scholarly journals The Cytotoxic Effect of Metformin on RD Cell Line.

Background: Cancer is a pathogenesis that happens when modification in collections of normally occurring cells inside the human body occurs leading to non-controlled growth causing a lump called the tumor; this applies to all types of cancers except leukemia (cancer of the blood). Doxorubicin (DOX) is one of the highly effective anti-neoplastic drugs of the anthracycline's family used to treat many pediatric and adult cancers, e.g. solid tumors, lymphomas, leukemia and breast cancer. Doxorubicin is known to produce severe cytotoxicity. Metformin (Met) is a biguanide used for type 2 diabetes mellitus. Metformin have cytoprotective effect in addition to reducing basal and postprandial levels of glucose by decreasing the production of ROS, maintaining energy homeostasis and apoptosis regulation by its activation of adenosine monophosphate-activated protein kinase (AMPK). Met has also the ability to increase apoptotic factors and suppression of proliferation thus MET consider as cytotoxic and anti-proliferative drug. Objectives: This study was designed to investigate the cytotoxic and antiproliferative effect of Met comparing to DOX as a control in RD cell, also combination of both. Materials and Methods: Cell lines that used (Epithelial cells as a normal cell line and RD cell line was taken from human breast cancer) cultured in suitable media potentiated with different concentrations of heat-inactivated human serum. MTT assay (3-(4,5-Dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide) using for detection of cytotoxicity in Epithelial and RD cell lines for duration 72hrs. Results: The results showed that treatment with DOX, MET and combination DOX with MET there is significant (p≤ 0.5) cytotoxic, apoptotic and antiproliferative effect and there is potentiation effect between MET and DOX on tumor cells when treated by combination DOX with MET also Met showed a valuable cytotoxic effect through the detection of IC50. Conclusion: From the results, it can be concluded that Metformin have a good cytotoxic and antiproliferative effect on tumor cell lines.

Author(s):  
Muhammad Bahi ◽  
Claus Jacob ◽  
Khairan Khairan

The objective of this research was to investigate cytotoxicity effect of Haarlem oil (HO) on HL-60 cell line and Steinernema feltiae (S. feltiae). The test results using trypan blue method and CellTiter-Glo® assays revealed that HO showed higher cytotoxicity effect against HL-60 cell line especially at concentration of 1:10 and 1:5. Meanwhile, the MTT (3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay revealed that the higher cytotoxicity effect showed at 1:5, with the cell viabilities were around 40-65%. The nematicidal assay discovered that HO at concentration of 1:5 showed higher activities compare to other concentrations with percentage viability of 70%. These studies have shown that HO shows cytotoxic effect against HL-60 cell lines, and moderate activity against S. feltiae as well.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2497-2497
Author(s):  
Andrew P. Mone ◽  
John C. Byrd

