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Lactate AND mTOR

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https://www.readbyqxmd.com/read/29932973/combinatorial-treatment-of-rhizoma-paridis-saponins-and-sorafenib-overcomes-the-intolerance-of-sorafenib
#1
Jingwen Yao, Shuli Man, Honghong Dong, Li Yang, Long Ma, Wenyuan Gao
Sorafenib, as a multi-kinase inhibitor, was the first FDA-approved anti- hepatocellular carcinoma (HCC) drug. Rhizoma Paridis saponins (RPS) as natural products have shown antitumor activity through regulation of glycolytic and lipid metabolism which was regarded as the side effect limited the utility of sorafenib. In this research, we tried to use metabolomics to verify the probability of combinatorial treatment of RPS and Sorafenib. As a result, Sorafenib + RPS increased the antitumor effect of sorafenib and RPS in H22 mice...
June 19, 2018: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29916308/the-mtor-pathway-regulates-pkm2-to-affect-glycolysis-in-esophageal-squamous-cell-carcinoma
#2
He Xiaoyu, Yin Yiru, Shi Shuisheng, Cheng Keyan, Yan Zixing, Cheng Shanglin, Wang Yuan, Cheng Dongming, Zhang Wangliang, Bai Xudong, Ma Jie
OBJECTIVES: Esophageal squamous cell carcinoma is a highly prevalent cancer withpoor survival rate and prognosis. Increasing evidence suggests an important role for metabolic regulation in treating esophageal squamous cell carcinoma, but the underlying mechanism remains unclear. The pyruvate kinase M2 isoform is a key enzyme in the energy production process, and the upregulation of pyruvate kinase M2 isoform also plays a crucial role in gene transcription and tumorigenesis. The mammalian target of rapamycin pathway regulates an array of cellular functions, including protein synthesis, metabolism, and cell proliferation...
January 1, 2018: Technology in Cancer Research & Treatment
https://www.readbyqxmd.com/read/29898734/knockdown-of-klf5-suppresses-hypoxia-induced-resistance-to-cisplatin-in-nsclc-cells-by-regulating-hif-1%C3%AE-dependent-glycolysis-through-inactivation-of-the-pi3k-akt-mtor-pathway
#3
Tianxiao Gong, Liuqing Cui, Haili Wang, Haoxun Wang, Na Han
BACKGROUND: Hypoxia-mediated chemoresistance has been regarded as an important obstacle in the development of cancer treatment. Knockdown of krüppel-like factor 5 (KLF5) was reported to inhibit hypoxia-induced cell survival and promote cell apoptosis in non-small cell lung cancer (NSCLC) cells via direct regulation of hypoxia inducible factor-1α (HIF-1α) expression. However, the roles of KLF5 in the development of hypoxia-induced cisplatin (DDP) resistance and its underlying mechanism in NSCLC cells remain to be further elucidated...
June 14, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29886375/down-regulation-of-mir-214-inhibits-proliferation-and-glycolysis-in-non-small-cell-lung-cancer-cells-via-down-regulating-the-expression-of-hexokinase-2-and-pyruvate-kinase-isozyme-m2
#4
Kejian Zhang, Mingrui Zhang, Hui Jiang, Fenglin Liu, Hongwei Liu, Yang Li
Glycolysis is a metabolic pathway that is enhanced in cancer cells. miR-214 plays an important role in cancer development and can modulate glycolysis. However, whether miR-214 can regulate glycolysis in non-small-cell lung cancer (NSCLC) cells has not yet been investigated. The expression levels of miR-214 in 7 NSCLC cell lines were measured by qRT-PCR. MTT assay was performed to evaluate the cell proliferation. Glucose consumption and lactate production were measured to assess the level of glycolysis. The expression of hexokinase 2 (HK2) and pyruvate kinase isozyme M2 (PKM2) was measured by qRT-PCR and western blot analysis...
June 6, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29844464/curcumin-decreases-warburg-effect-in-cancer-cells-by-down-regulating-pyruvate-kinase-m2-via-mtor-hif1%C3%AE-inhibition
#5
Farid Ahmad Siddiqui, Gopinath Prakasam, Shilpi Chattopadhyay, Asad Ur Rehman, Rayees Ahmad Padder, Mohammad Afaque Ansari, Rasha Irshad, Kailash Mangalhara, Rameshwar N K Bamezai, Mohammad Husain, Syed Mansoor Ali, Mohammad Askandar Iqbal
Warburg effect is an emerging hallmark of cancer cells with pyruvate kinase M2 (PKM2) as its key regulator. Curcumin is an extensively-studied anti-cancer compound, however, its role in affecting cancer metabolism remains poorly understood. Herein, we show that curcumin inhibits glucose uptake and lactate production (Warburg effect) in a variety of cancer cell lines by down-regulating PKM2 expression, via inhibition of mTOR-HIF1α axis. Stable PKM2 silencing revealed that PKM2 is required for Warburg effect and proliferation of cancer cells...
