scholarly journals NS-11021 Modulates Cancer-Associated Processes Independently of BK Channels in Melanoma and Pancreatic Duct Adenocarcinoma Cell Lines

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6144
Author(s):  
Alessia Remigante ◽  
Paolo Zuccolini ◽  
Raffaella Barbieri ◽  
Loretta Ferrera ◽  
Rossana Morabito ◽  
...  

Potassium channels have emerged as regulators of carcinogenesis, thus introducing possible new therapeutic strategies in the fight against cancer. In particular, the large-conductance Ca2+-activated K+ channel, often referred to as BK channel, is involved in several cancer-associated processes. Here, we investigated the effects of different BK activators, NS-11021, NS-19504, and BMS-191011, in IGR39 (primary melanoma cell line) and Panc-1 (primary pancreatic duct carcinoma cell line), highly expressing the channel, and in IGR37 (metastatic melanoma cell line) that barely express BK. Our data showed that NS-11021 and NS-19504 potently activated BK channels in IGR39 and Panc-1 cells, while no effect on channel activation was detected in IGR37 cells. On the contrary, BK channel activator BMS-191011 was less effective. However, only NS-11021 showed significant effects in cancer-associated processes, such as cell survival, migration, and proliferation in these cancer cell lines. Moreover, NS-11021 led to an increase of intracellular Ca2+ concentration, independent of BK channel activation, thus complicating any interpretation of its role in the regulation of cancer-associated mechanisms. Overall, we conclude that the activation of the BK channel by itself is not sufficient to produce beneficial anti-cancer effects in the melanoma and PDAC cell lines examined. Importantly, our results raise an alarm flag regarding the use of presumably specific BK channel openers as anti-cancer agents.

1985 ◽  
Vol 231 (2) ◽  
pp. 309-313 ◽  
Author(s):  
G Opdenakker ◽  
A Billiau ◽  
G Volckaert ◽  
P de Somer

A labelled cDNA clone was used in DNA-RNA hybridization on nitrocellulose filter paper (dot-blot technique) to detect and quantify mRNA for endogenous tissue plasminogen activator (PA) in cell extracts and samples of RNA purification runs. Although, for detection purposes, the assay was less sensitive than translation in Xenopus oocytes, it was at least as reliable and much more convenient for the purpose of quantitative determination. In particular, the technique was used to study the kinetics of PA mRNA formation in a human melanoma cell line (Bowes) after exposure to the tumour promoter 12-O-tetradecanoylphorbol 13-acetate (TPA). Incubation of the cells with TPA resulted in a 15-20-fold increase in cellular PA mRNA content. The effect was time- and dose-dependent: the increase in PA-specific mRNA was clearly visible as early as 4 h after initiation of TPA treatment in Bowes cells. It was blocked completely by pretreatment of the cells with actinomycin D, indicating that TPA caused enhancement of synthesis of PA mRNA rather than inhibition of PA mRNA degradation. The use of the nitrocellulose dot-blot technique also revealed that two non-human cell lines produce mRNAs which cross-react with the human PA mRNA, namely the mouse melanoma cell line B16 and the rat brain-tumour cell line, RT4-71-1. TPA was found to exert similar stimulatory effects on the synthesis of mRNAs in these cell lines as in Bowes cells.


Blood ◽  
1992 ◽  
Vol 80 (2) ◽  
pp. 374-381 ◽  
Author(s):  
AM Turner ◽  
KM Zsebo ◽  
F Martin ◽  
FW Jacobsen ◽  
LG Bennett ◽  
...  

Abstract Human stem cell factor (SCF) acts in the presence of other growth factors to stimulate the growth of primitive hematopoietic progenitor cells. These effects are performed by activation of the SCF receptor, c- kit. Because of the potential use of SCF in patients undergoing chemotherapy and bone marrow transplantation, the effect of SCF on nonhematopoietic tumors requires investigation. To determine whether human tumor cell lines display c-kit receptors, we performed binding experiments with 125I-SCF on a breast carcinoma cell line (Du4475), a gastric carcinoma cell line (KATO III), a melanoma cell line (HTT144), as well as two small cell lung carcinoma cell lines (H69 and H128). The biologic effect of SCF on tumor cell lines was assessed by its ability to stimulate tritiated thymidine uptake and to enhance colony growth in methylcellulose. The breast carcinoma cell line, Du4475, as well as two small cell lung carcinoma cell lines, H69 and H128, exhibit high- affinity c-kit receptors with approximate binding affinities of 40, 100, and 90 pmol/L, respectively. The number of high-affinity receptors per cell ranged from 700 to 9,500. The gastric carcinoma cell line, as well as the melanoma cell line, showed trace binding of 125I-SCF. In the presence of SCF alone, or in combination with granulocyte- macrophage colony-stimulating factor or interleukin-3, there was less than a 17% increase in the colony growth of Du4475, H69, or H128 cell lines. Postulating that the lack of growth response could be secondary to endogenous SCF production by the tumor cell lines, we used an RNAse protection assay to determine whether the tumor cell lines contain SCF messenger RNA (mRNA). In addition, we tested tumor cell line supernatants for the presence of secreted SCF protein by enzyme immunoassay, and analyzed the tumor cell lines for membrane-bound SCF by indirect immunofluorescence. Our results show that the Du4475, H69, and H128 cell lines, as well as a melanoma cell line (HTT144), have multiple copies of SCF mRNA. Soluble SCF protein was detected in the cell supernatants in the Du4475 and H69 cell lines and SCF was found on the surface of all four cell lines. These data show that some human solid tumor cell lines display high-affinity c-kit receptors and produce SCF, which can be detected on the cell surface. These results suggest the possibility that autocrine production of SCF by c-kit receptor-bearing tumor cells may enhance cell growth in tumor cell lines.


