Characterization of vectorial chloride transport pathways in the human pancreatic duct adenocarcinoma cell line HPAF

2003 ◽  
Vol 285 (2) ◽  
pp. C433-C445 ◽  
Author(s):  
Peying Fong ◽  
Barry E. Argent ◽  
William B. Guggino ◽  
Michael A. Gray

Pancreatic duct cells express a Ca2+-activated Cl- conductance (CaCC), upregulation of which may be beneficial to patients with cystic fibrosis. Here, we report that HPAF, a human pancreatic ductal adenocarcinoma cell line that expresses CaCC, develops into a high-resistance, anion-secreting epithelium. Mucosal ATP (50 μM) caused a fourfold increase in short-circuit current ( I sc), a hyperpolarization of transepithelial potential difference (from -4.9 ± 0.73 to -8.5 ± 0.84 mV), and a fall in resistance to less than one-half of resting values. The effects of ATP were inhibited by mucosal niflumic acid (100 μM), implicating an apical CaCC in the response. RT-PCR indicated expression of hClC-2, hClC-3, and hClC-5, but surprisingly not hCLCA-1 or hCLCA-2. K+ channel activity was necessary to maintain the ATP-stimulated I sc. Using a pharmacological approach, we found evidence for two types of K+ channels in the mucosal and serosal membranes of HPAF cells, one activated by chlorzoxazone (500 μM) and sensitive to clotrimazole (30 μM), as well as one blocked by clofilium (100 μM) but not chromanol 293B (5 μM). RT-PCR indicated expression of the Ca2+-activated K+ channel KCNN4, as well as the acid-sensitive, four transmembrane domain, two pore K+ channel, KCNK5 (hTASK-2). Western blot analysis verified the expression of CLC channels, as well as KCNK5. We conclude that HPAF will be a useful model system for studying channels pertinent to anion secretion in human pancreatic duct cells.

2002 ◽  
Vol 173 (1) ◽  
pp. 161-167 ◽  
Author(s):  
C Gil-Puig ◽  
M Blanco ◽  
T Garcia-Caballero ◽  
C Segura ◽  
R Perez-Fernandez

GH expression in mammary tumors has been related to the increase and spreading of cell proliferation. Using the MCF-7 human breast adenocarcinoma cell line, it has been demonstrated that autocrine GH-stimulated mammary carcinoma cell proliferation decreased the apoptosis rate and enhanced cell spreading. Surprisingly, no data are available about the presence of Pit-1 (the main pituitary regulator of GH) or GH expression in this cell line. Using RT-PCR, Western blot and immunohistochemistry, we have demonstrated the presence of both mRNA coding Pit-1 and GH as well as Pit-1 and GH protein in the MCF-7 cell line. These data could imply that Pit-1 may be an adequate target to inhibit breast cell proliferation.


1989 ◽  
Vol 120 (3_Suppl) ◽  
pp. S236 ◽  
Author(s):  
T. STROWITZKI ◽  
M. WIMBAUER ◽  
D. PFEIFFER ◽  
P. SCHEIDEL

2019 ◽  
Vol 16 (11) ◽  
pp. 1194-1201 ◽  
Author(s):  
Farhad Saravani ◽  
Ebrahim Saeedian Moghadam ◽  
Hafezeh Salehabadi ◽  
Seyednasser Ostad ◽  
Morteza Pirali Hamedani ◽  
...  

Background: The role of microtubules in cell division and signaling, intercellular transport, and mitosis has been well known. Hence, they have been targeted for several anti-cancer drugs. Methods: A series of 3-(alkylthio)-5,6-diphenyl-1,2,4-triazines were prepared and evaluated for their cytotoxic activities in vitro against three human cancer cell lines; human colon carcinoma cells HT-29, human breast adenocarcinoma cell line MCF-7, human Caucasian gastric adenocarcinoma cell line AGS as well as fibroblast cell line NIH-3T3 by MTT assay. Docking simulation was performed to insert these compounds into the crystal structure of tubulin at the colchicine binding site to determine a probable binding model. Compound 5d as the most active compound was selected for studying of microtubule disruption. Results: Compound 5d showed potent cytotoxic activity against all cell lines. The molecular modeling study revealed that some derivatives of triazine strongly bind to colchicine binding site. The tubulin polymerization assay kit showed that the cytotoxic activity of 5d may be related to inhibition of tubulin polymerization. Conclusion: The cytotoxicity and molecular modeling study of the synthesized compounds with their inhibition activity in tubulin polymerization demonstrate the potential of triazine derivatives for development of new anti-cancer agents.


Separations ◽  
2021 ◽  
Vol 8 (8) ◽  
pp. 114
Author(s):  
Mohammed Bourhia ◽  
Kaoutar Bouothmany ◽  
Hanane Bakrim ◽  
Safa Hadrach ◽  
Ahmad Mohammad Salamatullah ◽  
...  

Background: Citrullus colocynthis L. (C. colocynthis) is commonly known as colocynth. It belongs to the family Cucurbitaceae that is frequently used in alternative medicine in the north of Africa. The aim of the study: the present research was undertaken to investigate the chemical composition, antioxidant, antiproliferative, and antibacterial potentials of C. colocynthis seed extract. Material and methods: the chemical composition of C. colocynthis seed organic extract was characterized using gas chromatography/mass spectrometry (GC-MS). The antioxidant property was carried out using both β-carotene bleaching and DPPH assays. The antibacterial effect was effectuated using the agar disc diffusion method. The antiproliferative activity vs. human colorectal adenocarcinoma cell line (HT-29) and human breast adenocarcinoma cell line (MDA MB 231) were carried by WST-1 test. The chemical analysis showed the presence of interesting potentially bioactive compounds. The studied plant extract exhibited antioxidant potential with IC50 value of 2. 22 mg/mL (β-carotene bleaching) and 8.98 ± 0.619 mg/mL (DPPH). Concerning the antiproliferative activity, the seed extract was effective in MDA-MB-231 and HT-29 cancer cells with IC50 values 86.89 ± 3.395 and 242.1 ± 17.9 μg/mL, respectively, whilst the extract of Citrullus colocynthis seeds was non-toxic in healthy human dermal fibroblasts. Regarding the antibacterial test, the extract was effective in Gram-positive bacteria only. Conclusion: The outcome of this research indicated that the extracts from C. colocynthis seeds may compose a promising source with interesting compounds that can be used to fight cancer, free radicals damage, and bacterial infections.


2009 ◽  
Vol 29 (4) ◽  
pp. 308-316 ◽  
Author(s):  
Renata Matuo ◽  
Fabrício Garmus Sousa ◽  
Alexandre E. Escargueil ◽  
Ivana Grivicich ◽  
Daniel Garcia-Santos ◽  
...  

2009 ◽  
Vol 96 (3) ◽  
pp. 536a-537a
Author(s):  
Viktoria Venglovecz ◽  
Peter Hegyi ◽  
Zoltan Rakonczay ◽  
Barry Argent ◽  
Michael A. Gray

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