Comparison of Selenic Acid and Pyruvic Acid-Loaded Silver Nanocarriers Impact on Colorectal Cancer Viability.

Colorectal cancer (CRC) is a leading cause of morbidity and death worldwide. As current cancer drugs are ineffective, new solutions are being sought in other fields, including nanoscience. Similarly, silver nanoparticles play an important role in the pharmaceutical industry as they act as anti-cancer agents with less harmful effects and are usually 1 to 100 nm in size. Selenic acid (SA) and pyruvic acid (PA) are involved in various metabolic pathways in cancer. For this reason, we decided to detect their influence on colorectal cancer using silver-based (Ag) nanocarriers. DLS, Zetasizer, SEM and UV-Vis analyses were used to characterize AgSA and AgPA. A UV spectrophotometer was used to analyze the release of the NPs. MTT analyses were used to measure the viability of HCT116 and HUVEC cells, and IC50 values were calculated using GraphPad Prism. The indicated dosage and particle size of AgSA NPs proved to be suitable for cytotoxicity. Moreover, injection of these nanoparticles into non-cancer cells proved safe due to their minimal toxicity. In contrast, the AgPA NPs have no cytotoxicity and induce proliferation of HCT116 cells. Finally, only the synthesised AgSA nanoparticles could be used for advanced cancer therapy, which is both inexpensive and has minimal side effects.

Effective drug combinations of betulinic acid and ceranib-2 loaded Zn:MnO2 doped-polymeric nanocarriers against PC-3 prostate cancer cells.

The development of theranostic nanocarriers with synergistic drug combinations has received considerable attention due to their improved pharmaceutical activity. Herein, we reported an investigation about the in-vitro anticancer activity of ceranib-2 (Cer), betulinic acid (BA), and the combination of betulinic acid and ceranib-2 (BA-Cer) against PC-3 prostate cancer cells. For this purpose, first we designed a suitable nanocarrier using a novel Zn:MnO2 nanocomposite (NCs) and gallic acid (GA)-polylactic acid (PLA)-Alginate polymeric shell with nanoscale particle size and good stability. Chemical statements, morphology, and physicochemical properties of the nanocarrier have been illuminated with advanced characterization techniques. According to the transmission electron microscopy (TEM) results, Zn:MnO2 NCs had a spherical and monodispersed morphology with a 2.03 ± 0.67 nm diameter. Moreover, vibrating-sample magnetometer (VSM) results showed that Zn:MnO2 had paramagnetic properties with a saturation magnetization (Ms) value of 1.136 emu/g. Additionally, the in-vitro cytotoxic effects of the single and binary drugs loaded Zn:MnO2-doped polymeric nanocarriers against PC-3 prostate cancer cells were investigated. According to the results, there was no significant cytotoxic effect of free BA and Cer against PC-3 prostate cancer cells. However, BA/Zn:MnO2@GA-PLA-Alginate NCs, BA-Cer/Zn:MnO2 @GA-PLA-Alginate NCs and free BA-Cer had IC50 values of 6.498, 7.351, and 18.571 µg/mL, respectively. Consequently, BA-Cer/Zn:MnO2@GA-PLA-Alginate is a nanocarrier with good stability, enhanced drug loading and release capacity for hydrophobic drugs, as well as being used as both imaging and treatment agent due to its magnetic properties. Furthermore, BA and Cer drug combination showed great promise in prostate cancer therapy which is known to be resulted high drug resistance. We strongly believed that this work could lead to an investigation of the molecular mechanisms of BA-mediated cancer theapy.

DNA groove binder and significant cytotoxic activity on human colon cancer cells: Potential of a dimeric zinc (II) phthalocyanine derivative.