May 29, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29792195/histamine-activates-inflammatory-response-and-depresses-casein-synthesis-in-mammary-gland-of-dairy-cows-during-sara
#6
Guangjun Chang, Lailai Wang, Nana Ma, Wenwen Zhang, Huanmin Zhang, Hongyu Dai, Xiangzhen Shen
BACKGROUND: Mounting evidences observed that subacute ruminal acidosis (SARA) induced by high concentration (HC) diet increases the translocation of histamine from digestive tract into circulation causing a diverse of diseases in dairy cows. However, it is largely unknown how it does affect the function of mammary gland and milk quality. Hence, this study aims to observe the effects of histamine derived from the digestive tract on the inflammatory response and casein synthesis in the mammary glands during SARA...
May 23, 2018: BMC Veterinary Research
https://www.readbyqxmd.com/read/29785899/ragd-regulates-amino-acid-mediated-casein-synthesis-and-cell-proliferation-via-mtor-signalling-in-cow-mammary-epithelial-cells
#7
Ying Mu, Dongmei Zheng, Cong Wang, Wei Yu, Xiaonan Zhang
This research paper addresses the hypothesis that RagD is a key signalling factor that regulates amino acid (AA) mediated-casein synthesis and cell proliferation in cow mammary epithelial cells (CMECs). The expression of RagD was analysed at different times during pregnancy and lactation in bovine mammary tissue from dairy cows. We showed that expression of RagD at lactation period was higher (P < 0·05) than that at pregnancy period. When CMECs were treated with methionine (Met) or lysine (Lys), expression of RagD, β-casein (CSN2), mTOR and p-mTOR, and cell proliferation were increased...
May 2018: Journal of Dairy Research
https://www.readbyqxmd.com/read/29734265/vaspin-prevents-tumor-necrosis-factor-%C3%AE-induced-apoptosis-in-cardiomyocytes-by-promoting-autophagy
#8
Xuan Ke, Yanqin Hao, Bingong Li, Jin Zou, Xuelian Li, Chunying Wei, Fuyou Liu, Zhiyong Zhang
Visceral adipose tissue-derived serine protease inhibitor (Vaspin) is an adipocytokine that has been shown to exert anti-inflammatory effects and inhibits apoptosis under diabetic conditions. This study was designed to investigate the impact of vaspin on autophagy in tumor necrosis factor (TNF)-α-induced injury in cardiomyocytes and its cardioprotective effects in the pathogenesis of diabetic cardiomyopathy (DCM). H9C2 cells were treated with TNF-α with or without vaspin in vitro. Tumor necrosis factor-α treatment inhibited autophagy and promoted apoptosis in H9C2 cells after stimulating for 24 hours...
May 2018: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/29710456/vitexin-reverses-the-autophagy-dysfunction-to-attenuate-mcao-induced-cerebral-ischemic-stroke-via-mtor-ulk1-pathway
#9
Jin Jiang, Jingcun Dai, Hong Cui
Stroke, as a kind of acute cerebrovascular diseases, has greatly influenced the patients' quality of life and left a huge public health burden. Vitexin is a flavone C-glycoside (apigenin-8-C-?-D-glucopyranoside) present in several medicinal and other plants. This study aims to explore the role of vitexin in middle cerebral artery occlusion (MCAO)-induced cerebral ischemic stroke. The results showed that the MCAO-induced brain infarction was obviously decreased by vitexin. And the abnormal protein levels of Caspase-3, Bcl-2-associated X protein (Bax), antigen identified by monoclonal antibody (Ki-67) and B cell lymphoma 2 (Bcl-2) in MCAO model rats were reversed by vitexin...
March 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29685622/early-dietary-restriction-in-rats-alters-skeletal-muscle-tuberous-sclerosis-complex-ribosomal-s6-and-mitogen-activated-protein-kinase
#10
Kara L Calkins, Shanthie Thamotharan, Yun Dai, Bo-Chul Shin, Satish C Kalhan, Sherin U Devaskar
Intrauterine growth restriction is linked to decreased lean body mass and insulin resistance. The mammalian target of rapamycin (mTOR) regulates muscle mass and glucose metabolism; however, little is known about maternal dietary restriction and skeletal muscle mTOR in offspring. We hypothesized that early dietary restriction would decrease skeletal muscle mass and mTOR in the suckling rat. To test this hypothesis, ab libitum access to food or dietary restriction during gestation followed by postnatal cross-fostering to a dietary-restricted or ad libitum-fed rat dam during lactation generated 4 groups: control (CON), intrauterine dietary restricted (IUDR), postnatal dietary restricted (PNDR), and IUDR+PNDR (IPDR)...
