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autophagy AND pancreatitis

Wu Lv, Jialin Zhang, Ao Jiao, Bowen Wang, Baomin Chen, Jie Lin
It has been proved that human islet amyloid polypeptide (hIAPP), the main constituent of islet amyloid deposition, is one of the important factors which can induce type 2 diabetes or graft failure after islet transplantation. As there is no research on whether resveratrol degrading the amyloid deposition by its special chemical structure or enhancing autophagy had been published, we decided to detect the function of resveratrol in degrading the amyloid deposition in pancreatic beta cells. We established stable hIAPP-INS1 cell line via transfecting INS1 cells by lentivirus that overexpresses hIAPP...
October 12, 2018: Canadian Journal of Physiology and Pharmacology
Suresh Awale, Dya Fita Dibwe, Chandrasekar Balachandran, Shaimaa Fayez, Doris Feineis, Blaise Kimbadi Lombe, Gerhard Bringmann
PANC-1 human pancreatic cancer cells are characterized by their ability to proliferate aggressively under hypovascular and hypoxic conditions in the tumor microenvironment, displaying a remarkable tolerance to nutrition starvation. The antiausterity strategy is a new approach in anticancer drug discovery aiming at the identification of potent agents that inhibit preferentially the survival of tumor cells during a limited supply of nutrients and oxygen. The new 5,8'-coupled naphthyldihydroisoquinoline alkaloid ancistrolikokine E3 (4), isolated from the Congolese liana Ancistrocladus likoko, showed potent preferential cytotoxicity against PANC-1 cells under nutrient-deprived conditions, with a PC50 value of 2...
October 10, 2018: Journal of Natural Products
Sumate Ampawong, Duangnate Isarangkul, Onrapak Reamtong, Pornanong Aramwit
We recently demonstrated that in addition to its protective effect on pancreatic and adrenal biosynthesis, antioxidant properties of sericin decrease blood cholesterol levels and improve the liver mitochondrial architecture. However, little is known about the detailed mechanisms underlying these effects. Using proteomics and electron microscopy, we identified mitochondrial proteins that play important roles in the preservation of the mitochondrial ultrastructure and cholesterol-lowering properties of sericin...
October 8, 2018: Scientific Reports
Katarzyna Kornicka, Agnieszka Śmieszek, Jolanta Szłapka-Kosarzewska, Jennifer M Irwin Houston, Michael Roecken, Krzysztof Marycz
Endocrine disorders are becoming an increasing problem in both human and veterinary medicine. In recent years, more and more horses worldwide have been suffering from equine metabolic syndrome (EMS). This metabolic disorder is characterized by pathological obesity, hyperinsulinaemia, hyperglycaemia and insulin resistance. Although metabolic disorders, including diabetes, have been extensively studied, there are still no data on the molecular effects of EMS in horses. Thus, the aim of this study was to evaluate apoptosis, oxidative stress, autophagy and microRNA (miR) expression in multipotent intestinal epithelial stem cells (IECs) and pancreatic islets (PIs) isolated post mortem form healthy and EMS diagnosed horses...
October 8, 2018: International Journal of Molecular Sciences
Kivanc Görgülü, Kalliope N Diakopoulos, Jiaoyu Ai, Benjamin Schoeps, Derya Kabacaoglu, Angeliki-Faidra Karpathaki, Katrin J Ciecielski, Ezgi Kaya-Aksoy, Dietrich A Ruess, Alexandra Berninger, Marlena Kowalska, Marija Stevanovic, Sonja M Wörmann, Thomas Wartmann, Yue Zhao, Walter Halangk, Svetlana Voronina, Alexey Tepikin, Anna Melissa Schlitter, Katja Steiger, Anna Artati, Jerzy Adamski, Michaela Aichler, Axel Walch, Martin Jastroch, Götz Hartleben, Christos S Mantzoros, Wilko Weichert, Roland M Schmid, Stephan Herzig, Achim Krüger, Bruno Sainz, Marina Lesina, Hana Algül
BACKGROUND AND AIMS: Cells in pancreatic ductal adenocarcinoma (PDAC) undergo autophagy, but its effects vary with tumor stage and genetic factors. We investigated the consequences of varying levels of the autophagy related 5 (Atg5) protein on pancreatic tumor formation and progression. METHODS: We generated mice that express oncogenic Kras in primary pancreatic cancer cells and have homozygous disruption of Atg5 (A5;Kras) or heterozygous disruption of Atg5 (A5+/-;Kras), and compared them with mice with only oncogenic Kras (controls)...
