Epoxylathyrol Derivatives: Modulation of ABCB1-Mediated Multidrug Resistance in Human Colon Adenocarcinoma and Mouse T-Lymphoma Cells

2015 ◽  
Vol 78 (9) ◽  
pp. 2215-2228 ◽  
Author(s):  
Ana M. Matos ◽  
Mariana Reis ◽  
Noélia Duarte ◽  
Gabriella Spengler ◽  
Joseph Molnár ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Colon Adenocarcinoma ◽  
Human Colon ◽  
Lymphoma Cells ◽  
T Lymphoma Cells ◽  
T Lymphoma ◽  
Human Colon Adenocarcinoma

Stable differentiation of a human colon adenocarcinoma cell line by sodium butyrate is associated with multidrug resistance

1994 ◽  
Vol 160 (2) ◽  
pp. 213-226 ◽  
Author(s):  
Samuel B. Ho ◽  
Pei-Sha Yan ◽  
Rajvir Dahiya ◽  
Brent A. Neuschwander-Tetri ◽  
Carol Basbaum ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Cell Line ◽  
Sodium Butyrate ◽  
Colon Adenocarcinoma ◽  
Human Colon ◽  
Adenocarcinoma Cell Line ◽  
Adenocarcinoma Cell ◽  
Human Colon Adenocarcinoma

scholarly journals Pyruvate Treatment Restores the Effectiveness of Chemotherapeutic Agents in Human Colon Adenocarcinoma and Pleural Mesothelioma Cells

2018 ◽  
Vol 19 (11) ◽  
pp. 3550 ◽  
Author(s):  
Eleonora Mungo ◽  
Loredana Bergandi ◽  
Iris Salaroglio ◽  
Sophie Doublier
Keyword(s):  
Multidrug Resistance ◽  
Cancer Cells ◽  
Colon Adenocarcinoma ◽  
Glucose Consumption ◽  
Mitochondrial Respiratory Chain ◽  
Human Colon ◽  
Chemotherapeutic Agents ◽  
Cross Resistance ◽  
Ht29 Cells ◽  
Human Colon Adenocarcinoma

Emerging evidence supports the idea that a dysfunction in cell metabolism could sustain a resistant phenotype in cancer cells. As the success of chemotherapeutic agents is often questioned by the occurrence of multidrug resistance (MDR), a multiple cross-resistance towards different anti-cancer drugs represent a major obstacle to cancer treatment. The present study has clarified the involvement of the carbon metabolites in a more aggressive tumor colon adenocarcinoma phenotype and in a chemoresistant mesothelioma, and the role of pyruvate treatment in the reversion of the potentially related resistance. For the first time, we have shown that human colon adenocarcinoma cells (HT29) and its chemoresistant counterpart (HT29-dx) displayed different carbon metabolism: HT29-dx cells had a higher glucose consumption compared to HT29 cells, whereas human malignant mesothelioma (HMM) cells showed a lower glucose consumption compared to HT29 cells, accompanied by a lower pyruvate production and, consequently, a higher production of lactate. When treated with pyruvate, both HT29-dx and HMM cells exhibited a re-established accumulation of doxorubicin and a lower survival ability, a decreased activity of multidrug resistance protein 1 (MRP1) and a restored mitochondrial respiratory chain function, improving the effectiveness of the chemotherapeutic agents in these resistant cancer cells.

An insight into the structure of 5-spiro aromatic derivatives of imidazolidine-2,4-dione, a new group of very potent inhibitors of tumor multidrug resistance in T-lymphoma cells

2021 ◽  
Vol 109 ◽  
pp. 104735
Author(s):  
Ewa Żesławska ◽  
Katarzyna Kucwaj-Brysz ◽  
Annamária Kincses ◽  
Gabriella Spengler ◽  
Ewa Szymańska ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Lymphoma Cells ◽  
T Lymphoma Cells ◽  
T Lymphoma ◽  
Derivatives Of ◽  
Insight Into

In Vitro and in Vivo Comparison of Binding of 99m-Tc-Iabeled Anti-CEA MAb F33-104 with 99m-Tc-labeled Anti-CEA MAb BW431/26

1999 ◽  
Vol 38 (04) ◽  
pp. 115-119
Author(s):  
N. Oriuchi ◽  
S. Sugiyama ◽  
M. Kuroki ◽  
Y. Matsuoka ◽  
S. Tanada ◽  
...  
Keyword(s):  
Nude Mice ◽  
Binding Capacity ◽  
Colon Adenocarcinoma ◽  
Human Colon ◽  
Cell Binding ◽  
Vitro Binding ◽  
Labeling Method ◽  
Human Colon Adenocarcinoma