The interaction of a multi-component system consisting of benzene-1,4-diyldimethanimine-bridged dimeric zinc-phthalocyanine groups (4OMPCZ) with calf thymus DNA (ct-DNA) was investigated using UV-Vis absorption, fluorescence emission spectroscopy methods, and viscosity measurements. The binding constant, Kb, which is an important parameter to gain information about the binding mode, was found as 9.7 × 107 M-1 from the UV-Vis absorption studies. Another important spectrophotometric tool is competitive displacement assays with Ethidium bromide and Hoechst 33342. Through this experiment, a higher KSV value was obtained with Hoechst for the phthalocyanine derivative, 4OMPCZ, and the ct-DNA complex than with ethidium bromide. Additionally, molecular docking studies were conducted to calculate the theoretical binding constant and visualize the interactions of 4OMPCZ with a model DNA. According to docking results, although the interactions are mainly located in the major groove of the DNA helix, due to the wrapping, these interactions can also be extended to the minor groove of the DNA. Spectrophotometric, molecular docking, and viscosity studies revealed that the interaction of 4OMPCZ with DNA is likely to be via the major and minor grooves. The in vitro cytotoxic activity of 4OMPCZ was evaluated by MTT assay on human colon cancer cells (HT29) after 72 h of treatment. 4OMPCZ indicated significant cytotoxic activity when stimulated with UV light compared to the standard chemotherapy drugs, fluorouracil (5-FU), and cisplatin on HT29 colon cancer cells. The IC50 value of 4OMPCZ displayed considerably lower concentrations compared to the standard drugs, 5-FU, and cisplatin.

The Novel 5-Fluorouracil Loaded Ruthenium-based Nanocarriers Enhanced Anticancer and Apoptotic Efficiency while Reducing Multidrug Resistance in Colorectal Cancer Cells.

Recently, nanocarriers have been made to eliminate the disadvantages of chemotherapeutic agents by nanocarriers. Nanocarriers show their efficacy through their targeted and controlled release. In this study, 5-fluorouracil (5FU) was loaded into ruthenium (Ru)-based nanocarrier (5FU-RuNPs) for the first time to eliminate the disadvantages of 5FU, and its cytotoxic and apoptotic effects on HCT116 colorectal cancer cells were compared with free 5FU. 5FU-RuNPs with a size of approximately 100 nm showed a 2.61-fold higher cytotoxic effect compared to free 5FU. Apoptotic cells were detected by Hoechst/propidium iodide double staining, and the expression levels of BAX/Bcl-2 and p53 proteins, in which apoptosis occurred intrinsically, were revealed. In addition, 5FU-RuNPs was also found to reduce multidrug resistance (MDR) according to BCRP/ABCG2 gene expression levels. When all the results were evaluated, the fact that Ru-based nanocarriers alone did not cause cytotoxicity proved that they were ideal nanocarriers. Moreover, 5FU-RuNPs did not show any significant effect on the cell viability of normal human epithelial cell lines BEAS-2B. Consequently, the 5FU-RuNPs synthesized for the first time may be ideal candidates for cancer treatment because they can minimize the potential drawbacks of free 5FU.

Evaluation of anticancer effects of carboplatin-gelatin nanoparticles in different sizes synthesized with newly self-assembly method by exposure to IR light.

Carboplatin (CP), a platinum analog, is one of the most widely used chemotherapeutic agents in the treatment of colorectal cancer. Although platinum-based drugs are quite effective in anticancer treatments, their use in a wide spectrum and effective treatment possibilities are limited due to their systemic side effects and drug resistance development. In recent years, studies have focused on increasing the therapeutic efficacy of platinum-based drugs with drug delivery systems. Gelatin, a protein, obtained by the hydrolysis of collagen, is a biocompatible and biodegradable material that can be used in nano drug delivery systems. In this study, CP-loaded gelatin-based NPs (CP-NPs) were exposed to IR light in different temperatures at 30, 35, 40, 45, and 50 °C and characterized by FESEM-EDX, FTIR, UV-Vis, DLS. Accordingly, we synthesized gelatin-based CP-NPs of different sizes between 10-290 nm by exposure to IR. We found that CP-NPs-50, 16 nm nano-sized, obtained at 50 °C had the most cytotoxicity and was 2.2 times more effective than the free drug in HCT 116 colon cancer cells. Moreover, we showed that the cytotoxicity of CP-NPs-50 in normal HUVEC cells was lower. Additionally, we demonstrated that CP-NPs enhanced apoptotic activity while not developing MDR1-related resistance in colon cancer cells. In this study, for the first time drug loaded gelatin-based nanoparticles were synthesized in different sizes with a newly self-assembly method by exposing them to infrared light at different temperatures and their anticancer effects were evaluated subsequently.

Selective Cytotoxic Effects of 5-Trifluoromethoxy-1H-indole-2,3-dione 3-Thiosemicarbazone Derivatives on Lymphoid-originated Cells.