October 5, 2018: Gastroenterology
Ben C King, Klaudia Kulak, Ulrika Krus, Rebecca Rosberg, Ewelina Golec, Katarzyna Wozniak, Maria F Gomez, Enming Zhang, David J O'Connell, Erik Renström, Anna M Blom
We show here that human pancreatic islets highly express C3, which is both secreted and present in the cytosol. Within isolated human islets, C3 expression correlates with type 2 diabetes (T2D) donor status, HbA1c, and inflammation. Islet C3 expression is also upregulated in several rodent diabetes models. C3 interacts with ATG16L1, which is essential for autophagy. Autophagy relieves cellular stresses faced by β cells during T2D and maintains cellular homeostasis. C3 knockout in clonal β cells impaired autophagy and led to increased apoptosis after exposure of cells to palmitic acid and IAPP...
October 1, 2018: Cell Metabolism
Kaylene Barrera, Albert Stanek, Kei Okochi, Zuzanna Niewiadomska, Cathy Mueller, Peiqi Ou, Devon John, Antonio E Alfonso, Scott Tenner, Chongmin Huan
Acute pancreatitis (AP) is an inflammatory disorder of pancreatic tissue initiated in injured acinar cells. Severe AP remains a significant challenge due to the lack of effective treatment. The widely-accepted autodigestion theory of AP is now facing challenges, since inhibiting protease activation has negligible effectiveness for AP treatment despite numerous efforts. Furthermore, accumulating evidence supports a new concept that malfunction of a self-protective mechanism, the unfolded protein response (UPR), is the driving force behind the pathogenesis of AP...
September 29, 2018: World Journal of Gastrointestinal Pathophysiology
Xinqun Li, Yeonju Lee, Ya'an Kang, Bingbing Dai, Mayrim Rios Perez, Michael Pratt, Eugene J Koay, Michael Kim, Rolf A Brekken, Jason B Fleming
Lumican is secreted by pancreatic stellate cells and inhibits cancer progression. Extracellular lumican inhibits cancer cell replication and restrains growth of early-stage pancreatic adenocarcinoma (PDAC) such that patients with tumors containing stromal lumican experience a three-fold longer survival after treatment. In the present study, patient tumor tissues, ex-vivo cultures of patient-derived xenografts (PDX), PDAC stellate and tumor cells were used to investigate whether hypoxia (1% O2 ) within the tumor microenvironment influences stromal lumican expression and secretion...
October 3, 2018: Cell Death and Differentiation
He Li, Hongying Chen, Ruli Li, Juanjuan Xin, Sisi Wu, Jie Lan, Kunyue Xue, Xue Li, Caili Zuo, Wei Jiang, Ling Zhu
Endoplasmic reticulum stress (ERS) is usually involved in tumor development and progression, and anticancer agents have recently been recognized to induce ERS. Cucurbitacin-I showed a potent anticancer action by inducing apoptosis through the inhibition of signal transducer and activator of transcription 3 pathway and triggering autophagic cell death. It is not known whether ERS mediates the cancer cell death induced by cucurbitacin-I. Here, we investigated the role of ERS in cucurbitacin-I-treated SKOV3 ovarian cancer cells and PANC-1 pancreatic cancer cells...