Abstract Leflunomide is a commercially available immunosuppressive agent approved for the treatment of rheumatoid arthritis. The compound is administered orally and is rapidly converted to the active compound A77 1726. The half-life of A77 1726 is long, with values reported as 10–15 days. Steady state plasma concentrations, in the treatment of rheumatoid arthritis, approach 250 μM. The proposed mechanism of A77 1726 is a reduction in lymphocyte proliferation due to inhibition of de novo pyrimidine synthesis and inhibition of tyrosine kinases. Given the need for chemotherapeutics with activity against neoplastic B-cell diseases that possess favorable pharmacokinetic and side effect profiles, we examined the in vitro antiproliferative effect of A77 1726 upon neoplastic B-cell lines, and its in vitro cytotoxic effect upon primary CLL cells. Raji, Ramos, 697, WaC3CD5 and Daudi B-cell lines were treated with A77 1726 (0, 1, 10, 50, 100, 200 and 300 μM) for 24, 48 and 96 hrs in RPMI media supplemented with 10% fetal bovine serum. The antiproliferative effect of was determined using the MTT assay. A77 1726 IC50 values for each cell line are: Raji (36 μM), Ramos (18 μM), 697 (29 μM), WaC3CD5 (83 μM) and Daudi (13 μM). Cell cycle analysis of Raji cells using propidium iodide (PI) staining with FACS analysis, showed a reduction of the fraction of cells in G2 from 19 % to 4.9 % with A77 1726 (200 μM) treatment. A77 1726 binds to albumin, diminishing its effective concentration. Human albumin (3 gm/dl) reduced the effectiveness of A77 1726 (200 μM) upon both Raji and WaC3CD5 cell lines. In the presence of albumin, the number of viable Raji cells increased from 32% to 74%, and for WaC3CD5 cells the value increased from 19% to 78%, as compared to the untreated control cells. Both cell lines multiplied slower in the presence of human albumin, thus the observed antiproliferative effect of A77 1726 was proportionally reduced. A77 1726 reduces de novo pyrimidine synthesis by inhibiting the enzyme dihydroorotate dehydrogenase. The reduction in de novo pyrimidine synthesis can be surmounted by the exogenous addition of uridine to the culture media. The Raji and WaC3CD5 cell lines were incubated with A77 1726 with and without uridine to determine the role of pyrimidine synthesis in A77 1726′s antiproliferative effect upon the cell lines. For the Raji cell line, addition of 50 μM uridine to A77 1726 (200 μM) treated cells increased the number of viable cells from 22% to 62% of the untreated control. For the WaC3CD5 cell line, the addition of uridine did not decrease the antiproliferative effect of A77 1726. These data agree with prior studies that indicated an antiproliferative effect of A77 1726 beyond its inhibition of de novo pyrimidine synthesis. CLL cells do not reproduce in vitro; however, we hypothesized that the pyrimidine-independent effect of A77 1726 may be cytotoxic to CLL cells in vitro. Five negatively selected primary CLL samples were treated with A77 1726 (0, 50, 100, 200 and 300 μM) for 120 hrs and cell viability was determined with the MTT assay. Significant (greater than 40 % of control value) cytotoxicity occurred with 200 μM A77 1726 in 3 of 5 samples. Treatment with 300 μM A77 1726 led to significant killing in all the samples; the mean viability, as compared to untreated control, was 36% (SD 21, N=5). Addition of uridine did not reverse the observed cytotoxic effect of A77 1726 upon CLL cells. Annexin V-FITC/PI staining with FACS analysis confirmed the cytotoxic effect of A77 1726 on CLL cells. Further study of leflunomide in animal models of neoplastic B-cell disorders is warranted.


2017 ◽  
Vol 63 (1) ◽  
pp. 141-145
Author(s):  
Yuliya Khochenkova ◽  
Eliso Solomko ◽  
Oksana Ryabaya ◽  
Yevgeniya Stepanova ◽  
Dmitriy Khochenkov

The discovery for effective combinations of anticancer drugs for treatment for breast cancer is the actual problem in the experimental chemotherapy. In this paper we conducted a study of antitumor effect of the combination of sunitinib and bortezomib against MDA-MB-231 and SKBR-3 breast cancer cell lines in vitro. We found that bortezomib in non-toxic concentrations can potentiate the antitumor activity of sunitinib. MDA-MB-231 cell line has showed great sensitivity to the combination of bortezomib and sunitinib in vitro. Bortezomib and sunitinib caused reduced expression of receptor tyrosine kinases VEGFR1, VEGFR2, PDGFRa, PDGFRß and c-Kit on HER2- and HER2+ breast cancer cell lines


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.


2020 ◽  
Vol 45 (4) ◽  
pp. 423-428
Author(s):  
Ali Mert Özgönül ◽  
Aycan Aşık ◽  
Burak Durmaz ◽  
Ramin Aslaminabad ◽  
Cumhur Gündüz ◽  
...  

