-
Environmental Science and Pollution... Mar 2020Multiple drug resistance and increased side effects due to allopathic drugs has warned scientific community with a global alarm to identify molecules from natural...
Radical scavenging and antiproliferative effect of novel phenolic derivatives isolated from Nerium indicum against human breast cancer cell line (MCF-7)-an in silico and in vitro approach.
Multiple drug resistance and increased side effects due to allopathic drugs has warned scientific community with a global alarm to identify molecules from natural sources to combat diseases with minimum or no side effects. The present investigation was aimed to identify and isolate secondary metabolites from traditionally used Nerium indicum using conventional column chromatography which led to the isolation of two compounds, C-I (fractions NB4f1) and C-II (fractions NC13b1). Further characterized, it is elucidated using spectral data and identified as N-(4-hydroxy-phenyl)-2-methoxy-2-phenyl-acetamide, molecular formula CHNO, and molecular weight 257.3 (C-I) and N-(4-hydroxy-phenyl)-2-phenyl-N-phenylacetyl-acetamide, molecular formula CHNO, and molecular weight 345.4 (C-II). Further, the isolated compounds were investigated using in silico approach by Autodock tool with four different proteins specific for cancer and in vitro assessed cell proliferation, and apoptosis against human breast cancer MCF 7 cell line. The results of the in silico model demonstrated potent binding affinity of both compounds with the proteins representing that the isolated molecules could be a drug of choice for cancer. Further, the isolated compounds revealed significant inhibition of cell proliferation (IC values 21 μg/mL for C-I, 19 μg/mL for C-II) with induced apoptosis with nuclear condensation effect on the MCF 7 cells in in vitro condition even at very low concentration. Compound treatment to MCF-7 cell line represented bright fetches indicating condensed chromatins and higher level of nuclear fragmentation with DAPI staining, indicating higher cell death due to induced apoptosis and confirmed using flow cytometry analysis representing inhibition of cell proliferation at S phase. Graphical abstract.
Topics: Antineoplastic Agents; Apoptosis; Breast Neoplasms; Cell Proliferation; Humans; MCF-7 Cells; Nerium; Phenols
PubMed: 31893365
DOI: 10.1007/s11356-019-07252-x -
Oxidative Medicine and Cellular... 2021Heterocycles containing thienopyrimidine moieties have attracted attention due to their interesting biological and pharmacological activities. In this research article,...
Heterocycles containing thienopyrimidine moieties have attracted attention due to their interesting biological and pharmacological activities. In this research article, we reported the synthesis of a series of new hybrid molecules through merging the structural features of chalcones and pyridothienopyrimidinones. Our results indicated that the synthesis of chalcone-thienopyrimidine derivatives from the corresponding thienopyrimidine and chalcones proceeded in a relatively short reaction time with good yields and high purity. Most of these novel compounds exhibited moderate to robust cytotoxicity against HepG2 and MCF-7 cancer cells similar to that of 5-fluorouracil (5-FU). The results indicated that IC of the two compounds ( and ) showed more potent anticancer activities against HepG2 and MCF-7 than 5-FU. An MTT assay and flow cytometry showed that only and had anticancer activity and antiproliferative activities at the G1 phase against MCF-7 cells, while six compounds (- and ) had cytotoxicity and cell cycle arrest at different phases against HepG2 cells. Their cytotoxicity was achieved through downregulation of Bcl-2 and upregulation of Bax, caspase-3, and caspase-9. Although all tested compounds increased oxidative stress increment of MDA levels and decrement of glutathione reductase (GR) activities compared to control, the , , and in HepG2 and and in MCF-7 achieved the target results. Moreover, there was a positive correlation between cytotoxic efficacy of the compound and apoptosis in both HepG2 ( = 0.531; = 0.001) and MCF-7 ( = 0.219; = 0.349) cell lines. The results of molecular docking analysis of into the binding groove of Bcl-2 revealed relatively moderate binding free energies compared to the selective Bcl-2 inhibitor, DRO. Like venetoclax, compounds showed 2 violations from Lipinski's rule. However, the results of the ADME study also revealed higher drug-likeness scores for compounds than for venetoclax. In conclusion, the tested newly synthesized chalcone-pyridothienopyrimidinone derivatives showed promising antiproliferative and apoptotic effects. Mechanistically, the compounds increased ROS production with concomitant cell cycle arrest and apoptosis. Therefore, regulation of the cell cycle and apoptosis are possible targets for anticancer therapy. The tested compounds could be potent anticancer agents to be tested in future clinical trials after extensive pharmacodynamic, pharmacokinetic, and toxicity profile investigations.
