scholarly journals Preparation, Characterization, and Anticancer Effects of Capsaicin-Loaded Nanoliposomes

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 3995
Author(s):  
Ali Al-Samydai ◽  
Walhan Alshaer ◽  
Emad A. S. Al-Dujaili ◽  
Hanan Azzam ◽  
Talal Aburjai
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Therapeutic Potential ◽  
Drug Loading ◽  
Cell Viability Assay ◽  
Viability Assay ◽  
Anticancer Effects ◽  
Pharmacokinetic Properties ◽  
Quantitative Analyses

Background: Medicinal plants have proven their value as a source of molecules with therapeutic potential, and recent studies have shown that capsaicin has profound anticancer effects in several types of human cancers. However, its clinical use is handicapped due to its poor pharmacokinetics. This study aims to enhance capsaicin’s pharmacokinetic properties by loading the molecule into nanoliposomes model and testing its anticancer activity. Methods: Nanoliposomes were prepared using the thin-film method, and characteristics were examined followed by qualitative and quantitative analyses of encapsulation efficiency and drug loading using HPLC at different lipid/capsaicin ratios. Cell viability assay (MTT) was used to determine IC50. Results: Capsaicin-loaded nanoliposomes showed optimum characteristics of morphology, particle size, zeta potential, and stability. In vitro anticancer activity of capsaicin and capsaicin-loaded nanoliposomes were compared against MCF7, MDA-MB-231, K562, PANC1, and A375 cell lines. Capsaicin-loaded nanoliposomes showed significant improvement in anticancer activity against cancers cell lines studied (p < 0.001), with increased selectivity against cancer cells compared to capsaicin. Conclusion: The encapsulated capsaicin nanoliposomes produced an improvement in pharmacokinetics properties, enhancing the anticancer activity and selectivity compared with capsaicin. This model seems to offer a potential for developing capsaicin formulations for the prevention and treatment of cancer.

scholarly journals Synthesis, Characterization, and Anticancer Activity of New Benzofuran Substituted Chalcones

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Demet Coşkun ◽  
Suat Tekin ◽  
Süleyman Sandal ◽  
Mehmet Fatih Coşkun
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Antitumor Activities ◽  
Cell Viability Assay ◽  
Anticancer Properties ◽  
Viability Assay ◽  
Diphenyltetrazolium Bromide ◽  
Antitumor Properties ◽  
Mcf 7

Benzofuran derivatives are of great interest in medicinal chemistry and have drawn considerable attention due to their diverse pharmacological profiles including anticancer activity. Similarly, chalcones, which are common substructures of numerous natural products belonging to the flavonoid class, feature strong anticancer properties. A novel series of chalcones, 3-aryl-1-(5-bromo-1-benzofuran-2-yl)-2-propanones propenones (3a–f), were designed, synthesized, and characterized.In vitroantitumor activities of the newly synthesized (3a–f) and previously synthesized (3g–j) chalcone compounds were determined by using human breast (MCF-7) and prostate (PC-3) cancer cell lines. Antitumor properties of all compounds were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell viability assay for the tested chalcone compounds was performed and thelog⁡IC50values of the compounds were calculated after 24-hour treatment. Our results indicate that the tested chalcone compounds show antitumor activity against MCF-7 and PC-3 cell lines (p<0.05).

scholarly journals Synthesis of Novel FTY720 Analogs with Anticancer Activity through PP2A Activation

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2750 ◽  
Author(s):  
Jitendra Shrestha ◽  
Sung Ki ◽  
Sang Shin ◽  
Seon Kim ◽  
Joo-Youn Lee ◽  
...  
Keyword(s):  
Cell Viability ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Sphingosine Kinase ◽  
Basic Structure ◽  
Docking Study ◽  
Cell Viability Assay ◽  
Viability Assay ◽  
Anticancer Effects ◽  
Pp2a Activation

FTY720 inhibits various cancers through PP2A activation. The structure of FTY720 is also used as a basic structure for the design of sphingosine kinase (SK) inhibitors. We have synthesized derivatives using an amide chain in FTY720 with a phenyl backbone, and then compounds were screened by an MTT cell viability assay. The PP2A activity of compound 7 was examined. The phosphorylation levels of AKT and ERK, downstream targets of PP2A, in the presence of compound 7, were determined. Compound 7 may exhibit anticancer effects through PP2A activation rather than the mechanism by inhibition of SK1 in cancer cells. In the docking study of compound 7 and PP2A, the amide chain of compound 7 showed an interaction with Asn61 that was different from FTY720, which is expected to affect the activity of the compound.