Blood ◽  
1992 ◽  
Vol 80 (2) ◽  
pp. 374-381 ◽  
Author(s):  
AM Turner ◽  
KM Zsebo ◽  
F Martin ◽  
FW Jacobsen ◽  
LG Bennett ◽  
...  

Human stem cell factor (SCF) acts in the presence of other growth factors to stimulate the growth of primitive hematopoietic progenitor cells. These effects are performed by activation of the SCF receptor, c- kit. Because of the potential use of SCF in patients undergoing chemotherapy and bone marrow transplantation, the effect of SCF on nonhematopoietic tumors requires investigation. To determine whether human tumor cell lines display c-kit receptors, we performed binding experiments with 125I-SCF on a breast carcinoma cell line (Du4475), a gastric carcinoma cell line (KATO III), a melanoma cell line (HTT144), as well as two small cell lung carcinoma cell lines (H69 and H128). The biologic effect of SCF on tumor cell lines was assessed by its ability to stimulate tritiated thymidine uptake and to enhance colony growth in methylcellulose. The breast carcinoma cell line, Du4475, as well as two small cell lung carcinoma cell lines, H69 and H128, exhibit high- affinity c-kit receptors with approximate binding affinities of 40, 100, and 90 pmol/L, respectively. The number of high-affinity receptors per cell ranged from 700 to 9,500. The gastric carcinoma cell line, as well as the melanoma cell line, showed trace binding of 125I-SCF. In the presence of SCF alone, or in combination with granulocyte- macrophage colony-stimulating factor or interleukin-3, there was less than a 17% increase in the colony growth of Du4475, H69, or H128 cell lines. Postulating that the lack of growth response could be secondary to endogenous SCF production by the tumor cell lines, we used an RNAse protection assay to determine whether the tumor cell lines contain SCF messenger RNA (mRNA). In addition, we tested tumor cell line supernatants for the presence of secreted SCF protein by enzyme immunoassay, and analyzed the tumor cell lines for membrane-bound SCF by indirect immunofluorescence. Our results show that the Du4475, H69, and H128 cell lines, as well as a melanoma cell line (HTT144), have multiple copies of SCF mRNA. Soluble SCF protein was detected in the cell supernatants in the Du4475 and H69 cell lines and SCF was found on the surface of all four cell lines. These data show that some human solid tumor cell lines display high-affinity c-kit receptors and produce SCF, which can be detected on the cell surface. These results suggest the possibility that autocrine production of SCF by c-kit receptor-bearing tumor cells may enhance cell growth in tumor cell lines.


Heliyon ◽  
2020 ◽  
Vol 6 (3) ◽  
pp. e03640
Author(s):  
Abdullahi Bello Umar ◽  
Adamu Uzairu ◽  
Gideon Adamu Shallangwa ◽  
Sani Uba

2020 ◽  
Vol 3 (4) ◽  
pp. 1009-1022
Author(s):  
Abdullahi Bello Umar ◽  
Adamu Uzairu ◽  
Sani Uba ◽  
Gideon Adamu Shallangwa

2017 ◽  
Vol 10 (7) ◽  
Author(s):  
Ali Asghar Peyvandi ◽  
Shahrokh Khoshsirat ◽  
Akram Safaei ◽  
Mostafa Rezaei-Tavirani ◽  
Mona Azodi-Zamanian

2015 ◽  
Author(s):  
Parvathi Haridas ◽  
Jacqui A. McGovern ◽  
Ahishek S. Kashyap ◽  
D.L. Sean McElwain ◽  
Matthew Simpson

AbstractReliable identification of different melanoma cell lines is important for many aspects of melanoma research. Common markers used to identify melanoma cell lines include: S100; HMB-45; and Melan-A. We explore the expression of these three markers in four different melanoma cell lines: WM35; WM793; SK-MEL-28; and MM127. The expression of these markers is examined at both the mRNA and protein level. Our results show that the metastatic cell line, MM127, cannot be detected using any of the commonly used melanoma-associated markers. This implies that it would be very difficult to identify this particular cell line in a heterogeneous sample, and as a result this cell line should be used with care.


Author(s):  
G. V. Venkatakarthikeswari ◽  
R. Gayatri Devi ◽  
J. Selavaraj ◽  
A. Jothi Priya

Aegle marmelos is also known as bael which is commonly found in south East Asia and Indian-sub continent. The origin of bael is India. Bael is also known as the golden apple, Bengal-quince in India. In the ancient medical system, Aegle marmelos play an important role and its extract is also useful in inflammation, diabetes, cancer and asthma. The leaves are used for anti-inflammatory, nervous disorder, control blood sugar and fruit is used to treat antiviral, anti-diabetics, and brain and heart tonic. In addition, studies have proved that bael is used for the treatment and prevention of cancer. The main aim of this study is to assess the anti-cancer potential of Aegle marmelos fruit extract pro and anti apoptotic molecules in human melanoma cell line-A375. In the present study, Human Melanoma A375 cells will be produced, grown and will be passed in different culture flasks, then RNA isolation was done and by reverse transcriptase process, RNA gets converted into cDNA. This cDNA will be used for the amplification of growth factor beta using gene specific primers by commercially available real time PCR kit.  The anticancer potential effect was found in 400µg/ml, as the concentration increases, the cell viability is decreased. The current study explains the potential application of bael in pharmacological and medicinal uses in near future.


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