scholarly journals Spontaneously-forming spheroids as an in vitro cancer cell model for anticancer drug screening

Oncotarget ◽  
2015 ◽  
Vol 6 (25) ◽  
pp. 21255-21267 ◽  
Author(s):  
Maria A. Theodoraki ◽  
Celso O. Rezende ◽  
Oraphin Chantarasriwong ◽  
Adriana D. Corben ◽  
Emmanuel A. Theodorakis ◽  
...  
Author(s):  
Kristina V. Kitaeva ◽  
Catrin S. Rutland ◽  
Albert A. Rizvanov ◽  
Valeriya V. Solovyeva

2008 ◽  
Vol 21 (4) ◽  
pp. 1289-1296 ◽  
Author(s):  
Xulang Zhang ◽  
Wei Wang ◽  
Weiting Yu ◽  
Yubing Xie ◽  
Xiaohui Zhang ◽  
...  

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Maya E. W. Moningka

Abstract: Recent anticancer drug development aims to molecular aspect with more specific target without harming healthy cells. Natural resources have been providing promising new anticancer drugs. Terpineol, an essential oil, is one of the anti-breast cancer candidates. Terpineol can be made from turpentine, which is non-wood product of pine tree latex. Alpha-terpineol isolated from terpineol has an anticancer potency and has been proven to inhibit the growth and induce cancer cell death in vitro by inhibiting NF-κB. P53 is a tumor suppressor gene which triggers apoptosis when irreparable DNA damage occurs. Activity of p53 can be altered and/or inhibited by mutation and inactivation of other oncogenes. The main mechanism underlying apoptosis is caspase (cysteine aspartic acid protease) activity. One of the caspases responsible for apoptosis is caspase 3. This caspase 3 can be activated by either intrinsic (mitochondrial signaling) or extrinsic (death ligand) mechanism; the latter involves caspase 8 and 9. Activated caspase 3 will execute the apoptosis inside the cells. Cytotoxic activity of α-terpineol and its involvement in apoptosis, p53 expression, and caspase 3 activities in cancer cell cultures are still being investigated to determine their anticancer activities and the possibility of anticancer drug development.Keywords: cancer therapy, terpineol, p53, caspase-3 Abstrak: Pengembangan obat antikanker saat ini lebih ditujukan pada aspek molekuler dengan adanya target terapi yang lebih spesifik sehingga lebih aman untuk sel-sel tubuh yang normal. Dewasa ini, eksplorasi terhadap bahan alam untuk kandidat obat antikanker semakin dilirik. Minyak esensial terpineol merupakan salah satu bahan pada komposisi obat antikanker payudara. Terpineol dapat dibuat dari terpentin yang merupakan hasil hutan non kayu dari pohon pinus, dengan cara mengambil getahnya. Dari terpineol diisolasi senyawa α-terpineol yang berpotensi sebagai antikanker serta telah terbukti dapat menghambat pertumbuhan dan menginduksi kematian sel tumor melalui mekanisme yang melibatkan inhibisi aktivitas NFкB. Gen p53 merupakan gen tumor supresor yang memicu terjadinya suatu kematian sel atau apoptosis bila terdapat kerusakan DNA dalam upayanya untuk mengatur proliferasi sel. Selain karena adanya mutasi gen p53, inaktivasi dapat terjadi oleh overekspresi onkogen yang nantinya berikatan dengan p53 dan menghambat kerja gen tersebut. Mekanisme utama yang juga mendasari terjadinya apoptosis ialah aktivitas cysteine aspartic acid protease (caspase). Salah satu caspase yang berperan dalam menginduksi apoptosis ialah caspase 3. Caspase ini dapat diaktifkan melalui mekanisme intrinsik (jalur mitokondrial) maupun ekstrinsik (death ligand), dengan bantuan caspase 8 dan caspase 9. Bila caspase 3 teraktifkan maka sebagai caspase eksekutor, akan melakukan tugasnya untuk mengapoptosis sel. Kajian aktivitas sitotoksik senyawa α-terpineol terhadap suatu cell line, pengaruh senyawa tersebut terhadap proses apoptosis, ekspresi p53, dan aktivitas caspase 3 pada berbagai macam kanker masih terus diteliti dalam perkembangannya sebagai obat anti kanker.Kata kunci: terapi kanker, terpineol, p53, caspase-3


Pharmaceutics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 587 ◽  
Author(s):  
Ina Puscas ◽  
Florian Bernard-Patrzynski ◽  
Martin Jutras ◽  
Marc-André Lécuyer ◽  
Lyne Bourbonnière ◽  
...  

Since most preclinical drug permeability assays across the blood-brain barrier (BBB) are still evaluated in rodents, we compared an in vitro mouse primary endothelial cell model to the mouse b.End3 and the acellular parallel artificial membrane permeability assay (PAMPA) models for drug screening purposes. The mRNA expression of key feature membrane proteins of primary and bEnd.3 mouse brain endothelial cells were compared. Transwell® monolayer models were further characterized in terms of tightness and integrity. The in vitro in vivo correlation (IVIVC) was obtained by the correlation of the in vitro permeability data with log BB values obtained in mice for seven drugs. The mouse primary model showed higher monolayer integrity and levels of mRNA expression of BBB tight junction (TJ) proteins and membrane transporters (MBRT), especially for the efflux transporter Pgp. The IVIVC and drug ranking underlined the superiority of the primary model (r2 = 0.765) when compared to the PAMPA-BBB (r2 = 0.391) and bEnd.3 cell line (r2 = 0.019) models. The primary monolayer mouse model came out as a simple and reliable candidate for the prediction of drug permeability across the BBB. This model encompasses a rapid set-up, a fair reproduction of BBB tissue characteristics, and an accurate drug screening.


BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Christian Linke ◽  
Markus Wösle ◽  
Anja Harder

Abstract Background Anticancer compound 3-bromopyruvate (3-BrPA) suppresses cancer cell growth via targeting glycolytic and mitochondrial metabolism. The malignant peripheral nerve sheath tumor (MPNST), a very aggressive, therapy resistant, and Neurofibromatosis type 1 associated neoplasia, shows a high metabolic activity and affected patients may therefore benefit from 3-BrPA treatment. To elucidate the specific mode of action, we used a controlled cell model overexpressing proteasome activator (PA) 28, subsequently leading to p53 inactivation and oncogenic transformation and therefore reproducing an important pathway in MPNST and overall tumor pathogenesis. Methods Viability of MPNST cell lines S462, NSF1, and T265 in response to increasing doses (0–120 μM) of 3-BrPA was analyzed by CellTiter-Blue® assay. Additionally, we investigated viability, reactive oxygen species (ROS) production (dihydroethidium assay), nicotinamide adenine dinucleotide dehydrogenase activity (NADH-TR assay) and lactate production (lactate assay) in mouse B8 fibroblasts overexpressing PA28 in response to 3-BrPA application. For all experiments normal and nutrient deficient conditions were tested. MPNST cell lines were furthermore characterized immunohistochemically for Ki67, p53, bcl2, bcl6, cyclin D1, and p21. Results MPNST significantly responded dose dependent to 3-BrPA application, whereby S462 cells were most responsive. Human control cells showed a reduced sensitivity. In PA28 overexpressing cancer cell model 3-BrPA application harmed mitochondrial NADH dehydrogenase activity mildly and significantly failed to inhibit lactate production. PA28 overexpression was associated with a functional glycolysis as well as a partial resistance to stress provoked by nutrient deprivation. 3-BrPA treatment was not associated with an increase of ROS. Starvation sensitized MPNST to treatment. Conclusions Aggressive MPNST cells are sensitive to 3-BrPA therapy in-vitro with and without starvation. In a PA28 overexpression cancer cell model leading to p53 inactivation, thereby reflecting a key molecular feature in human NF1 associated MPNST, known functions of 3-BrPA to block mitochondrial activity and glycolysis were reproduced, however oncogenic cells displayed a partial resistance. To conclude, 3-BrPA was sufficient to reduce NF1 associated MPNST viability potentially due inhibition of glycolysis which should lead to the initiation of further studies and promises a potential benefit for NF1 patients.


Author(s):  
J. Chakraborty ◽  
A. Von Stein ◽  
S. K. Saha

In spite of continuous efforts by numerous investigators, no ideal animal or in vitro cell model has so far been established for the human prostatic cancer cells. A human prostatic cancer cell line, DU 145, established by Stone et al. (1), provides a useful model for the basic understanding of malignant growth of this cell type. DU 145 has been characterized as an epithelial cell line, which retains most of its original growth characteristics (1,2). We are using this cell line as in vitro model system for biochemical, immunological and morphometric analyses, to understand the subcellular and molecular changes in these cells leading to their malignant transformation. The present paper is our first report describing a detailed characterization of DU 145 cell line.


Author(s):  
Yi Gao ◽  
Yue Zhu ◽  
Xiaopeng Xu ◽  
Fangjun Wang ◽  
Weidong Shen ◽  
...  

ObjectiveThe emergence of multi-drug resistance (MDR) in esophageal carcinoma has severely affected the effect of chemotherapy and shortened the survival of patients. To this end, we intend to develop a biomimetic nano-targeting drug modified by cancer cell membrane, and investigate its therapeutic effect.MethodsThe degradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) co-loaded with doxorubicin (DOX) and curcumin (Cur) were prepared by solvent evaporation method. TE10 cell membrane and Distearoyl phosphatidylethanolamine-polyethylene glycol (DSPE-PEG) were then coated on the PLGA NPs by membrane extrusion to prepare the PEG-TE10@PLGA@DOX-Cur NPs (PMPNs). Size and zeta potential of the PMPNs were analyzed by lazer particle analyzer, and the morphology of PMPNs was observed by transmission electron microscope. The TE10 cell membrane protein on PMPNs was analyzed by gel electrophoresis. The DOX-resistant esophageal cancer cell model TE10/DOX was established through high-dose induction. The In vitro homologous targeting ability of PMPNs was evaluated by cell uptake assay, and the in vitro anti-tumor effect of PMPNs was assessed through CCK-8, clone formation and flow cytometry. A Balb/c mouse model of TE10/DOX xenograft was constructed to evaluate the anti-tumor effect in vivo and the bio-safety of PMPNs.ResultsThe prepared cell membrane coated PMPNs had a regular spherical structure with an average diameter of 177 nm. PMPNs could directly target TE10 and TE10/DOX cells or TE10/DOX xenografted tumor and effectively inhibit the growth of DOX-resistant esophageal carcinoma. Besides, the PMPNs was confirmed to have high biosafety.ConclusionIn this study, a targeted biomimetic nano-drug delivery system PMPNs was successfully prepared, which overcome the MDR of esophageal carcinoma by co-delivering DOX and sensitizer curcumin.


Author(s):  
Vitor M. Almeida ◽  
Maximino Alencar Bezerra Jr. ◽  
Jéssica C. Nascimento ◽  
Lidia Maria F. Amorim

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