scholarly journals Monocyte Infiltration and Differentiation in 3D Multicellular Spheroid Cancer Models

Pathogens ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 969
Author(s):  
Natasha Helleberg Madsen ◽  
Boye Schnack Nielsen ◽  
Son Ly Nhat ◽  
Søren Skov ◽  
Monika Gad ◽  
...  

Tumor-associated macrophages often correlate with tumor progression, and therapies targeting immune cells in tumors have emerged as promising treatments. To select effective therapies, we established an in vitro 3D multicellular spheroid model including cancer cells, fibroblasts, and monocytes. We analyzed monocyte infiltration and differentiation in spheroids generated from fibroblasts and either of the cancer cell lines MCF-7, HT-29, PANC-1, or MIA PaCa-2. Monocytes rapidly infiltrated spheroids and differentiated into mature macrophages with diverse phenotypes in a cancer cell line-dependent manner. MIA PaCa-2 spheroids polarized infiltrating monocytes to M2-like macrophages with high CD206 and CD14 expression, whereas monocytes polarized by MCF-7 spheroids displayed an M1-like phenotype. Monocytes in HT-29 and PANC-1 primarily obtained an M2-like phenotype but also showed upregulation of M1 markers. Analysis of the secretion of 43 soluble factors demonstrated that the cytokine profile between spheroid cultures differed considerably depending on the cancer cell line. Secretion of most of the cytokines increased upon the addition of monocytes resulting in a more inflammatory and pro-tumorigenic environment. These multicellular spheroids can be used to recapitulate the tumor microenvironment and the phenotype of tumor-associated macrophages in vitro and provide more realistic 3D cancer models allowing the in vitro screening of immunotherapeutic compounds.

2021 ◽  
Vol 26 (6) ◽  
pp. 3120-3128
Author(s):  
M. AYDIN AKBUDAK ◽  
TEVHIDE SUT ◽  
NURANIYE ERUYGUR ◽  
ERSIN AKINCI

The Epilobium species, rich in various active phytochemicals, have been widely used in folk medicine to treat several diseases including benign prostatic hyperplasia. Despite being demonstrated on some type of cancer cells such as prostate cancer, their potential anti-cancerous role on colorectal adenocarcinoma cells has not been studied yet. According to the World Health Organization (WHO), colon cancer is the third most common form of cancer, resulting over 800 000 deaths every year worldwide. The present study demonstrates the anti-cancerous activity of aqueous and ethanolic Epilobium parviflorum extracts in colon cancer cell line HT-29 cells in vitro. The both type of extracts reduced the cell viability of HT-29 cells in a dose dependent manner. Gene expression analysis of HT-29 cells demonstrated an increase at apoptotic genes, caspase 3 and caspase 8. Nuclear fragmentation of apoptotic cells was also demonstrated through TUNEL assay as well as immunostaining experiments. On the other hand, same lethal concentrations of E. parviflorum extracts were not profound on non-cancerous human fibroblast cell line BJ cells. Our results indicate that E. parviflorum may also be used as a therapeutic agent against colon cancers.


2020 ◽  
Author(s):  
M. AYDIN AKBUDAK ◽  
Tevhide SUT ◽  
Nuraniye ERUYGUR ◽  
Ersin AKINCI

The Epilobium species are rich in various active phytochemicals and have seen wide use in folk medicine to treat several diseases, including benign prostatic hyperplasia. Although their benefits have been demonstrated on certain types of cancer cells, such as prostate cancer cells, their potential antiproliferative effects on colorectal adenocarcinoma cells have yet to be studied. The present study exhibited the antiproliferative activity of aqueous and ethanolic Epilobium parviflorum extracts in a colon cancer cell line, HT-29 cells in vitro. Both types of extracts reduced the cell viability of HT-29 cells in a dose-dependent manner. A gene expression analysis of the HT-29 cells demonstrated an increase in apoptotic genes, Caspase-3 and Caspase-8. Nuclear fragmentation of the apoptotic cells was also demonstrated through TUNEL assay and immunostaining experiments. On the other hand, the same lethal concentrations of the E. parviflorum extracts did not significantly affect a non-cancerous human fibroblast cell line, BJ cells. Our results confirmed that aqueous and ethanolic Epilobium parviflorum extracts can eliminate proliferation of human colorectal carcinoma cells in vitro. E. parviflorum may have the potential to become a therapeutic agent against colon cancers.


