Wound Healing, Anti-pancreatic Cancer, and α-amylase Inhibitory Potentials of the Edible Mushroom, Metacordyceps neogunnii

Metacordyceps neogunnii is an edible mushroom that has been previously known as Cordyceps gunnii. Recently, it has been proven that Metacordyceps neogunnii differs from similar species by having longer asci and wider ascospores and is phylogenetically distinct to related species. Few studies are available to describe bioactivities exerted by Metacordyceps neogunnii extracts which is insufficient to evaluate the potency of this mushroom. Therefore, the current work was conducted to evaluate the in vitro α-Amylase inhibitory ability, wound healing, and anti-human pancreatic cancer activities of Metacordyceps neogunnii 80% methanolic extract. M. neogunnii extract showed no effect on human cancer pancreatic cell line (Paca2). However, the same extract exhibited slight wound healing effect. On the other hand, M. neogunnii extract exhibited good α-amylase inhibitory activity that reached 69.3±0.78%, and IC50 of 32.38±4.0.

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The role of Notch3 signaling pathway in pancreatic cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.21049 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 21049-21049 ◽

Cited By ~ 3

Author(s):

T. Dang ◽

k. Vo ◽

K. Washington ◽

J. Berlin

Keyword(s):

Pancreatic Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Pancreas Cancer ◽

Human Cancer ◽

Pancreatic Cancer Cell Line ◽

Pancreatic Tissue ◽

Tissue Array ◽

Pancreatic Cell

21049 Background: Given the extremely poor prognosis of patients diagnosed with pancreatic cancer, identifying new targets for therapeutic intervention is crucial in improving clinical outcome. Existing data support a role for Notch3 pathway in human cancer, pancreas cancer in specific and in normal pancreas development. Method: We developed a pancreatic tissue array. An antibody targeting the extracellular domain of Notch3 was used to evaluate expression levels, grading from 0 to 4+ to determine the prevalence of Notch3 in pancreatic cancer. Notch3 expression was used to correlate with clinical data (IRB approved). Using small interfering RNA (siRNA) we tested the downstream effects of Notch3 in pancreatic cancer cell line BxP3 in vitro. Furthermore, to study pharmacologic inhibition of Notch3 processing and activation we exposed Panc-1, HPAF II and BxP3 pancreas cancer cell lines to γ-secretase inhibitors (previously demonstrated to block upstream of Notch3 thereby inhibiting Notch3). Results: Strong staining (+2 or greater) for Notch3 was seen in 50 of 72 (69%) resected specimens. No correlation with survival or tumor grade was seen. Using siRNA, we demonstrated that inhibiting Notch3 downregulated the antiapoptotic protein Bcl-xL but not Bcl-2. When γ-secretase inhibitors (GSI and L-685,458) were used, the previously mentioned pancreatic cell lines demonstrated reduction in proliferation rates. Conclusion: Notch3 overexpression is common in pancreas cancer. While Notch 3 expression does not clearly correlate with survival, our in vitro data suggest that Notch3 affects apoptotic pathways and may represent a potential target for intervention in patients with pancreatic cancer. No significant financial relationships to disclose.

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Synergistic Effect of the Combination of Polyphenols with Gemcitabineon Pancreatic Cancer Cell line AsPC-1

Journal of Pharmaceutical Research ◽

10.33140/jpr/02/01/00004 ◽

2017 ◽

Vol 2 (1) ◽

Keyword(s):

Pancreatic Cancer ◽

Cell Line ◽

Efflux Pump ◽

Flow Cytometric Analysis ◽

Pancreatic Cancer Cell Line ◽

Cancer Cell Line ◽

Human Pancreatic Cancer ◽

Pancreatic Cell ◽

Pancreatic Cancer Cells

In our diet, polyphenols are micronutrients with an important role in the prevention of degenerative diseases such as cancer and cardiovascular diseases. Particularly, Pancreatic cancer is one of the most aggressive cancers, with only about 5% of patients surviving 5 years past the initial diagnosis. Despite advances with current chemotherapy combinations, overall survival outcomes are still require novel therapeutic approaches. Here, we examined the efficacy of combined treatments of polyphenols and gemcitabine the standard of treatment for patients with metastatic pancreatic cancer in human pancreatic cancer cells. For that purpose, the pro-apoptic effects of gemcitabine were studied on the human pancreatic cell line AsPC1 in presence or absence of several polyphenols, in order to evaluate if they latter are able to potentialize gemcitabine cytotoxicity. Our study aims to investigate the implication of MDR1 (multidrug transporter)in resistance to gemcitabine and if the studied polyphenol could target this drug efflux pump in AsPC-1 cells by flow cytometric analysis. We observed that 5µg/ml gemcitabine in combination with 15 µg/ml of selected polyphenol (Catechin, Quercetin, Bergamottin, Rhamnetin) was more effective than gemcitabine alone, by increased in the percentage of dead cells up to 60%. Morever our results demonstrated that some polyphenols (Quercetin) inhibit the efflux activity of MDR1. Our study in vitro suggests therefore that chemotherapy with gemcitabine might be significantly increased upon combination with specific polyphenol. In conclusion, polyphenols may be promising agents for novel combination therapy since they potentialize the cytotoxic activity of gemcitabine to eradicate pancreatic cancer and therefore the cellular resistance.