September 11, 2018: Journal of Cellular Biochemistry
Matthew D Smith, Simon Wilkinson
ER stress-mediated induction of a new vertebrate-specific autophagy cargo receptor, CCPG1 (cell-cycle progression gene 1), drives degradation of endoplasmic reticulum. CCPG1 acts via ATG8-family interaction and, non-canonically, via discrete interactions with FIP200. CCPG1 ameliorates ER stress in the exocrine pancreas. This has potential implications for inflammation and cancer, discussed here.
2018: Molecular & Cellular Oncology
Rajpal S Burmi, Elaina N Maginn, Hani Gabra, Euan A Stronach, Harpreet S Wasan
Pancreatic ductal adenocarcinoma (PDAC) progression and chemotherapy insensitivity have been associated with aberrant PI3K/mTOR/MEK signalling. However, cell death responses activated by inhibitors of these pathways can differ - contextually varying with tumour genetic background. Here, we demonstrate that combining the dual PI3K/mTOR inhibitor PF5212384 (PF384) and MEK inhibitor PD325901 (PD901) more effectively induces apoptosis compared with either agent alone, independent of KRAS mutational status in PDAC cell lines...
September 27, 2018: Cancer Biology & Therapy
Le Li, Gang Wang, Ji-Sheng Hu, Guang-Quan Zhang, Hong-Ze Chen, Yue Yuan, Yi-Long Li, Xin-Jian Lv, Feng-Yu Tian, Shang-Ha Pan, Xue-Wei Bai, Bei Sun
Chronic pancreatitis (CP) is described as a progressive fibro-inflammatory disorder of the exocrine disease, which eventually leads to damage of the gland. Excessive activation of pancreatic stellate cells (PSCs) is a critical participant in the initiation of CP. Autophagy is involved in multiple degeneration and inflammation in acute pancreatitis and CP. In our study, we report that retinoblastoma coiled coil protein 1 (RB1CC1) expression and the autophagic level are elevated in activated PSCs. RB1CC1 is positively correlated with pancreatic fibrogenesis in tissues and plasma of CP patients...
September 20, 2018: Cell Death & Disease
Kyota Aoyagi, Makoto Itakura, Toshiyuki Fukutomi, Chiyono Nishiwaki, Yoko Nakamichi, Seiji Torii, Tomohiko Makiyama, Akihiro Harada, Mica Ohara-Imaizumi
Dysfunctional mitochondria are observed in β-cells of diabetic patients, which are eventually removed by autophagy. VAMP7, a vesicular SNARE protein, regulates autophagosome formation to maintain mitochondrial homeostasis and control insulin secretion in pancreatic β-cells. However, its molecular mechanism is largely unknown. Here, we investigated the molecular mechanism of VAMP7-dependent autophagosome formation using VAMP7-deficient β-cells and β-cell derived Min6 cells. VAMP7 localised in Atg9a-resident vesicles of recycling endosomes (REs), which contributed to autophagosome formation, and interacted with Hrb, Syntaxin16, and SNAP-47...
September 12, 2018: Endocrinology
Debalina Bhattacharya, Mainak Mukhopadhyay, Maitree Bhattacharyya, Parimal Karmakar
Diabetes mellitus (DM) is an endocrine disorder. In coming decades it will be one of the leading causes of death globally. The key factors in the pathogenesis of diabetes are cellular injuries and disorders of energy metabolism leading to severe diabetic complications. Recent studies have confirmed that autophagy plays a pivotal role in diabetes and its complications. It has been observed that autophagy regulates the normal function of pancreatic β cells and insulin-target tissues, such as skeletal muscle, liver, and adipose tissue...
2018: EXCLI journal
Karlfried Groebe, Jing Cen, Domitille Schvartz, Ernest Sargsyan, Azazul Chowdhury, Kirsten Roomp, Reinhard Schneider, Anders Alderborn, Jean-Charles Sanchez, Peter Bergsten
In obese children with high circulating concentrations of free fatty acid palmitate, we have observed that insulin levels at fasting and in response to a glucose challenge were several times higher than in obese children with low concentrations of the fatty acid as well as in lean controls. Declining and even insufficient insulin levels were observed in obese adolescents with high levels of the fatty acid. In isolated human islets exposed to palmitate we have observed insulin hypersecretion after 2 days exposure...