2018 ◽  
Vol 18 (17) ◽  
pp. 1483-1493
Author(s):  
Ricardo Imbroisi Filho ◽  
Daniel T.G. Gonzaga ◽  
Thainá M. Demaria ◽  
João G.B. Leandro ◽  
Dora C.S. Costa ◽  
...  

Background: Cancer is a major cause of death worldwide, despite many different drugs available to treat the disease. This high mortality rate is largely due to the complexity of the disease, which results from several genetic and epigenetic changes. Therefore, researchers are constantly searching for novel drugs that can target different and multiple aspects of cancer. Experimental: After a screening, we selected one novel molecule, out of ninety-four triazole derivatives, that strongly affects the viability and proliferation of the human breast cancer cell line MCF-7, with minimal effects on non-cancer cells. The drug, named DAN94, induced a dose-dependent decrease in MCF-7 cells viability, with an IC50 of 3.2 ± 0.2 µM. Additionally, DAN94 interfered with mitochondria metabolism promoting reactive oxygen species production, triggering apoptosis and arresting the cancer cells on G1/G0 phase of cell cycle, inhibiting cell proliferation. These effects are not observed when the drug was tested in the non-cancer cell line MCF10A. Using a mouse model with xenograft tumor implants, the drug preventing tumor growth presented no toxicity for the animal and without altering biochemical markers of hepatic function. Results and Conclusion: The novel drug DAN94 is selective for cancer cells, targeting the mitochondrial metabolism, which culminates in the cancer cell death. In the end, DAN94 has been shown to be a promising drug for controlling breast cancer with minimal undesirable effects.


2020 ◽  
Vol 17 (2) ◽  
pp. 151-159
Author(s):  
Tran Nguyen Minh An ◽  
Pham Thai Phuong ◽  
Nguyen Minh Quang ◽  
Nguyen Van Son ◽  
Nguyen Van Cuong ◽  
...  

: A series of novel 1,3-thiazole derivatives (5a-i) with a modified phenothiazine moiety were synthesized and tested against cancer cell line MCF-7 for their cytotoxicity. Most of them (5a-i) were less cytotoxic or had no activity against MCF-7 cancer cell line. Material and Methods: The IC50 value of compound (4) was 33.84 μM. The compounds (5a-i) were also evaluated for antimicrobial activities, but no significant activity was observed. The antioxidant activity was conducted for target compounds (5a-i). The IC50 value of compound (5b) was 0.151mM. Results: The total amount of energy, ACE (atomic contact energy), energy of receptor (PDB: 5G5J), and ligand interaction of structure (4) were found to be 22.448 Kcal.mol-1 , -247.68, and -91.91 Kcal.mol-1, respectively. The structure (4) is well binded with the receptor because the values of binding energy, steric energy, and the number of hydrogen bondings are -91.91, 22.448 kcal.mol-1, and 2, respectively. It shows that structure (4) has good cytotoxicity with MCF-7 in vitro. Conclusion: The increasing of docking ability of structures (5a-i) with the receptor is presented in increasing order as (5f)>(5e)>(5g)>(5a)>(5b)>(5d)>(5c)>(5i)>(5h). The structure bearing substitution as thiosemicarbazone (4), nitrogen heterocyclic (5f), halogen (5e), and azide (5g) showed good cytotoxicity activity in vitro.


2018 ◽  
Vol 18 (4) ◽  
pp. 573-582 ◽  
Author(s):  
Khaled R.A. Abdellatif ◽  
Mostafa M. Elbadawi ◽  
Mohammed T. Elsaady ◽  
Amer A. Abd El-Hafeez ◽  
Takashi Fujimura ◽  
...  