AIM: The present study aims to identify the anticancer effect of novel 1H-indole-2,3-dione 3- thiosemicarbazone derivatives. These compounds could be promising anticancer agents in leukemia treatment. BACKGROUND: Conventional chemotherapeutic agents accumulate in both normal and tumor cells due to nonspecificity. For effective cancer treatment, new drugs need to be developed to make chemotherapeutics selective for cancer cells. The ultimate goal of cancer treatment is to reduce systemic toxicity and improve the quality of life. METHODS: In this study, the anticancer effects of 5-trifluoromethoxy-1H-indole-2,3-dione 3-thiosemicarbazone derivatives (A-L) were investigated in chronic myelogenous leukemia K562, Burkitt's lymphoma P3HR1, acute promyelocytic leukemia HL60 cells, and vincristine-resistant sublines of K562 and P3HR1 cells. Additionally, the compounds were tested on lymphoid-derived cells from ALL patients. In order to investigate the particular mechanism of death caused by the cytotoxic effects of the compounds, immunohistochemical caspase 3 staining was performed in P3HR1 cells, and the resulting apoptotic activities were demonstrated. RESULTS: All tested compounds have been found to have cytotoxic effects against lymphoma cells at submicromolar concentrations (IC50= 0.89-1.80 µM). Most compounds show significant selectivity for the P3HR1 and P3HR1 Vin resistance. The most effective and selective compound is 4-bromophenyl substituted compound I (IC50=0.96 and 0.89 µM). Cyclohexyl and benzyl substituted compounds D and E have also been found to have cytotoxic effects against K562 cell lines (IC50=2.38 µM), while the allyl substituted compound C is effective on all cell lines (IC50=1.13-2.21 µM). 4-Fluorophenyl substituted F compound has been observed to be effective on all cells (IC50=1.00-2.41 µM) except K562 cell. Compound C is the only compound that shows inhibition of HL-60 cells (IC50= 1.13 µM). Additionally, all compounds exhibited cytotoxic effects on lymphoidderived cells at 1µM concentration. These results are in accordance with the results obtained in lymphoma cells. CONCLUSION: All compounds tested have submicromolar concentrations of cytotoxic effects on cells. These compounds hold potential for use in future treatments of leukemia.

Cytotoxic Effects of Some Flavonoids and Imatinib on the K562 Chronic Myeloid Leukemia Cell Line: Data Analysis Using the Combination Index Method

Background: Flavonoids are natural compounds with antioxidant, anticarcinogenic, and anti-inflammatory effects. Aims: To determine the cytotoxic effects of flavonoids and drug resistance related to P-gp on K562 human chronic myeloid leukemia cells. We also aimed to evaluate the therapeutic potential of imatinib and flavonoid combinations. Study Design: Cell culture study. Methods: In this study, K562 cells were treated with apigenin, luteolin, 5-desmethyl sinensetin and the anticancer drug imatinib mesylate. The effect of flavonoids on K562 cell proliferation was detected using the 3-(4,5-dimethylthiazolyl)2,5­diphenyl­tetrazolium bromide assay. Concentrations of apigenin, luteolin, and 5-desmethyl sinensetin ranging from 25 to 200 µM and of imatinib from 5 to 50 µM administered for 72 h were studied. Apoptosis/necrosis and P-gp activity were measured using flow cytometry. The combined effects of different concentrations of flavonoids with imatinib were evaluated according to combination index values calculated using CompuSyn software. Results: In our study, the IC50 values for apigenin, luteolin, and 5-desmethyl sinensetin were found to be 140 µM, 100 µM, and >200 µM, respectively. Luteolin (100 µM) had the highest cytotoxic activity of these flavonoids. These results were statistically significant (p<0.05). Among the flavonoids studied, the combination of luteolin and imatinib was the most effective and is therefore recommended for its cytotoxic activity in the K562 cell line. After 72 h of incubation at their respective IC50 concentrations, all flavonoids were associated with an apoptosis rate of approximately 50%. P-glycoprotein activity was increased in all groups. Combination treatment may provide better outcomes in terms of cytotoxicity and thus reduce the dosages of imatinib used. Conclusion: The combination of some flavonoids and imatinib mesylate may increase the cytotoxic effect; However, the antagonistic effect should be considered in combined use on k562 cells.