scholarly journals Synergism between SLC6A14 blockade and gemcitabine in pancreactic cancer: a 1H-NMR-based metabolomic study in pancreatic cancer cells

2020 ◽  
Vol 477 (10) ◽  
pp. 1923-1937 ◽  
Author(s):  
Aimin Cai ◽  
Hailun Zheng ◽  
Zhiwei Chen ◽  
Xinlu Lin ◽  
Chen Li ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Amino Acid ◽  
Cancer Cells ◽  
1H Nmr ◽  
Metabolic Pathways ◽  
Pancreatic Cancer Cell Line ◽  
Metabolite Profile ◽  
Human Pancreatic Cancer ◽  
Combination Regimen ◽  
Pancreatic Cancer Cells

Gemcitabine is the first-line chemotherapy for pancreatic cancer. To overcome the often-acquired gemcitabine resistance, other drugs are used in combination with gemcitabine. It is well-known that cancer cells reprogram cellular metabolism, coupled with the up-regulation of selective nutrient transporters to feed into the altered metabolic pathways. Our previous studies have demonstrated that the amino acid transporter SLC6A14 is markedly up-regulated in pancreatic cancer and that it is a viable therapeutic target. α-Methyltryptophan (α-MT) is a blocker of SLC6A14 and is effective against pancreatic cancer in vitro and in vivo. In the present study, we tested the hypothesis that α-MT could synergize with gemcitabine in the treatment of pancreatic cancer. We investigated the effects of combination of α-MT and gemcitabine on proliferation, migration, and apoptosis in a human pancreatic cancer cell line, and examined the underlying mechanisms using 1H-NMR-based metabolomic analysis. These studies examined the intracellular metabolite profile and the extracellular metabolite profile separately. Combination of α-MT with gemcitabine elicited marked changes in a wide variety of metabolic pathways, particularly amino acid metabolism with notable alterations in pathways involving tryptophan, branched-chain amino acids, ketone bodies, and membrane phospholipids. The metabolomic profiles of untreated control cells and cells treated with gemcitabine or α-MT were distinctly separable, and the combination regimen showed a certain extent of overlap with the individual α-MT and gemcitabine groups. This represents the first study detailing the metabolomic basis of the anticancer efficacy of gemcitabine, α-MT and their combination.

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

Cancers ◽  
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.

Possible role of autophagy inhibition in hypoxia-induced chemoresistance of pancreatic cancer cells.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 224-224 ◽  
Author(s):  
Yoon Ho Ko ◽  
Young-Seok Cho ◽  
Hye Sung Won ◽  
Eun Kyoung Jeon ◽  
Young Seon Hong
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Western Blotting ◽  
Pancreatic Cancer Cell Line ◽  
Cancer Cell Line ◽  
Hypoxic Condition ◽  
Human Pancreatic Cancer ◽  
Pancreatic Cancer Cells ◽  
Autophagy Inhibition

224 Background: Autophagy is a catabolic process and provides metabolic support for the cell by degradation of intracellular macromolecules. Various types of stress, including hypoxia, activate autophagy. Recent studies have suggested that hypoxia has been shown to associate with resistance to chemotherapy and radiation therapy and hence poor prognosis in pancreatic cancer. This study investigated the role of autophagy in the treatment of pancreatic cancer with gemcitabine under hypoxic condition. Methods: To evaluate the role of autophagy inhibition in hypoxia-induced chemoresistance, BxPC-3 human pancreatic cancer cell line was used under normoxic and hypoxic conditions.We evaluated the extent of LC3-II, as an autophagosome marker, induced by gemcitabine, by western blotting to measure the hypoxia- or chemotherapy- induced autophagy. We then examined the effects of gemcitabine on induction of apoptosis under normoxic and hypoxic conditions. Next, to determine the effect of 3-MA, a known inhibitor of autophagy, on overcoming hypoxia-induced chemoresistance, the MTS assay and flow cytometry were performed. Results: Compared with normoxia, gemcitabine-induced cell death under hypoxia was significantly decreased, as a result of the reduced apoptosis. Western blotting analysis demonstrated that LC3-II was increased under hypoxia, compared with normoxia.However, we found that 3-MA can enhance the growth inhibition and apoptotic effect of gemcitabine, even under hypoxia. These findings mean that autophagy mediates the chemoresistance under hypoxia. Conclusions: Activated autophagy plays a role in hypoxia-induced chemoresistance of pancreatic cancer cells. These findings may have important implications for future therapeutic strategies using gemcitabine against pancreatic cancer.

scholarly journals Ancistrolikokines E–H and related 5,8′-coupled naphthylisoquinoline alkaloids from the Congolese lianaAncistrocladus likokowith antiausterity activities against PANC-1 human pancreatic cancer cells

RSC Advances ◽  
2017 ◽  
Vol 7 (85) ◽  
pp. 53740-53751 ◽  
Author(s):  
Shaimaa Fayez ◽  
Doris Feineis ◽  
Virima Mudogo ◽  
Suresh Awale ◽  
Gerhard Bringmann
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Metabolite Profile ◽  
Striking Feature ◽  
Human Pancreatic Cancer ◽  
Exclusive Production ◽  
Pancreatic Cancer Cells ◽  
Naphthylisoquinoline Alkaloids

A striking feature of the metabolite profile ofAncistrocladus likoko(Ancistrocladaceae) is the exclusive production of 5,8′-linked naphthylisoquinoline alkaloids with strong activities against pancreatic cancer cells.

scholarly journals Activation of GLP-1 receptor enhances the chemosensitivity of pancreatic cancer cells