AbstractObjectivesRecently, phenolic compounds (quercetin, kaempferol, ellagic acid (EA), and myricetin) as natural sources have been suggested to be used for treatment and chemoprevention of prostate cancer. Since rosehip includes the above molecules in high concentration, we set out to investigate possible anti-proliferative effect of rosehip tea on the prostate cancer cell line.MethodsThe flavonol content of rosehip tea prepared at different temperatures and time intervals was determined first and then the antiproliferative effect of tea samples was established by adding tea samples to the prostate cancer cell line (VCaP and LNCaP).ResultsQuercetin was more effective in LNCaP cell than in VCaP cell (IC50 = 20 and 200 μM, respectively). The boiled fruit shredded at minute 7 showed the highest levels of quercetin, EA and kaempferol and the boiled fruit at minute 7 had the highest levels of kaempferol and EA. The tea samples were prepared in concentrations relevant to their IC50 values, added to the VCaP and LNCaP cell lines. The antiproliferative effect of rosehip tea on VCaP cells was slightly greater than that of LNCaP cells.ConclusionEach of the flavonols exhibits an antiproliferative effect. Our data clearly indicated that rosehip as a natural source of all flavonols had an antiproliferative effect on androgen-sensitive prostate cancer. Now that it is important to use natural sources in cancer, rosehip seems to be a promising natural product to be used to treat the prostate illness.


Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 502
Author(s):  
Filipe Almeida ◽  
Andreia Gameiro ◽  
Jorge Correia ◽  
Fernando Ferreira

Feline mammary carcinoma (FMC) is the third most common type of neoplasia in cats, sharing similar epidemiological features with human breast cancer. In humans, histone deacetylases (HDACs) play an important role in the regulation of gene expression, with HDAC inhibitors (HDACis) disrupting gene expression and leading to cell death. In parallel, microtubules inhibitors (MTIs) interfere with the polymerization of microtubules, leading to cell cycle arrest and apoptosis. Although HDACis and MTIs are used in human cancer patients, in cats, data is scarce. In this study, we evaluated the antitumor properties of six HDACis (CI-994, panobinostat, SAHA, SBHA, scriptaid, and trichostatin A) and four MTIs (colchicine, nocodazole, paclitaxel, and vinblastine) using three FMC cell lines (CAT-MT, FMCp, and FMCm), and compared with the human breast cancer cell line (SK-BR-3). HDACis and MTIs exhibited dose-dependent antitumor effects in FMC cell lines, and for all inhibitors, the IC50 values were determined, with one feline cell line showing reduced susceptibility (FMCm). Immunoblot analysis confirmed an increase in the acetylation status of core histone protein HDAC3 and flow cytometry showed that HDACis and MTIs lead to cellular apoptosis. Overall, our study uncovers HDACis and MTIs as promising anti-cancer agents to treat FMCs.


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Parisa Taherzadeh-Soureshjani ◽  
Mohammad Chehelgerdi

Abstract Background Breast cancer (BC), as the most widely recognized disease in women worldwide, represents about 30% of all cancers impacting women. This study was aimed to synthesize Cu2O nanoparticles from the cystoseira myrica algae (CM-Cu2O NPs) assess their antimicrobial activity against pathogenic bacteria and fungi. We evaluated the expression levels of lncRNAs (MALAT1 and GAS5) and apoptosis genes (p53, p27, bax, bcl2 and caspase3), their prognostic roles. Methods In this study, CM-Cu2O NPs synthesized by cystoseira myrica algae extraction used to evaluate its cytotoxicity and apoptotic properties on MDA-MB-231, SKBR3 and T-47D BC cell lines compared to HDF control cell line. The CM-Cu2O NPs was characterized by UV–Vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Transmission electron microscopy (TEM) and Scanning electron microscopy (SEM). The antimicrobial activity of CM-Cu2O NPs was assessed against pathogenic bacteria, staphylococcus aureus (S. aureus) PTCC 1112 bacteria as a standard gram-positive bacteria and pseudomonas aeruginosa (P. aeruginosa) PTCC 1310 as a standard gram-negative bacterium. Expression profile of MALAT1 and GAS5 lncRNAs and apoptosis genes, i.e., p27, bax, bcl2 and caspase3 genes, were calculated utilizing qRT-PCR. The changes in the expression levels were determined using the DDCT method. Results MALAT1 was upregulated in MDA-MB-231, SKBR3 and T-47D BC (p < 0.01), while GAS5 was downregulated in SKBR3 and T-47D cell lines tested compared with HDF control cell line (p < 0.05) was found. The results revealed that, p27, bax and caspase3 were significantly upregulated in BC cell lines as compared with normal cell line. Bcl2 expression was also significantly increased in MDA-MB-231 and T47D cell lines compared with normal cell line, but bcl2 levels were downregulated in SKBR3 cell line. Conclusions Our results confirm the beneficial cytotoxic effects of green-synthesized CM-Cu2O NPs on BC cell lines. This nanoparticle decreased angiogenesis and induces apoptosis, so we conclude that CM-Cu2O NPs can be used as a supplemental drug in cancer treatments. Significantly, elevated circulating lncRNAs were demonstrated to be BC specific and could differentiate BC cell lines from the normal cell lines. It was demonstrated that lncRNAs used in this study and their expression profiles can be created as biomarkers for early diagnosis and prognosis of BC. Further studies utilizing patients would give recognizable identification of lncRNAs as key players in intercellular interactions.