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Serum Neurotensin in Human Pancreatic Cancer

Tumori Journal ◽

10.1177/030089169608200616 ◽

1996 ◽

Vol 82 (6) ◽

pp. 592-595 ◽

Cited By ~ 6

Author(s):

Tamara Meggiato ◽

Chiara Ferrara ◽

Giovanna Tessari ◽

Mario Plebani ◽

Massimo De Paoli ◽

...

Keyword(s):

Pancreatic Cancer ◽

Chronic Pancreatitis ◽

Cancer Patients ◽

Human Cancer ◽

Stage Iv ◽

Serum Levels ◽

Human Pancreatic Cancer ◽

Human Cancer Cells ◽

Control Subjects

The role of neurotensin as a physiologic regulator of exocrine pancreatic secretion is known, but the hormone has only recently been recognized as important mitogen in vitro for human cancer cells. The aim of this study was to evaluate the variations of serum levels of neurotensin in pancreatic cancer. We studied 58 patients: 13 control subjects, 20 pancreatic cancer patients, 11 chronic pancreatitis patients, and 14 cases of extrapancreatic disease. No differences were found between serum values of neurotensin in pancreatic cancer and control subjects or extrapancreatic disease. Significantly higher values were detected in chronic pancreatitis than in pancreatic cancer patients ( P <0.04). In chronic pancreatitis patients, the serum levels of neurotensin were correlated with serum amylase ( r = 0.95, P <0.01). Lower levels of neurotensin were found in stage IV pancreatic cancer than in stages I-II ( t = 1.82, P <0.04) and in grade II than in grade I ( t = 2.21, P <0.02). Significant correlations were found between serum levels of neurotensin and two indices of nutrition: albumin ( r = 0.60, P <0.05) and the percentage reduction in body weight (Z = 2.20, P <0.02). No correlations were found between serum levels of the hormone and size of the neoplasm or the survival of patients. We can conclude that the serum variations of neurotensin do not seem to be related to the progression of human pancreatic cancer. The variation of serum levels of the hormone may be linked to a poor nutritional status of the patient.

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Restriction of extracellular lipids renders pancreatic cancer dependent on autophagy

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-02231-y ◽

2022 ◽

Vol 41 (1) ◽

Author(s):

Maria Saliakoura ◽

Matteo Rossi Sebastiano ◽

Ioanna Nikdima ◽

Chiara Pozzato ◽

Georgia Konstantinidou

Keyword(s):

Pancreatic Cancer ◽

Fatty Acids ◽

Cancer Cell ◽

Human Cancer ◽

Human Pancreatic Cancer ◽

Ductal Adenocarcinoma ◽

Extracellular Lipid ◽

Autophagy Inhibition

Abstract Background KRAS is the predominant oncogene mutated in pancreatic ductal adenocarcinoma (PDAC), the fourth cause of cancer-related deaths worldwide. Mutant KRAS-driven tumors are metabolically programmed to support their growth and survival, which can be used to identify metabolic vulnerabilities. In the present study, we aimed to understand the role of extracellularly derived fatty acids in KRAS-driven pancreatic cancer. Methods To assess the dependence of PDAC cells on extracellular fatty acids we employed delipidated serum or RNAi-mediated suppression of ACSL3 (to inhibit the activation and cellular retention of extracellular fatty acids) followed by cell proliferation assays, qPCR, apoptosis assays, immunoblots and fluorescence microscopy experiments. To assess autophagy in vivo, we employed the KrasG12D/+;p53flox/flox;Pdx1-CreERT2 (KPC) mice crossed with Acsl3 knockout mice, and to assess the efficacy of the combination therapy of ACSL3 and autophagy inhibition we used xenografted human cancer cell-derived tumors in immunocompromised mice. Results Here we show that depletion of extracellularly derived lipids either by serum lipid restriction or suppression of ACSL3, triggers autophagy, a process that protects PDAC cells from the reduction of bioenergetic intermediates. Combined extracellular lipid deprivation and autophagy inhibition exhibits anti-proliferative and pro-apoptotic effects against PDAC cell lines in vitro and promotes suppression of xenografted human pancreatic cancer cell-derived tumors in mice. Therefore, we propose lipid deprivation and autophagy blockade as a potential co-targeting strategy for PDAC treatment. Conclusions Our work unravels a central role of extracellular lipid supply in ensuring fatty acid provision in cancer cells, unmasking a previously unappreciated metabolic vulnerability of PDAC cells.