P13.08 Novel Thioridazine derivates: Antiproliferative and apoptosis-inducing activity on glioblastoma cells in vitro

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii34-ii34
Author(s):  
S G Schwab ◽  
K Sarnow ◽  
E Alme ◽  
R Goldbrunner ◽  
H Bjørsvik ◽  
...  
Keyword(s):  
Imaging System ◽  
Therapeutic Potential ◽  
Flow Cytometric Analysis ◽  
Annexin V ◽  
Therapeutic Effects ◽  
Cell Viability Assay ◽  
Selective Cytotoxicity ◽  
Viability Assay

Abstract BACKGROUND Although withdrawn from the market due to cardiotoxicity, we have shown that the antipsychotic drug Thioridazine shows chemosensitizing effects in combination with Temozolomide (TMZ) for the treatment of glioblastoma multiforme (GBM). Based on our prior observations, the aim of the presented project was through medicinal chemistry, to design and synthesize new compounds based on Thioridazines tricyclic structure, and to determine their therapeutic potential. MATERIAL AND METHODS Fourteen compounds were synthesized where variations were made within the tricyclic side chains. The newly synthesized compounds were screened for therapeutic efficacy with or without TMZ using a WST-1 cell viability assay as well as a real-time imaging system (IncuCyte). Tests were performed on both monolayer cell cultures, as well as on glioma stem cell spheroids (GSC). The therapeutic effects were also studied on human astrocytes (NHA) as well as on rat brain organoids (BO). Annexin V/propidium iodide (PI) double staining followed by flow cytometric analysis was performed after 48 hours of treatment. RESULTS Following an extensive screening, we identified two novel compounds (EA01 and EA02) that at concentrations of 4 and 9.5 µM showed a strong cytotoxicity on GBM cell lines (U-87 MG p&lt;0,0001, U251 p&lt;0,0001, LN18 p=0,0004) as well as on glioma stem cells (GSC) (P3 p&lt;0,0001) compared to NHA and BOs respectively. Also, when BOs were confronted with GSC spheres in an invasion assay, a selective cytotoxicity was observed in the GSCs. Mechanistically, we show that both compounds induce apoptosis in the GBM cells. Moreover, intravenous delivery of increasing concentrations of EA01 and EA02 revealed no toxicity in animals at concentrations up to 21 mg/kg. CONCLUSION We have developed two new tricyclic therapeutic compounds that show a strong selective cytotoxicity in GBM cells with limited systemic toxicity in animals. Ongoing studies are investigating the therapeutic potential of EA01 and EA02 in orthotopic xenografts in vivo.

scholarly journals A Novel Synthesis of Fe3O4@SiO2@Au@Porous SiO2 Structure for NIR Irradiation-Induced DOX Release and Cancer Treatment

Dose-Response ◽  
2020 ◽  
Vol 18 (1) ◽  
pp. 155932582090666
Author(s):  
Meng Yang ◽  
Wenhua Yang ◽  
Liang Chen ◽  
Mingjian Ding ◽  
Chenhao Li ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Near Infrared ◽  
Drug Loading ◽  
Thermal Conversion ◽  
Au Nanoparticle ◽  
Cell Viability Assay ◽  
Viability Assay ◽  
Transmission Electron ◽  
Adsorption Desorption

