaling-and-anaphylaxis-by-activation-of-the-sirt1-lkb1-ampk-pathway
#12
Xian Li, Soon Jin Park, Fansi Jin, Yifeng Deng, Ju Hye Yang, Jae-Hoon Chang, Dong-Young Kim, Jung-Ae Kim, Youn Ju Lee, Makoto Murakami, Kun Ho Son, Hyeun Wook Chang
AMP-activated protein kinase (AMPK) and its upstream mediators liver kinase B1 (LKB1) and sirtuin 1 (Sirt1) are generally known as key regulators of metabolism. We have recently reported that the AMPK pathway negatively regulates mast cell activation and anaphylaxis. Tanshinone IIA (Tan IIA), an active component of Salvia miltiorrhiza extract that is currently used for the treatment of cardiovascular and cerebrovascular diseases, shows anti-diabetic activity and improves insulin resistance in db/db mice through activation of AMPK...
June 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29642873/bexarotene-inhibits-the-viability-of-non-small-cell-lung-cancer-cells-via-slc10a2-ppar%C3%AE-pten-mtor-signaling-pathway
#13
Xinghao Ai, Feng Mao, Shengping Shen, Yang Shentu, Jiejun Wang, Shun Lu
BACKGROUND: Thirty to 40 % of non-small cell lung cancer (NSCLC) patients developed higher hypertriglyceridemia in the process of treatment with bexarotene. And bioinformatics studies discovered that the expression of slc10a2 was increased in high-grade hypertriglyceridemia patients. So, we will explore the mechanism which may involve in this process. METHODS: We constructed slc10a2 overexpressed A549 cells and H1299 cells as cell models, normal A549 cells and H1299 cells as control...
April 11, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29628399/lkb1-controlling-quiescence-and-genomic-integrity-at-home
#14
Carmen Berasain, Matías A Ávila
The pleiotropic liver kinase B1 (LKB1) controls metabolism, cell polarity, and proliferation in an apparently cell- and context-specific manner. A recent study in Cell Reports has demonstrated that LKB1 is essential to maintain the characteristic quiescence of the liver and to secure genomic integrity during liver regeneration independently of AMPK.
April 5, 2018: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/29601127/lkb1-obliterates-snail-stability-and-inhibits-pancreatic-cancer-metastasis-in-response-to-metformin-treatment
#15
Lele Song, Jingyu Guo, Renxu Chang, Xiaobo Peng, Jie Li, Xiaorong Xu, Xianbao Zhan, Lixing Zhan
Metastasis to distant organs is a particularly ominous feature of most malignant cancer. LKB1 (also known as STK11) has been identified as a tumor suppressor in several types of cancers. Here, we show that LKB1 is at low level and negatively associated with poor clinical outcomes in pancreatic cancer (PC). LKB1 is inversely correlated with Snail protein in PC, in which loss of LKB1 facilitates metastasis through elevating Snail protein level. Furthermore, LKB1 boosts Snail interacting with E3 ligase FBXL14, leading to increasing ubiquitin-mediated Snail degradation...
March 30, 2018: Cancer Science
https://www.readbyqxmd.com/read/29595075/epigallocatechin-3-gallate-rich-green-tea-extract-ameliorates-fatty-liver-and-weight-gain-in-mice-fed-a-high-fat-diet-by-activating-the-sirtuin-1-and-amp-activating-protein-kinase-pathway
#16
Ui-Jin Bae, John Park, Il Woon Park, Byung Min Chae, Mi-Ra Oh, Su-Jin Jung, Geon-Seek Ryu, Soo-Wan Chae, Byung-Hyun Park
The prevalence of metabolic diseases has risen globally in parallel with the obesity epidemic over the past few decades. Green tea has been reported to have metabolically beneficial effects on obesity; however, the mechanism by which green tea regulates lipid metabolism is not clearly understood. Male c57BL/6 mice were fed a normal chow diet, a high-fat diet (HFD), or an HFD supplemented with various doses of epigallocatechin gallate-rich green tea extract (GTE) for 12 weeks. GTE supplementation reduced body weight gain, prevented hepatic fat accumulation, decreased hypertriglyceridemia, and improved hyperglycemia and insulin resistance in HFD-fed mice...
March 29, 2018: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/29580896/p53-and-glucose-metabolism-an-orchestra-to-be-directed-in-cancer-therapy
#17
REVIEW
Ana Sara Gomes, Helena Ramos, Joana Soares, Lucília Saraiva
Metabolic reprogramming is a hallmark of cancer with a strong impact on tumor cell survival, proliferation, dissemination, and resistance to therapy. As such, it has represented a promising therapeutic target for cancer. Although cancer cells may exhibit a wide range of metabolic profiles, the enhancement of aerobic glycolysis to generate lactate and ATP (Warburg effect) is a cancer-associated trait, which is under regulation of both oncogenes and tumor suppressor genes. Particularly, the tumor suppressor protein p53 was shown to revert the Warburg effect, and to negatively influence the oncogenic metabolic adaption of cancer cells...
March 23, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29573522/liver-kinase-b1-suppresses-growth-of-lung-cancer-cells-through-sonic-hedgehog-signaling-pathway
#18
Kuiyuan Song, Guanqun Zheng, Yue Zhao
Lung cancer is one of life-threatening cancers in the worldwide. Liver kinase B1 (LKB1) has been reported to be closely related to cancers, however, the underlying mechanism of LKB1 in lung cancer remains unclear. In our study, a LKB1 specific shRNA was employed to down-regulate LKB1 levels and a LKB1 over-expression plasmid was constructed to up-regulate LKB1 levels. Thereafter, growth of lung cancer cells was assessed by MTT assay and flow cytometry. Effects of LKB1 on the activation of sonic hedgehog (Shh) signaling pathway were detected by western blot...
March 24, 2018: Cell Biology International
https://www.readbyqxmd.com/read/29566977/co-suppresses-prostate-cancer-cell-growth-by-directly-targeting-lkb1-ampk-mtor-pathway-in-vitro-and-in-vivo
#19
Yutao Yan, Caiqi Du, Guohao Li, Lin Chen, Yubo Yan, Gang Chen, Weifeng Hu, Lei Chang
BACKGROUND: CO is a freely diffusible gas that acts as a physiological mediator of many biological and cellular processes, which has been shown to possess anticancer effect in many kinds of cancers. However, the effect of CO on prostate cancer has not been demonstrated. Therefore, we analyzed the antitumor activities and related mechanisms of CO on prostate cancer in vitro and in vivo. METHODS: Cell viability of LNCaP and PC-3 cells after CORM-2 treatment was measured by CCK-8 assay, whereas the ATP production were detected by ATP detection assay...
June 2018: Urologic Oncology
https://www.readbyqxmd.com/read/29563804/decreased-expression-of-lkb1-predicts-poor-prognosis-in-pancreatic-neuroendocrine-tumor-patients-undergoing-curative-resection
#20
Dezhi Li, Yu Zhou, Yanhui Liu, Ye Lin, Min Yu, Xin Lu, Bowen Huang, Zhonghai Sun, Zhixiang Jian, Baohua Hou
Background: Liver kinase B1 (LKB1) is a key regulatory protein of cellular metabolism, proliferation, and polarity. The present study aimed to characterize the expression pattern of LKB1 in pancreatic neuroendocrine tumors (pNETs) and evaluate the relationship between LKB1 expression and prognosis in pNETs. Patients and methods: We retrospectively analyzed the pathologic and clinical data of 71 pNET patients who underwent curative surgical resection in Guangdong General Hospital...
2018: OncoTargets and Therapy
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