Topics: Apoptosis; Cell Line, Tumor; Chalcones; Hep G2 Cells; Humans; MCF-7 Cells; Molecular Docking Simulation; Molecular Structure; Pyrimidines
PubMed: 35003514
DOI: 10.1155/2021/4759821 -
Chemistry & Biodiversity Dec 2023A library of 6-(((1-(substitutedphenyl)-1H-1,2,3-triazol-4-yl)methyl) amino)-3-methylquinazolin-4(3H)-one analogues synthesized from Isatin precursor through a series of...
A library of 6-(((1-(substitutedphenyl)-1H-1,2,3-triazol-4-yl)methyl) amino)-3-methylquinazolin-4(3H)-one analogues synthesized from Isatin precursor through a series of nitration, reduction, hydrolysis, cyclization and click reaction. The structures of compounds were characterized by spectral data including IR, H-NMR, C NMR and Mass. The novel quinazolinone - 1,2,3-triazoles were screened for their cytotoxicity against the human breast adenocarcinoma cell lines MCF-7 by MTT assay. 4-Isopropyl and 2-bromo substituted analogues executed high activity against MCF-7 cell line with IC value of 10.16±0.07 μM and 11.23±0.20 μM compared to the Doxorubicin whose IC value is 10.81±0.03 μM. The activity of remaining compounds is good to moderate. Further, the molecular docking studies against the crystal structure of Epidermal Growth Factor Receptor delivered the best binding energies and the interactions such as H-bond and hydrophobic are inevitable. The predicted pharmacokinetic properties results showed that these compounds have more drug likeness properties.
Topics: Humans; MCF-7 Cells; Molecular Structure; Structure-Activity Relationship; Triazoles; Quinazolinones; Antineoplastic Agents; Cell Line, Tumor; Molecular Docking Simulation; Cell Proliferation
PubMed: 37708234
DOI: 10.1002/cbdv.202300800 -
Artificial Cells, Nanomedicine, and... Dec 2019The aim of this paper was examining the combined impacts of CuO nanoparticles (CuO NPs), hyperthermia (H), and irradiation (R) on an increment of MCF-7 cells. The MTT...
The aim of this paper was examining the combined impacts of CuO nanoparticles (CuO NPs), hyperthermia (H), and irradiation (R) on an increment of MCF-7 cells. The MTT assay was employed to assess the antiproliferative effects of CuO NPs (25, 50, and 100 μg/ml), hyperthermia (41 °C for 1 h), and irradiation (200 cGy). Moreover, the perniciousness was estimated through the survival capability of cells, and apoptosis, ROS production, and levels of caspase-3, -8 and -9 proteins were determined. A significant (p < .01) decrease in proliferation index (0.124 ± 0.021), a significant (p < .01) increase in apoptosis (42% ± 1.54) of MCF7 cells, a significant (p < .03) increase in ROS formation (32.16 ± 1.9) and a significant (p < .01) increase in LDH release (33.28 ± 1.56) were recorded in the adjacency of MCF-7 cells by a combination of CuO NPs (100 µg/ml) and R + H compared to control and other treatments. The activities of caspase-3 (0.33 ± 0.014) and caspase-9 (0.389 ± 0.019) also increased significantly (p < .05). However, caspase-8 showed no significant changes in its activity (p = .065). Based on these observations, a combination of CuO NPs, hyperthermia, and irradiation could suppress the growth of MCF-7 cells and evoke cell apoptosis via mitochondrial membrane potential.
Topics: Apoptosis; Caspases; Cell Survival; Combined Modality Therapy; Copper; Humans; Hyperthermia, Induced; L-Lactate Dehydrogenase; MCF-7 Cells; Nanoparticles; Radiotherapy; Reactive Oxygen Species
PubMed: 30964344
DOI: 10.1080/21691401.2019.1600529 -
Colombia Medica (Cali, Colombia) Mar 2021Viruses are being used as alternative and complementary tools for treating cancers. Oncolytic viruses exhibit tumor tropism, ability to enhance anti-tumor immunity and...