2015 ◽  
Vol 7 ◽  
pp. BIC.S19079 ◽  
Author(s):  
Seyedmehdi Nourashrafeddin ◽  
Mehdi Dianatpour ◽  
Mahmoud Aarabi ◽  
Maryam Beigom Mobasheri ◽  
Golnesa Kazemi-oula ◽  
...  

Breast cancer is one of the most common causes of cancer death in women; therefore, the study of molecular aspects of breast cancer for finding new biomarkers is important. Recent studies have shown that WW domain-binding protein 2 (WBP2) is important for the oncogenic property of breast cancer. WWP2 N-terminal-like ( WBP2NL) is a testis-specific signaling protein that induces meiotic resumption and oocyte activation events. Our previous study revealed that WBP2NL gene expression is elevated in actively dividing cells and it might be associated with cellular proliferation and tumorigenic process. However, the clinical relevance and importance of WBP2NL gene in cancer has not been understood yet. Therefore, we were interested in analyzing the expression of WBP2NL gene in human breast cancer tissues and breast cancer cell lines, for the first time. We used reverse transcription-polymerase chain reaction (RT-PCR) and semi-nested RT-PCR to evaluate the expression of WBP2NL in malignant breast cancer and adjacent noncancerous tissue (ANCT) samples, as well as MCF-7 and MDA-MB-231 cell lines. The WBP2NL gene was expressed in 45 out of 50 (90%) breast cancer tissues and overexpressed in the MDA-MB-231 cell line. We suggest that WBP2NL may play roles in breast cancer activation maybe through binding to a group I WW domain protein. The elevated expression of WBP2NL gene in breast cancer and MDA-MB-231 cell line leads us to suggest that WBP2NL might be considered as a novel prognostic factor for early diagnosis of breast cancer.


Author(s):  
Fatma Kubra Ata ◽  
Serap Yalcin

Background: Chemotherapeutics have been commonly used in cancer treatment. Objective: In this study, the effects of Cisplatin, 5-fluorouracil, Irinotecan, and Gemcitabine have been evaluated on two-dimensional (2D) (sensitive and resistance) cell lines and three dimensional (3D) spheroid structure of MDA-MB-231. The 2D cell culture lacks a natural tissue-like structural so, using 3D cell culture has an important role in the development of effective drug testing models. Furthermore, we analyzed the ATP Binding Cassette Subfamily G Member 2 (ABCG2) gene and protein expression profile in this study. We aimed to establish a 3D breast cancer model that can mimic the in vivo 3D breast cancer microenvironment. Methods: The 3D spheroid structures were multiplied (globally) using the three-dimensional hanging drop method. The cultures of the parental cell line MDA-MB-231 served as the controls. After adding the drugs in different amounts we observed a clear and well-differentiated spheroid formation for 24 h. The viability and proliferation capacity of 2D (sensitive and resistant) cell lines and 3D spheroid cell treatment were assessed by the XTT assay. Results: Cisplatin, Irinotecan, 5-Fu, and Gemcitabine-resistant MDA-MB-231 cells were observed to begin to disintegrate in a three-dimensional clustered structure at 24 hours. Additionally, RT-PCR and protein assay showed overexpression of ABCG2 when compared to the parental cell line. Moreover, MDA-MB-231 cells grown in 3D showed decreased sensitivity to chemotherapeutics treatment. Conclusion: More resistance to chemotherapeutics and altered gene expression profile was shown in 3D cell cultures when compared with the 2D cells. These results might play an important role to evaluate the efficacy of anticancer drugs, explore mechanisms of MDR in the 3D spheroid forms.


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