Background: Some 2-thioxoimidazolidinones have been reported as anti-prostate and anti-breast cancer agents through their inhibitory activity on topoisomerase I that is considered as a potential chemotherapeutic target. Objective: A new series of 3,5-disubstituted-2-thioxoimidazolidinone derivatives 10a-f and their S-methyl analogs 11a-f were designed, synthesized and evaluated for cytotoxicity against human prostate cancer cell line (PC-3), human breast cancer cell line (MCF-7) and non-cancerous human lung fibroblast cell line (WI-38). </P><P> Results and Method: While compounds 10a-f showed a broad range of activities against PC-3 and MCF-7 cell lines (IC50 = 34.0 – 186.9 and 24.6 – 147.5 µM respectively), the S-methyl analogs 11a-f showed (IC50 = 22.7 – 198.5 and 16.9 – 188.2 µM respectively) in comparison with 5-fluorouracil (IC50 = 60.7 and 40.7 µM respectively). 11c (IC50 = 22.7 and 29.2 µM) and 11f (IC50 = 28.7 and 16.9 µM) were the most potent among all compounds against both PC-3 and MCF-7 respectively with no cytotoxicity against WI-38. Conclusion: The newly synthesized compounds showed good activity against PC-3 and MCF-7 cell lines in comparison with 5-fluorouracil. Compounds 11c and 11f bound with human topoisomerase I similar to its known inhibitors and significantly inhibited its DNA relaxation activity in a dose dependent manner which may rationalize their molecular mechanism as cytotoxic agents.


2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Vincenza Barresi ◽  
Carmela Bonaccorso ◽  
Domenico A. Cristaldi ◽  
Maria N. Modica ◽  
Nicolò Musso ◽  
...  

Recent drug discovery efforts are highly focused towards identification, design, and synthesis of small molecules as anticancer agents. With this aim, we recently designed and synthesized novel compounds with high efficacy and specificity for the treatment of breast tumors. Based on the obtained results, we constructed a Volsurf+ (VS+) model using a dataset of 59 compounds able to predict the in vitro antitumor activity against MCF-7 cancer cell line for new derivatives. In the present paper, in order to further verify the robustness of this model, we report the results of the projection of more than 150 known molecules and 9 newly synthesized compounds. We predict their activity versus MCF-7 cell line and experimentally verify the in silico results for some promising chosen molecules in two human breast cell lines, MCF-7 and MDA-MB-231.


2018 ◽  
Vol 7 (3) ◽  
pp. 424
Author(s):  
Yuastika Puspita Sari ◽  
Hirowati Ali ◽  
Aswiyanti Asri

Kanker payudara yang paling banyak ditemukan adalah subtipe luminal A dengan karakteristik Estrogen Reseptor+. Subjek penelitian akan diwakili oleh cell line MCF-7 dan Umbilical Cord Blood Mesenchymal Stem Cell (UCBMSC). Over expression Myc pada kanker payudara mengakibatkan sel kanker menjadi lebih invasif dan terjadi resistensi terhadap terapi hormonal. Tujuan penelitian ini adalah mengidentifikasi ekspresi gen Myc pada cell line MCF-7 sebelum dan sesudah pemberian sel punca. Penelitian ini menggunakan desain experimental secara in vitro. Sampel menggunakan MCF-7 dan sel punca yang dibagi menjadi 4 kelompok, yaitu K1 (kelompok kontrol MCF-7), K2 (kelompok kontrol sel punca), P1 (perlakuan subkultur MCF-7 dengan sel punca inkubasi 24 jam), dan P2 (inkubasi 48 jam). Kemudian, dilakukan isolasi RNA, sintesis cDNA, dan ekspresi Myc diperiksa menggunakan PCR dan elektroforesis. Analisa data yang digunakan adalan One Way ANOVA dan post-hoc LSD. Hasil analisis bivariat didapatkan p<0,05. Dari uji post-hoc LSD tidak ditemukan perbedaan yang bermakna antara K1 dengan P1, K1 dengan P2, dan K2 dengan P2. Namun, tetap ditemukan perbedaan yang bermakna antara K2 dengan P1 dan P1 dengan P2. Simpulan penelitian ini adalah tidak terdapat perbedaan bermakna ekspresi gen Myc pada subkultur antara MCF-7 breast cancer cell line dengan pemberian sel punca mesenkimal.