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In Vitro and In Vivo Antitumor Efficacy of Docetaxel and Sorafenib Combination in Human Pancreatic Cancer Cells

Current Cancer Drug Targets ◽

10.2174/1568210204916170096 ◽

2010 ◽

Vol 999 (999) ◽

pp. 1-11

Author(s):

P. Ulivi ◽

C. Arienti ◽

W. Zoli ◽

M. Scarsella ◽

S. Carloni ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Cells ◽

Antitumor Efficacy ◽

Human Pancreatic Cancer ◽

Pancreatic Cancer Cells

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Oncogene APOL1 promotes proliferation and inhibits apoptosis via activating NOTCH1 signaling pathway in pancreatic cancer

Cell Death and Disease ◽

10.1038/s41419-021-03985-1 ◽

2021 ◽

Vol 12 (8) ◽

Author(s):

Jiewei Lin ◽

Zhiwei Xu ◽

Junjie Xie ◽

Xiaxing Deng ◽

Lingxi Jiang ◽

...

Keyword(s):

Pancreatic Cancer ◽

Signaling Pathway ◽

Density Lipoprotein ◽

Human Pancreatic Cancer ◽

Luciferase Reporter ◽

Notch1 Signaling ◽

In Vivo Experiments ◽

Notch1 Signaling Pathway

AbstractAPOL1 encodes a secreted high-density lipoprotein, which has been considered as an aberrantly expressed gene in multiple cancers. Nevertheless, the role of APOL1 in the regulatory mechanisms of pancreatic cancer remains unknown and should be explored. We identified APOL1 was abnormally elevated in human pancreatic cancer tissues compared with that in adjacent tissues and was associated with poor prognosis. The effects of APOL1 in PC cell proliferation, cell cycle, and apoptosis was verified via functional in vitro and in vivo experiments. The results showed that knockdown of APOL1 significantly inhibited the proliferation and promoted apoptosis of pancreatic cancer. In addition, we identified APOL1 could be a regulator of NOTCH1 signaling pathway using bioinformatics tools, qRT-PCR, dual-luciferase reporter assay, and western blotting. In summary, APOL1 could function as an oncogene to promote proliferation and inhibit apoptosis through activating NOTCH1 signaling pathway expression in pancreatic cancer; therefore, it may act as a novel therapeutic target for pancreatic cancer.

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Cyathus striatus Extract Induces Apoptosis in Human Pancreatic Cancer Cells and Inhibits Xenograft Tumor Growth In Vivo

Cancers ◽

10.3390/cancers13092017 ◽

2021 ◽

Vol 13 (9) ◽

pp. 2017

Author(s):

Lital Sharvit ◽

Rinat Bar-Shalom ◽

Naiel Azzam ◽

Yaniv Yechiel ◽

Solomon Wasser ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Cells ◽

Pancreatic Cancer Cell Line ◽

Cancer Cell Line ◽

Culture Liquid ◽

Human Pancreatic Cancer ◽

P53 Signaling ◽

Pancreatic Cancer Cells

Pancreatic cancer is a highly lethal disease with limited options for effective therapy and the lowest survival rate of all cancer forms. Therefore, a new, effective strategy for cancer treatment is in need. Previously, we found that a culture liquid extract of Cyathus striatus (CS) has a potent antitumor activity. In the present study, we aimed to investigate the effects of Cyathus striatus extract (CSE) on the growth of pancreatic cancer cells, both in vitro and in vivo. The proliferation assay (XTT), cell cycle analysis, Annexin/PI staining and TUNEL assay confirmed the inhibition of cell growth and induction of apoptosis by CSE. A Western blot analysis demonstrated the involvement of both the extrinsic and intrinsic apoptosis pathways. In addition, a RNAseq analysis revealed the involvement of the MAPK and P53 signaling pathways and pointed toward endoplasmic reticulum stress induced apoptosis. The anticancer activity of the CSE was also demonstrated in mice harboring pancreatic cancer cell line-derived tumor xenografts when CSE was given for 5 weeks by weekly IV injections. Our findings suggest that CSE could potentially be useful as a new strategy for treating pancreatic cancer.