March 23, 2018: Nutrition Research
https://www.readbyqxmd.com/read/29684851/mitochondrial-dna-content-reduction-induces-aerobic-glycolysis-and-reversible-resistance-to-drug-induced-apoptosis-in-sw480-colorectal-cancer-cells
#11
Jing-Jing Mou, Jin Peng, Ying-Ying Shi, Na Li, You Wang, Yuan Ke, Yun-Feng Zhou, Fu-Xiang Zhou
Mutations and reductions in mitochondrial DNA (mtDNA), which are frequent in human tumors, may contribute to enhancing their malignant phenotypes. However, the effects of mtDNA abnormalities in colorectal cancer remain largely unknown. In this study, mtDNA-reduced cell model was established by partial depletion of mtDNA in SW480 cells and the effects of mtDNA reduction in colorectal cancer cells were investigated. We found that mtDNA-reduced cells had enhanced glucose uptake and generated markedly higher level of lactate...
July 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29663499/resveratrol-inhibits-the-proliferation-and-induces-the-apoptosis-in-ovarian-cancer-cells-via-inhibiting-glycolysis-and-targeting-ampk-mtor-signaling-pathway
#12
Yu Liu, Lin Tong, Yan Luo, Xin Li, Gaowen Chen, Yifeng Wang
Aerobic glycolysis is an important metabolic rewiring in cancer cells to promote glucose uptake and lactate production, and targeting aerobic glycolysis becomes a promising therapeutic approach for cancer. Here we reported that a small polyphenol resveratrol exhibited profound anti-tumor efficacy on human ovarian cancer. Resveratrol markedly inhibited the proliferation, migration, and invasion of A2780 and SKOV3 ovarian cancer cells, while impaired glycolysis, and induced apoptosis in these cells. Exposure to resveratrol increased the expression and activation of AMPK and Caspase 3, and decreased the expression and activation of AMPK downstream kinase mTOR...
July 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29651246/lactone-component-from-ligusticum-chuanxiong-alleviates-myocardial-ischemia-injury-through-inhibiting-autophagy
#13
Gang Wang, Guoliang Dai, Jie Song, Maomao Zhu, Ying Liu, Xuefeng Hou, Zhongcheng Ke, Yuanli Zhou, Huihui Qiu, Fujing Wang, Nan Jiang, Xiaobin Jia, Liang Feng
The dysregulation of autophagy is associated with a series of cardiovascular diseases, such as myocardial ischemia injury. Lactone component from Ligusticum chuanxiong (LLC) is the major constituent of the traditional Chinese herb L. chuanxiong Hort., which has been reported to hold potential cardioprotective effects. In this study, to determine whether LLC protects the heart through regulation of autophagy, we explored the effects of LLC on cardioprotection and autophagy in myocardial ischemia injured rats and H9c2 cardiomyocytes...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29621758/targeting-mtor-by-cz415-inhibits-head-and-neck-squamous-cell-carcinoma-cells
#14
Jing Xie, Quan Li, Xi Ding, Yunyun Gao
BACKGROUND/AIMS: mTOR is an important therapeutic target for human head and neck squamous cell carcinoma (HNSCC). The current study tested the anti-HNSCC cell activity by a mTOR kinase inhibitor CZ415. METHODS: HNSCC cells were treated with CZ415. Cell death was tested by lactate dehydrogenase (LDH) assay and MTT assay. Cell proliferation was tested by BrdU ELISA assay and [H3] thymidine incorporation assay, with apoptosis assayed by the TUNEL staining. A Western blotting assay was applied to test autophagy-associated proteins, mTOR and signalings...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29589262/ocimum-basilicum-but-not-ocimum-gratissimum-present-cytotoxic-effects-on-human-breast-cancer-cell-line-mcf-7-inducing-apoptosis-and-triggering-mtor-akt-p70s6k-pathway
#15
Renan Gianoti Torres, Livia Casanova, Julia Carvalho, Mariah Celestino Marcondes, Sonia Soares Costa, Mauro Sola-Penna, Patricia Zancan
Breast cancer is the major cause of death by cancer in women worldwide and in spite of the many drugs for its treatment, there is still the need for novel therapies for its control. Ocimum species have been used by traditional medicine to control several diseases, including cancer. We have previously characterized the antidiabetic properties of the unfractionated aqueous leaf extracts of Ocimum basilicum (OB) and Ocimum gratissimum (OG), modulating glucose metabolism in diabetic mice. Since glucose metabolism is primordial for cancer cells survival, we hypothesized that these extracts are effective against cancer cells...