October 3, 2018: Journal of Proteome Research
Xu Li, Meng Liang, Jianxin Jiang, Ruizhi He, Min Wang, Xingjun Guo, Ming Shen, Renyi Qin
Pancreatic cancer (PC) is highly resistant to current therapies; thus, there is an urgent need to develop new treatment strategies. The proteasome is crucially important for proteostasis, which is involved in cell proliferation and survival, making it an attractive therapeutic target in cancer. However, recent studies have indicated that bortezomib, a highly selective proteasome inhibitor, has limited effects in solid tumors including PC. Thus, more mechanistic insights into chemo-sensitization strategies for bortezomib are urgently needed...
2018: International Journal of Biological Sciences
Tao Ma, Wei Chen, Xiao Zhi, Hao Liu, Yue Zhou, Brayant Wei Chen, Liqiang Hu, Jian Shen, Xiaoxiao Zheng, Shufen Zhang, Bo Zhang, Haijun Li, Tingbo Liang
Gemcitabine is the cornerstone of pancreatic cancer treatment. Although effective in most patients, development of tumor resistance to gemcitabine can critically limit its efficacy. The mechanisms responsible for this phenomenon remain elusive, but evidence suggests that ubiquitin-specific peptidases (USPs) may be key regulators in cancer chemo-resistance. The present study aimed to investigate the role of USP9X in gemcitabine resistance using in vitro pancreatic cell lines and a mouse xenograft model. We found that the expression of USP9X in pancreatic cancer cells was positively correlated with gemcitabine resistance, and that inhibition of USP9X by WP1130 sensitized pancreatic cancer cells to gemcitabine...
November 1, 2018: Cancer Letters
Ahmad Fadhlurrahman Ahmad Hidayat, Chim Kei Chan, Jamaludin Mohamad, Habsah Abdul Kadir
ETHNOPHARMACOLOGICAL IMPORTANCE: Leptospermum flavescens has been used traditionally in Malaysia to treat various ailments such as constipation, hypertension, diabetes and cancer. AIM OF STUDY: To investigate the potential protective effects of L. flavescens in pancreatic β cells through inhibition of apoptosis and autophagy cell death mechanisms in in vitro and in vivo models. MATERIALS AND METHODS: L. flavescens leaves were extracted using solvent in increasing polarities: hexane, ethyl acetate, methanol and water...
November 15, 2018: Journal of Ethnopharmacology
María Inés Molejon, Mirna Swayden, Daniele Fanale, Jennifer Bintz, Odile Gayet, Philippe Soubeyran, Juan Iovanna
In this study, our aim is to assess the role played by autophagy and its inhibition in the different PDAC cellular compartments, and its involvement in chemo-resistance using primary human pancreatic cancer-derived cells (PCC) and Cancer Associated Fibroblasts (CAF). Autophagy flux, as measured by LC3-I and -II in the presence of Chloroquine, showed a variable level in PCC and CAFs. We found no correlation between autophagy level and degree of tumor differentiation. Association of Chloroquine with gemcitabine, 5FU, oxaliplatin, irinotecan and docetaxel revealed that its effect on survival is cell- and drug-dependent in vitro and in vivo ...
July 20, 2018: Oncotarget
Yu-Huei Liu, Yui-Ping Weng, Hsin-Ying Tsai, Chao-Jung Chen, Der-Yen Lee, Ching-Liang Hsieh, Yang-Chang Wu, Jung-Yaw Lin
BACKGROUND: Pancreatic cancer (PC) remains the leading cause of cancer mortality, with limited therapeutic targets, and alterations in endoplasmic reticulum (ER)-related proteostasis may be a potential target for therapy. The root bark of Paeonia suffruticosa has been shown to inhibit cancer growth and metastasis, although its impact on PC is unknown. PURPOSE: To ascertain the anti-cancer effects of P. suffruticosa on oncogenic functions of PC and determine the detailed molecular mechanisms...
July 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
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