2020 ◽  
Vol 64 (2) ◽  
pp. 103-113
Author(s):  
He-jun Zhao ◽  
Xia Jiang ◽  
Li-juan Hu ◽  
Lei Yang ◽  
Lian-dong Deng ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Pancreatic Cancer Cell ◽  
Pancreatic Cancer Cell Line ◽  
Cancer Cell Line ◽  
Human Pancreatic Cancer ◽  
Pancreatic Cancer Cells

This study aimed to determine whether and how the glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide affects the chemoresistance and chemosensitivity of pancreatic cancer cells to gemcitabine in vitro and in vivo. The GLP-1R and protein kinase A (PKA) levels were compared between the human pancreatic cancer cell line PANC-1 and the gemcitabine-resistant cell line PANC-GR. The in vitro effects of liraglutide on the cell proliferation and apoptosis as well as the nuclear factor-kappa B NF-κB expression levels of PANC-GR cells were evaluated. In addition, a mouse xenograft model of human pancreatic cancer was established by s.c. injection of PANC-1 cells, and the effects of liraglutide on the chemosensitivity were evaluated in vitro and in vivo. In contrast to PANC-1 cells, PANC-GR cells exhibited lower expression levels of GLP-1R and PKA. Incubation with liraglutide dose dependently inhibited the growth, promoted the apoptosis, and increased the expression of GLP-1R and PKA of PANC-GR cells. Similar effects of liraglutide were observed in another human pancreatic cancer cell line MiaPaCa-2/MiaPaCa-2-GR. Either the GLP-1R antagonist Ex-9, the PKA inhibitor H89, or the NF-κB activator lipopolysaccharide (LPS) could abolish the antiproliferative and proapoptotic activities of liraglutide. Additionally, each of these agents could reverse the expression of NF-κB and ABCG2, which was decreased by liraglutide treatment. Furthermore, liraglutide treatment increased the chemosensitivity of pancreatic cancer cells to gemcitabine, as evidenced by in vitro and in vivo experiments. Thus, GLP-1R agonists are safe and beneficial for patients complicated with pancreatic cancer and diabetes, especially for gemcitabine-resistant pancreatic cancer.

Cholecystokinin receptors and PANC-1 human pancreatic cancer cells

1993 ◽  
Vol 265 (1) ◽  
pp. G149-G155 ◽  
Author(s):  
J. P. Smith ◽  
C. A. Rickabaugh ◽  
P. J. McLaughlin ◽  
I. S. Zagon
Keyword(s):  
Pancreatic Cancer ◽  
Receptor Antagonist ◽  
Cancer Cells ◽  
Binding Capacity ◽  
Pancreatic Cancer Cell Line ◽  
Human Pancreatic Cancer ◽  
Scatchard Analysis ◽  
Binding Studies ◽  
Cck Receptors ◽  
Pancreatic Cancer Cells

The gastrointestinal peptide cholecystokinin (CCK) has been shown to stimulate growth of human pancreatic adenocarcinoma in vitro and in vivo, although CCK receptors have not been identified in pancreatic cancer cells. The purpose of this study was to characterize the CCK receptors in pancreatic cancer cells and to correlate the receptor binding studies with the trophic action of CCK agonists and antagonists. With the use of homogenates of PANC-1 human pancreatic cancer cell line grown in culture, the binding of 125I-labeled CCK octapeptide (125I-CCK-8) was examined under various conditions to characterize the CCK receptor. Specific and saturable binding of 125I-CCK-8 was detected in PANC-1 cells; data were consistent with a single binding site. Scatchard analysis yielded a binding affinity [dissociation constant (Kd)] of 2.8 nM and a binding capacity of 26 fmol/mg protein. Binding was dependent on protein concentration, time, temperature, the presence of protease inhibitors, and pH and was sensitive to Na+, K+, Mg2+, and ethylene glycolbis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. Competition experiments indicated that L-365,260, a selective CCK-B (gastrin) receptor antagonist, was the most potent displacer of 125I-CCK-8, and no significant displacement of binding was found with the selective CCK-A receptor antagonist. Growth of PANC-1 cells in culture was stimulated by CCK at a concentration consistent with the Kd, and CCK-stimulated growth was inhibited by the CCK-B receptor antagonist (L-365,260) not the CCK-A receptor antagonist (L-364,718).(ABSTRACT TRUNCATED AT 250 WORDS)

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

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

scholarly journals Patterns and Relevance of Langerhans Islet Invasion in Pancreatic Cancer

Cancers ◽  
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.

Ursolic acid promotes apoptosis, autophagy, and chemosensitivity in gemcitabine‐resistant human pancreatic cancer cells

2020 ◽  
Vol 34 (8) ◽  
pp. 2053-2066 ◽  
Author(s):  
Ji‐Hua Lin ◽  
Sheng‐Yi Chen ◽  
Chi‐Cheng Lu ◽  
Jer‐An Lin ◽  
Gow‐Chin Yen
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Ursolic Acid ◽  
Human Pancreatic Cancer ◽  
Pancreatic Cancer Cells

scholarly journals Up-Regulation of MSX2 Enhances the Malignant Phenotype and Is Associated with Twist 1 Expression in Human Pancreatic Cancer Cells

2008 ◽  
Vol 172 (4) ◽  
pp. 926-939 ◽  
Author(s):  
Kennichi Satoh ◽  
Shin Hamada ◽  
Kenji Kimura ◽  
Atsushi Kanno ◽  
Morihisa Hirota ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Human Pancreatic Cancer ◽  
Malignant Phenotype ◽  
Pancreatic Cancer Cells ◽  
Twist 1
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