BACKGROUND
Viruses are being used as alternative and complementary tools for treating cancers. Oncolytic viruses exhibit tumor tropism, ability to enhance anti-tumor immunity and ability to be used in combination with conventional chemotherapy and radiotherapy. We have recently selected some rotavirus isolates which are adapted to efficiently infect and kill tumor cell lines.
AIM
We tested five tumor cell-adapted rotavirus isolates for their ability to infect the human adenocarcinoma cell line MCF-7.
METHODS
Cell surface membrane-associated proteins mediating virus particle attachment were characterized using ELISA, immunoprecipitation, FACS analysis, and antibody blocking.
RESULTS
It was found that heat shock proteins (HSPs) such as Hsp90, Hsp70, Hsp60, and Hsp40 are expressed on the cell surface forming complexes with protein disulfide isomerase (PDI), integrin β3, and heat shock cognate protein 70 (Hsc70) in lipid raft microdomains. Interaction of rotavirus isolates with these cellular proteins was further confirmed by a competition assay and an inhibition assay involving the HSPs tested.
CONCLUSION
Our findings suggest that the tumor cell-adapted rotavirus isolates studied here offer a promising tool for killing tumor cells, thus encouraging further research into this topic, including animal models.
Topics: Adenocarcinoma; HSC70 Heat-Shock Proteins; Heat-Shock Proteins; Humans; MCF-7 Cells; Oncolytic Viruses; Rotavirus
PubMed: 33911319
DOI: 10.25100/cm.v51i4.4196 -
DNA and Cell Biology Aug 2021The interaction of calf thymus DNA (ct DNA) with anastrozole, which is acknowledged as an antineoplastic drug, has been enquired into in the absence and presence of...
Determining the Interaction Behavior of Calf Thymus DNA with Anastrozole in the Presence of Histone H1: Spectroscopies and Cell Viability of MCF-7 Cell Line Investigations.
The interaction of calf thymus DNA (ct DNA) with anastrozole, which is acknowledged as an antineoplastic drug, has been enquired into in the absence and presence of histone H1, through the means of absorbance, fluorescence, circular dichroism spectroscopy, viscosity, thermal melting, and molecular modeling techniques. In addition, the effects of anastrozole on MCF 7 cell line have been thoroughly investigated. Fluorescence spectroscopy results have indicated that quenching mechanism of ct DNA-anastrozole are known as static quenching procedures, since the Stern-Volmer quenching constant (K) seems to face a decrease as the temperature is enhanced; this is a significant evidence for intercalative binding mode of anastrozole with ct DNA. Regarding the ternary system in the presence of H1, the constant of Stern-Volmer quenching was increased as the temperature was heightened. The thermodynamic parameters suggested that the binding could be characterized as exothermic by negative and positive enthalpy and entropy changes in both binary and ternary systems, respectively. It is vital to mention that hydrogen bonds and hydrophobic contributions play significant roles in anastrozole association to ct DNA in the absence and presence of H1. In accordance to the absorption spectroscopy and melting temperature curve outcomes, the binding mode of anastrozole with ct DNA in absence and presence of H1 was indicative of intercalative and nonintercalative bindings, respectively. The viscosity results as binary and ternary systems, which have been elucidated from a sensitive viscometer, have confirmed the fluorescence spectroscopy determinations. The intercalation of anastrozole to ct DNA seemed to be significantly related to an induced reduction in MCF-7 cell proliferation. The molecular modeling results have suggested that anastrozole could bind to H1 in ct DNA-H1 complex in ternary systems, which supports the conclusions that have been obtained from experimental data.
Topics: Anastrozole; Antineoplastic Agents; Cell Proliferation; Cell Survival; DNA; Histones; Humans; Intercalating Agents; MCF-7 Cells; Protein Binding
PubMed: 34165362
DOI: 10.1089/dna.2021.0052 -
Cellular and Molecular Biology... Apr 2022The present study was carried out to investigate anti-tumoral effects of Anandamide (AEA) in luminal A breast cancer cell line MCF-7. Cell viability was measured by MTT...
The present study was carried out to investigate anti-tumoral effects of Anandamide (AEA) in luminal A breast cancer cell line MCF-7. Cell viability was measured by MTT assay and cell index was measured by xCelligence DP analyzer system. The Feulgen method was used to determine the mitotic index parameter, and the 3H-Thymidine method was used to determine the labeling index parameter. The apoptotic index parameter was determined using a fluorescent dye DAPI. The results of this study showed that 25 µM Anandamide concentration was the optimum concentration for MCF-7 cells. While this concentration decreased the proportion of cells in the mitotic phase and synthesis phase, it increased the proportion of apoptotic cells.