INDIAN DRUGS ◽  
2020 ◽  
Vol 57 (06) ◽  
pp. 49-59
Author(s):  
Priyambada Kshiroda Nandini Sarangi ◽  
Jyotirmaya Sahoo ◽  
Chita Ranjan Sahoo ◽  
Sudhir Kumar Paidesetty ◽  
Guru Prasad Mohanta

A series of eight quinoline-thiazole hybrid-bearing diazenylsulfonamides, 4a-4h, were synthesized and characterized by UV-Vis, FT/IR, 1H NMR and lC-MS. These compounds were formed when two prepared intermediate precursors of Schiff-base compounds, (E)-N-((2-chloroquinolin-3-yl)methylene)-4phenylthiazol-2-amine (3a) and (E)-N-((2-chloroquinolin-3-yl)methylene)-4-chlorophenylthiazol-2-amine (3b) were converted to the corresponding diazenyl compounds 4a-4h by treating and coupling with the individual diazonium salts of sulfa-drugs. The results of in vitro cytotoxic activity of the synthesized compounds in two cancer cell lines MCF 7 (human breast cancer cell line) and K562 (myelogenousleukemia cell line) have shown the IC50 values as given: 4b against MCF 7 19.52 and against K562 20.55µM; 4d against MCF 7 15.96 and against K562 13.05µM. Moreover, the compound 4-(((Z)-(2-chloroquinolin-3yl)(4-phenylthiazol-2-ylimino)methyl)diazenyl)benzenesulfonic acid (4d) induced maximum percentage of apoptosis. Furthermore, the in vitro antioxidant activity study revealed that among all the synthesized compounds, compound 4d has an excellent radical scavenging effect. Molecular docking was additionally performed to investigate the binding affinity of H-bonding interaction of synthesized compounds with a targeted enzyme and to compare it with the anticancer drugs, dasatinib, bosutinib and dacarbazine.


2020 ◽  
Vol 11 (SPL4) ◽  
pp. 805-808
Author(s):  
Ravikumar Raju ◽  
Teja ◽  
Sravanathi P ◽  
Muthu Babu K

Breast cancer is the subsequent foremost reason of cancer death in a woman and ranks as the primary foremost reason of death in India. In its conduct, several measures and recommendation are considered. Homoeopathic medicines are one of the part of a corresponding, and another medicine is utilized for the treatment of cancer. The main purpose of the investigation is to evaluate the anticancer action of homoeopathic arrangements of Asterias rubens  on the basis of the similia principle. We directed an in vitro study using MTT assay to control the result of ultra diluted homoeopathic preparation in contradiction of two human breast glandular cancer cell lines(MCF-7 and MDA-MD- 231), frequently used for the breast cancer treatment, by testing the feasibility of breast cancer (MCF-7 and MDA-MD-231) cell line, with various attenuations of Asterias rubens  at 24 hrs. Multiple comparisons between tested reagents at different concentrations confirmed the significance of the said results. At a dilution of 1:25 6CH and 30CH potency shown superior activity on MCF-7 and no such significant changes on MDA-MD-231 at any dilutions As it fails to offer estrogen receptor(ER) Also progesterone receptor (PR) expression, and also HER2 (human epidermal development variable receptor2) so continuously a triple-negative breast cancer it will be a hostility manifestation for breast cancer with restricted medicine choices. However, further potency needs to be tested. These preliminary significant results warrant further in vitro and in vivo studies to estimate the possible of Asterias rubens  a medicine to treat breast cancer.


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