April 2018: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/29556372/3-epi-12%C3%AE-hydroxyfroside-a-new-cardenolide-induces-cytoprotective-autophagy-via-blocking-the-hsp90-akt-mtor-axis-in-lung-cancer-cells
#16
Yan Sun, Yong-Hao Huang, Feng-Ying Huang, Wen-Li Mei, Quan Liu, Cai-Chun Wang, Ying-Ying Lin, Canhua Huang, Yue-Nan Li, Hao-Fu Dai, Guang-Hong Tan
Rationale: Cardenolides have potential as anticancer drugs. 3'-epi-12β-hydroxyfroside (HyFS) is a new cardenolide structure isolated by our research group, but its molecular mechanisms remain poorly understood. This study investigates the relationship between its antitumor activities and autophagy in lung cancer cells. Methods: Cell growth and proliferation were detected by MTT, lactate dehydrogenase (LDH) release, 5-ethynyl-20-deoxyuridine (EDU) and colony formation assays. Cell apoptosis was detected by flow cytometry...
2018: Theranostics
https://www.readbyqxmd.com/read/29502357/qiliqiangxin-attenuates-hypoxia-induced-injury-in-primary-rat-cardiac-microvascular-endothelial-cells-via-promoting-hif-1%C3%AE-dependent-glycolysis
#17
Yanyan Wang, Xueting Han, Mingqiang Fu, Jingfeng Wang, Yu Song, Yuan Liu, Jingjing Zhang, Jingmin Zhou, Junbo Ge
Protection of cardiac microvascular endothelial cells (CMECs) against hypoxia injury is an important therapeutic strategy for treating ischaemic cardiovascular disease. In this study, we investigated the effects of qiliqiangxin (QL) on primary rat CMECs exposed to hypoxia and the underlying mechanisms. Rat CMECs were successfully isolated and passaged to the second generation. CMECs that were pre-treated with QL (0.5 mg/mL) and/or HIF-1α siRNA were cultured in a three-gas hypoxic incubator chamber (5% CO2 , 1% O2 , 94% N2 ) for 12 hours...
May 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29454865/inhibitory-effects-of-selenium-on-cadmium-induced-cytotoxicity-in-pc12-cells-via-regulating-oxidative-stress-and-apoptosis
#18
Kaniz Fatima Binte Hossain, Md Mostafizur Rahman, Md Tajuddin Sikder, Takeshi Saito, Toshiyuki Hosokawa, Masaaki Kurasaki
Purpose of this study is to investigate mechanism/s of cyto-protection by selenium (Na2 SeO3 ; Se4+ ) against cadmium (CdCl2 ; Cd2+ )-induced cytotoxicity using PC12 cells. In addition, Se (5, 10, 20 and 40 μM) and Cd (2.5, 5 and 10 μM)-induced cytotoxicity is determined. Cytotoxicity assays and western blot analyses confirmed that Se (≥10 μM) promotes autophagic cell death via inhibition of mTOR activation and p62 accumulation due to increase of cellular oxidative stress. On the other hand, co-presence of non-toxic Se (5 μM) and toxic Cd (5 μM) showed to increase cell viability, glutathione and glutathione peroxidase 1 (GPx1) levels, and to decrease DNA fragmentation and lactate dehydrogenase (LDH) activity compared to Cd-treated (5 μM) cells alone...
April 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29435722/l-arginine-regulates-protein-turnover-in-porcine-mammary-epithelial-cells-to-enhance-milk-protein-synthesis
#19
Qingquan Ma, Shengdi Hu, Makoto Bannai, Guoyao Wu
Milk is an important food for mammalian neonates, but its insufficient production is a nutritional problem for humans and other animals. Recent studies indicate that dietary supplementation with L-arginine (Arg) increases milk production in mammals, including sows, rabbits, and cows. However, the underlying molecular mechanisms remain largely unknown. The present study was conducted with porcine mammary epithelial cells (PMECs) to test the hypothesis that Arg enhances milk protein synthesis via activation of the mechanistic target of rapamycin (mTOR) cell signaling...
May 2018: Amino Acids
https://www.readbyqxmd.com/read/29420538/th-pok-regulates-mammary-gland-lactation-through-mtor-srebp-pathway
#20
Rui Zhang, Huimin Ma, Yuan Gao, Yanjun Wu, Yuemei Qiao, Ajun Geng, Cheguo Cai, Yingying Han, Yi Arial Zeng, Xiaolong Liu, Gaoxiang Ge
The Th-inducing POK (Th-POK, also known as ZBTB7B or cKrox) transcription factor is a key regulator of lineage commitment of immature T cell precursors. It is yet unclear the physiological functions of Th-POK besides helper T cell differentiation. Here we show that Th-POK is restrictedly expressed in the luminal epithelial cells in the mammary glands that is upregulated at late pregnancy and lactation. Lineage restrictedly expressed Th-POK exerts distinct biological functions in the mammary epithelial cells and T cells in a tissue-specific manner...
February 2018: PLoS Genetics
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