Doxorubicin (DOX) alone or in combination has been widely used for numerous cancers, including breast, lung, bladder, and so on. In this article, a core/shell/shell structured Fe3O4@SiO2@Au@porous SiO2 particles for the drug delivery and release of DOX was demonstrated, with the aid of near-infrared irradiation. Fe3O4 was used to direct the transportation and delivery of the drug-loaded composite to the target tissues and organs under an external magnetic field, the first layer of SiO2 was used for Au nanoparticle attachment, Au acted as the agent for light–thermal conversion, and the porous SiO2 was used to load DOX. The morphology of the nanoparticles was studied by transmission electron microscopy, and the porous structure was characterized by N2 adsorption/desorption curves. The drug delivery system displayed high drug loading capacity, and the release behavior was largely impacted by the environmental pH. Furthermore, the cytotoxicity of Fe3O4@SiO2@Au@porous SiO2 and DOX loaded Fe3O4@SiO2@Au@porous SiO2 was studied through in vitro 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell viability assay.

scholarly journals β-Adrenergic Receptor Inhibitor and Oncolytic Herpesvirus Combination Therapy Shows Enhanced Antitumoral and Antiangiogenic Effects on Colorectal Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiali Hu ◽  
Cuiyu Chen ◽  
Ruitao Lu ◽  
Yu Zhang ◽  
Yang Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Oncolytic Virus ◽  
Caspase 3 ◽  
Therapeutic Potential ◽  
Tumor Regression ◽  
Oncolytic Viruses ◽  
Cell Viability Assay ◽  
Viability Assay

Oncolytic viruses (OVs) are considered a promising therapeutic alternative for cancer. However, despite the development of novel OVs with improved efficacy and tumor selectivity, their limited efficacy as monotherapeutic agents remains a significant challenge. This study extended our previously observed combination effects of propranolol, a nonselective β-blocker, and the T1012G oncolytic virus into colorectal cancer models. A cell viability assay showed that cotreatment could induce synergistic killing effects on human and murine colorectal cell lines. Moreover, cotreatment caused sustained tumor regression compared with T1012G monotherapy or propranolol monotherapy in human HCT116 and murine MC38 tumor models. The propranolol activity was not via a direct effect on viral replication in vitro or in vivo. Western blotting showed that cotreatment significantly enhanced the expression of cleaved caspase-3 in HCT116 and MC38 cells compared with the propranolol or T1012G alone. In addition, propranolol or T1012G treatment induced a 35.06% ± 0.53% or 35.49% ± 2.68% reduction in VEGF secretion in HUVECs (p &lt; 0.01/p &lt; 0.01). Cotreatment further inhibited VEGF secretion compared with the monotherapies (compared with propranolol treatment: 75.06% ± 1.50% decrease, compared with T1012G treatment: 74.91% ± 0.68%; p＜0.001, p &lt; 0.001). Consistent with the in vitro results, in vivo data showed that cotreatment could reduce Ki67 and enhance cleaved caspase 3 and CD31 expression in human HCT116 and murine MC38 xenografts. In summary, β-blockers could improve the therapeutic potential of OVs by enhancing oncolytic virus-mediated killing of colorectal cancer cells and colorectal tumors.

scholarly journals Effect of Metalloprotease Arazyme on the Expression of MMP2 and MMP9 Genes in Metastasis of Colon and Ovarian Cancer Cell Lines

Thrita ◽  
2020 ◽  
Vol 8 (2) ◽  
Author(s):  
Ghazaleh Amjadi ◽  
Kazem Parivar ◽  
Seyed Fazlollah Mousavi ◽  
Abbas Ali Imani Fooladi
Keyword(s):  
Ovarian Cancer ◽  
Cell Lines ◽  
The United States ◽  
Culture Cell ◽  
Bacterial Strains ◽  
Antitumor Effects ◽  
Cell Viability Assay ◽  
Viability Assay ◽  
Common Cancer

Background: After cardiovascular diseases, cancer is the main cause of death in the United States, and its prevalence is continually increasing. Ovarian cancer is a fetal and common cancer among women and is the eighth common cancer in Iran. Colorectal cancer is known as the second and fourth common cancer in Iranian women and men, respectively. Arazyme is a metalloprotease with strong antitumor effects on tumor cells. Objectives: This study aimed at studying the effect of metalloprotease arazyme in vitro on the expression of MMP2 and MMP9 genes, causing metastasis in ovarian and colon cancer. Methods: Bacterial strains and cell lines, the construction of an expression vector, and preparation of recombinant protein were done. Then, they were evaluated by Western blot, cell culture, cell viability assay, and reverse transcriptase-polymerase chain reaction. Results: The effects of arazyme on ovarian and colon cell lines were assessed by the MTT assay showing that the viability of cancer cells treated with arazyme decreased significantly in comparison with control cells. Also, RT-PCR showed that the expression of MMP2 and MMP9 genes decreased after treatment with arazyme, which was significant when compared to the results of pre-treatment. Conclusions: In this study, the results showed that the use of arazyme protein as a bacterial anti-protease can play a significant role in reducing the expression of metastatic genes. According to numerous studies on the role of bacterial proteases in the process of metastasis in recent years, this method can be considered as a therapeutic approach in reducing the metastatic process.