Summary Aim: The purpose of this study was to assess the potential for radioimmunodetection (RAID) of murine anti-carcinoembryonic antigen (CEA) monoclonal antibody (MAb) F33-104 labeled with technetium-99m (99m-Tc) by a reduction-mediated labeling method. Methods: The binding capacity of 99m-Tc-labeled anti-CEA MAb F33-104 with CEA by means of in vitro procedures such as immunoradiometric assay and cell binding assay and the biodistribution of 99m-Tc-labeled anti-CEA MAb F33-104 in normal nude mice and nude mice bearing human colon adenocarcinoma LS180 tumor were investigated and compared with 99m-Tc-labeled anti-CEA MAb BW431/26. Results: The in vitro binding rate of 99m-Tc-labeled anti-CEA MAb F33-104 with CEA in solution and attached to the cell membrane was significantly higher than 99m-Tclabeled anti-CEA MAb BW431/261 (31.4 ± 0.95% vs. 11.9 ± 0.55% at 100 ng/mL of soluble CEA, 83.5 ± 2.84% vs. 54.0 ± 2.54% at 107 of LS 180 cells). In vivo, accumulation of 99m-Tc-labeled anti-CEA MAb F33-104 was higher at 18 h postinjection than 99m-Tc-labeled anti-CEA MAb BW431/26 (20.1 ± 3.50% ID/g vs. 14.4 ± 3.30% ID/g). 99m-Tcactivity in the kidneys of nude mice bearing tumor was higher at 18 h postinjection than at 3 h (12.8 ± 2.10% ID/g vs. 8.01 ± 2.40% ID/g of 99m-Tc-labeled anti-CEA MAb F33-104, 10.7 ± 1.70% ID/g vs. 8.10 ± 1.75% ID/g of 99m-Tc-labeled anti-CEA MAb BW431/26). Conclusion: 99m-Tc-labeled anti-CEA MAb F33-104 is a potential novel agent for RAID of recurrent colorectal cancer.

Design, Synthesis, In Vitro Anti-cancer Activity, ADMET Profile and Molecular Docking of Novel Triazolo[3,4-a]phthalazine Derivatives Targeting VEGFR-2 Enzyme

2018 ◽  
Vol 18 (8) ◽  
pp. 1184-1196 ◽  
Author(s):  
Abdel-Ghany A. El-Helby ◽  
Helmy Sakr ◽  
Rezk R.A. Ayyad ◽  
Khaled El-Adl ◽  
Mamdouh M. Ali ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Docking ◽  
Cell Lines ◽  
Colon Adenocarcinoma ◽  
Human Colon ◽  
Kinase Assay ◽  
Anticancer Activities ◽  
In Silico Admet ◽  
Human Colon Adenocarcinoma ◽  
Mcf 7

Background: Extensive studies were reported in the synthesis of several phthalazine derivatives as promising anticancer agents as potent VEGFR-2 inhibitors. Vatalanib (PTK787) was the first anilinophthalazine published derivative as a potent inhibitor of VEGFR. The discovery of vatalanib as a clinical candidate led to the design and synthesis of different anilinophthalazine derivatives as potent inhibitors for VEGFR-2. The objective of present research work is the synthesis of new agents with the same essential pharmacophoric features of the reported and clinically used VEGFR-2 inhibitors (e.g vatalanib and sorafenib). The main core of our molecular design rationale comprised bioisosteric modification strategies of VEGFR-2 inhibitors at four different positions. </P><P> Material and Methods: A correlation between structure and biological activity of our designed phthalazines was established using molecular docking and VEGFR-2 kinase assay. Results and Discussion: In view of their expected anticancer activity, novel triazolo[3,4-a]phthalazine derivatives 5-6a-o and 3-substituted-bis([1,2,4]triazolo)[3,4-a:4',3'-c]phthalazines 9a-b were designed, synthesized and evaluated for their anti-proliferative activity against two human tumor cell lines HCT-116 human colon adenocarcinoma and MCF-7 breast cancer. It was found that, compound 6o the most potent derivative against both HCT116 and MCF-7 cancer cell lines. Compounds 6o, 6m, 6d and 9b showed the highest anticancer activities against HCT116 human colon adenocarcinoma with IC50 of 7±0.06, 13±0.11, 15±0.14 and 23±0.22 µM respectively while compounds 6o, 6d, 6a and 6n showed the highest anticancer activities against MCF-7 breast cancer with IC50 of 16.98±0.15, 18.2±0.17, 57.54±0.53 and 66.45±0.67 µM respectively. Sorafenib as a highly potent VEGFR-2 inhibitor was used as a reference drug with IC50 of 5.47±0.3 and 7.26±0.3 µM respectively. Nine compounds were further evaluated for their VEGFR-2 inhibitory activity. Compounds 6o, 6m, 6d and 9b emerged as the most active counterparts against VEGFR-2 with IC50 values of 0.1±0.01, 0.15±0.02, 0.28±0.03 and 0.38±0.04 µM, respectively comparable to that of sorafenib (IC50 = 0.1±0.02) µM. Furthermore, molecular docking studies were carried out for all synthesized compounds to investigate their binding pattern and predict their binding affinities towards VEGFR-2 active site. In silico ADMET studies were calculated for the tested compounds. Most of our designed compounds exhibited good ADMET profile. Conclusion: The obtained results showed that, the most active compounds could be useful as a template for future design, optimization, adaptation and investigation to produce more potent and selective VEGFR-2 inhibitors with higher anticancer analogs.

Sign in / Sign up

Export Citation Format

Share Document