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Patterns and Relevance of Langerhans Islet Invasion in Pancreatic Cancer

Cancers ◽

10.3390/cancers13020249 ◽

2021 ◽

Vol 13 (2) ◽

pp. 249

Author(s):

Ruediger Goess ◽

Ayse Ceren Mutgan ◽

Umut Çalışan ◽

Yusuf Ceyhun Erdoğan ◽

Lei Ren ◽

...

Keyword(s):

Diabetes Mellitus ◽

Pancreatic Cancer ◽

Cancer Cells ◽

Tumor Cells ◽

Islet Cells ◽

Human Pancreatic Cancer ◽

Type I ◽

Type Iv ◽

Pancreatic Cancer Cells

Background: Pancreatic cancer‐associated diabetes mellitus (PC‐DM) is present in most patients with pancreatic cancer, but its pathogenesis remains poorly understood. Therefore, we aimed to characterize tumor infiltration in Langerhans islets in pancreatic cancer and determine its clinical relevance. Methods: Langerhans islet invasion was systematically analyzed in 68 patientswith pancreatic ductal adenocarcinoma (PDAC) using histopathological examination and 3D in vitro migration assays were performed to assess chemoattraction of pancreatic cancer cells to isletcells. Results: Langerhans islet invasion was present in all patients. We found four different patterns of islet invasion: (Type I) peri‐insular invasion with tumor cells directly touching the boundary, but not penetrating the islet; (Type II) endo‐insular invasion with tumor cells inside the round islet; (Type III) distorted islet structure with complete loss of the round islet morphology; and (Type IV)adjacent cancer and islet cells with solitary islet cells encountered adjacent to cancer cells. Pancreatic cancer cells did not exhibit any chemoattraction to islet cells in 3D assays in vitro. Further, there was no clinical correlation of islet invasion using the novel Islet Invasion Severity Score (IISS), which includes all invasion patterns with the occurrence of diabetes mellitus. However, Type IV islet invasion was related to worsened overall survival in our cohort. Conclusions: We systematically analyzed, for the first time, islet invasion in human pancreatic cancer. Four different main patterns of islet invasion were identified. Diabetes mellitus was not related to islet invasion. However, moreresearch on this prevailing feature of pancreatic cancer is needed to better understand underlying principles.

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Anti-austeric Activity of Phenolic Constituents of Seeds of Arctium lappa

Natural Product Communications ◽

10.1177/1934578x1300800414 ◽

2013 ◽

Vol 8 (4) ◽

pp. 1934578X1300800 ◽

Cited By ~ 4

Author(s):

Yasuhiro Tezuka ◽

Keiichi Yamamoto ◽

Suresh Awale ◽

Feng Li ◽

Satoshi Yomoda ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cytotoxic Activity ◽

Chlorogenic Acid ◽

Human Pancreatic Cancer ◽

Arctium Lappa ◽

Dicaffeoylquinic Acid ◽

Phenolic Constituents ◽

Pure Compounds ◽

F 14

From seeds of Arctium lappa L. (Asteraceae) we obtained arctigenin (1), arctiin (2), chlorogenic acid (3), 4,5-dicaffeoylquinic acid (4), 3,5-dicaffeoylquinic acid (5), 3,4-dicaffeoylquinic acid (6), matairesinol (11), isolappaol A (12), lappaol F (14), and lappaol B (15), together with 1:1 mixtures of isolappaol C (7) and lappaol C (8), arctignan E (9) and arctignan D (10), and 12 and lappaol A (13), while 3,3′,4′-tri- O-demethylarctigenin (16), 3,3′-di- O-demethyl-4′-dehydroxyarctigenin (17), and 3- O-demethylarctigenin (18) were obtained by anaerobic microbiological metabolism of 1. Then, we evaluated the in vitro preferential cytotoxic activity of these pure compounds and 1:1 mixtures, together with enterodiol (19) and enterolactone (20), against human pancreatic cancer PANC-1 cells in nutrient-deprived medium (NDM). Among them, 1 and 18 showed potent activity, with PC50 values of 1.75 and 4.38 μ M, respectively, while 11, 15, and 17 showed mild activity with PC50 values of 31.1, 30.9, and 38.7 μ/M, respectively. By comparing their structures and PC50 values, the following structural moieties could be concluded to be important for the preferential cytotoxicity of 1: 1) the 3-hydroxy-4-methoxyphenyl group at the 2-position on the γ-butyrolactone ring, 2) the less polar substituent at the 3-position on the γ-butyrolactone ring, and 3) the γ-butyrolactone ring.

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