Sensitivity of Oncogenic KRAS-Expressing Cells to CDK9 Inhibition

2021 ◽  
pp. 247255522110088
Author(s):  
Lick Pui Lai ◽  
Viviane Brel ◽  
Kanika Sharma ◽  
Julia Frappier ◽  
Nadia Le-Henanf ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cell Lines ◽  
Specific Activity ◽  
Mammalian Target Of Rapamycin ◽  
Mouse Embryonic Fibroblast ◽  
Wild Type ◽  
Compound Library ◽  
Cell Viability Assay ◽  
Viability Assay

Oncogenic forms of KRAS proteins are known to be drivers of pancreatic, colorectal, and lung cancers. The goal of this study is to identify chemical leads that inhibit oncogenic KRAS signaling. We first developed an isogenic panel of mouse embryonic fibroblast (MEF) cell lines that carry wild-type RAS, oncogenic KRAS, and oncogenic BRAF. We validated these cell lines by screening against a tool compound library of 1402 annotated inhibitors in an adenosine triphosphate (ATP)-based cell viability assay. Subsequently, this MEF panel was used to conduct a high-throughput phenotypic screen in a cell viability assay with a proprietary compound library. All 126 compounds that exhibited a selective activity against mutant KRAS were selected and prioritized based on their activities in secondary assays. Finally, five chemical clusters were chosen. They had specific activity against SW620 and LS513 over Colo320 colorectal cancer cell lines. In addition, they had no effects on BRAFV600E, MEK1, extracellular signal-regulated kinase 2 (ERK2), phosphoinositide 3-kinase alpha (PI3Kα), AKT1, or mammalian target of rapamycin (mTOR) as tested in in vitro enzymatic activity assays. Biophysical assays demonstrated that these compounds did not bind directly to KRAS. We further identified the mechanism of action and showed that three of them have CDK9 inhibitory activity. In conclusion, we have developed and validated an isogenic MEF panel that was used successfully to identify RAS oncogenic or wild-type allele-specific vulnerabilities. Furthermore, we identified sensitivity of oncogenic KRAS-expressing cells to CDK9 inhibitors, which warrants future studies of treating KRAS-driven cancers with CDK9 inhibitors.

scholarly journals CBMT-09. THERAPEUTIC EFFECT OF INDUCTION OF POLYGLUTAMYLATION IN HIGH-DOSE METHOTREXATE THERAPY TO PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi34-vi34
Author(s):  
Kenji Fujimoto ◽  
Naoki Shinojima ◽  
Keishi Makino ◽  
Koichi Ichimura ◽  
Akitake Mukasa
Keyword(s):  
Cell Viability ◽  
Tumor Cells ◽  
Cell Lines ◽  
Therapeutic Response ◽  
Combined Effect ◽  
Occurrence Rate ◽  
High Dose ◽  
Cell Viability Assay ◽  
Viability Assay

Abstract BACKGROUND Polyglutamylation is a reversible protein modification with a high occurrence rate in tumor cells. Methotrexate (MTX) incorporated into cells is polyglutamylated and strongly binds to dihydrofolate reductase without competitive inhibition by leucovorin (LV). Tumor cells with high polyglutamylation levels are selectively killed, whereas normal cells with lower polyglutamylation are rescued by LV. In this study, we investigated the therapeutic response of PCNSL to HD-MTX therapy with LV rescue based on polyglutamylation status and evaluated the combined effect of MTX and the drugs which upregulated polyglutamylation of MTX. METHODS Among 113 consecutive PCNSL patients who underwent HD-MTX therapy in our department between 2001 and 2014, polyglutamylation was evaluated by immunostaining in 82 cases, with relationships between polyglutamylation and therapeutic response retrospectively examined. Human malignant lymphoma cell lines were used for in vitro and in vivo experiments. The association of polyglutamylation and the response to MTX with LV rescue was assessed in these cell lines. Histone-deacetylase inhibitor (HDACI) has been reported to induce polyglutamylation by elevating folpolyglutamate synthetase (FPGS) expression, so the effects of HDACIs on polyglutamylation were evaluated. Combined effects of MTX and HDACI were evaluated by cell viability assay and xenograft mouse models. RESULTS The complete response rate was significantly higher in the group with polyglutamylation than in the non-polyglutamylation group [58.1% (25/43) and 33.3% (13/39), respectively] (p < 0.05), and progression-free survival was also significantly increased in the group with polyglutamylation (p < 0.01). The combined effect of MTX and HDACI was significantly enhanced in cell viability assay in vitro (p< 0.05), in subcutaneous (p< 0.001) and intracranial tumor xenografts (p< 0.001). CONCLUSION These findings suggested that polyglutamylation could be a predictor of therapeutic response to HD-MTX therapy with LV rescue in PCNSL. Combined therapy with HD-MTX and HDACIs might represent a promising treatment for HD-MTX resistant intractable PCNSL.

EXTH-32. NOVEL THIORIDAZINE DERIVATES: ANTIPROLIFERATIVE AND APOPTOSIS-INDUCING ACTIVITY ON GLIOBLASTOMA CELLS IN VITRO

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi170-vi170
Author(s):  
Stephanie Schwab ◽  
Katharina Sarnow ◽  
Eirin Alme ◽  
Roland Goldbrunner ◽  
Hans-René Bjørsvik ◽  
...  
Keyword(s):  
Imaging System ◽  
Therapeutic Potential ◽  
Flow Cytometric Analysis ◽  
Annexin V ◽  
Therapeutic Effects ◽  
Cell Viability Assay ◽  
Selective Cytotoxicity ◽  
Viability Assay

Abstract BACKGROUND Although withdrawn from the market due to cardiotoxicity, we showed that the antipsychotic drug Thioridazine shows chemosensitizing effects in combination with Temozolomide (TMZ) for the treatment of glioblastoma multiforme (GBM). Based on our prior observations, the aim of this study was through medicinal chemistry, to design and synthesize new compounds based on Thioridazines tricyclic structure, and to determine their therapeutic potential. METHODS Fourteen compounds were synthesized where variations were made within the tricyclic side chains. The newly synthesized compounds were screened for therapeutic efficacy with or without TMZ using a WST-1 cell viability assay and real-time imaging system (IncuCyte). Tests were performed on both monolayer cell cultures, as well as on glioma stem cell spheroids (GSC). The therapeutic effects were also studied on human astrocytes (NHA) as well as on rat brain organoids (BO). Annexin V/propidium iodide (PI) double staining followed by flow cytometric analysis was performed after 48 hours of treatment. RESULTS Following an extensive screening, we identified two novel compounds (EA01 and EA02) that at concentrations of 4 and 9.5 µM showed a strong cytotoxicity on GBM cell lines (U-87 MG p&lt; 0,0001, U251 p&lt; 0,0001, LN18 p= 0,0004) as well as on glioma stem cells (GSC) (P3 p&lt; 0,0001) compared to NHA and BOs respectively. Also, when BOs were confronted with GSC spheres in an invasion assay, a selective cytotoxicity was observed in the GSCs. Mechanistically, we show that both compounds induce apoptosis in GBM cells. Moreover, intravenous delivery of increasing concentrations of EA01 and EA02 revealed no toxicity in animals at concentrations up to 21 mg/kg. CONCLUSION We developed two new tricyclic therapeutic compounds that show a strong selective cytotoxicity in GBM cells with limited systemic toxicity in animals. Ongoing studies are investigating the therapeutic potential of EA01 and EA02 in orthotopic xenografts in vivo.

Sign in / Sign up

Export Citation Format

Share Document