Topics: Arachidonic Acids; Breast Neoplasms; Cannabinoids; Endocannabinoids; Female; Humans; MCF-7 Cells; Polyunsaturated Alkamides
PubMed: 35988272
DOI: 10.14715/cmb/2022.68.4.16 -
Molecular Biology Reports Feb 2019Lantana camara is an important medicinal plant that contains many active compounds, including pentacyclic triterpenoids, with numerous biological activities. The present...
Lantana camara is an important medicinal plant that contains many active compounds, including pentacyclic triterpenoids, with numerous biological activities. The present study was conducted to evaluate the anti-oxidant, anti-tumour, and cell cycle arrest properties of chemical compounds extracted from L. camara leaves. Four compounds were identified after subjecting the plant methanolic extract to LC-MS/MS analysis: lantadene A, lantadene B, icterogenin, and lantadene C. Potential antioxidant activity was examined using 2, 2-diphenyl-1-picrylhydrazyl and compared with vitamin C as a control. Lantadene A and B were confirmed to possess the highest scavenging activity, while icterogenin and lantadene C exhibited a lesser antioxidant effect. All extracted compounds exerted a dose-dependent reduction in MCF-7 cell viability; however, lantadene B showed the highest anti-cancer activity, with an IC of 112.2 μg mL, and was therefore used in subsequent experiments. The results also confirmed the significant release of caspase 9 in a dose-dependent pattern following treatment of MCF-7 cells with a range of lantadene B concentrations. Lantadene B was found to induce MCF-7 cell cycle arrest in G1, blocking the G1/S transition with a maximum significant (p ≤ 0.01) cell count of 80.35% at 25 µg mL. No significant changes were observed in S phase, but a decrease in the MCF-7 population was exhibited in G2/M phase.
Topics: Antioxidants; Cell Cycle Checkpoints; Chromatography, Liquid; Humans; Lantana; MCF-7 Cells; Oleanolic Acid; Pentacyclic Triterpenes; Plant Extracts; Plant Leaves; Tandem Mass Spectrometry; Triterpenes
PubMed: 30426385
DOI: 10.1007/s11033-018-4482-3 -
Nutrients Sep 2021Seven derivatives of plant-derived hydroxybenzoic acid (HBA)-including 2,3-dihydroxybenzoic (2,3-DHB, pyrocatechuic), 2,4-dihydroxybenzoic (2,4-DHB, β-resorcylic),...
Plant-Derived and Dietary Hydroxybenzoic Acids-A Comprehensive Study of Structural, Anti-/Pro-Oxidant, Lipophilic, Antimicrobial, and Cytotoxic Activity in MDA-MB-231 and MCF-7 Cell Lines.
Seven derivatives of plant-derived hydroxybenzoic acid (HBA)-including 2,3-dihydroxybenzoic (2,3-DHB, pyrocatechuic), 2,4-dihydroxybenzoic (2,4-DHB, β-resorcylic), 2,5-dihydroxybenzoic (2,5-DHB, gentisic), 2,6-dihydroxybenzoic (2,6-DHB, γ-resorcylic acid), 3,4-dihydroxybenzoic (3,4-DHB, protocatechuic), 3,5-dihydroxybenzoic (3,5-DHB, α-resorcylic), and 3,4,5-trihydroxybenzoic (3,4,5-THB, gallic) acids-were studied for their structural and biological properties. Anti-/pro-oxidant properties were evaluated by using DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS (2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), FRAP (ferric-reducing antioxidant power), CUPRAC (cupric-reducing antioxidant power), and Trolox oxidation assays. Lipophilicity was estimated by means of experimental (HPLC) and theoretical methods. The antimicrobial activity against (), (), (), (), (), and () was studied. The cytotoxicity of HBAs in MCF-7 and MDA-MB-231 cell lines was estimated. Moreover, the structure of HBAs was studied by means of experimental (FTIR, H, and C NMR) and quantum chemical DFT methods (the NBO and CHelpG charges, electrostatic potential maps, and electronic parameters based on the energy of HOMO and LUMO orbitals). The aromaticity of HBA was studied based on the calculated geometric and magnetic aromaticity indices (HOMA, Aj, BAC, I6, NICS). The biological activity of hydroxybenzoic acids was discussed in relation to their geometry, the electronic charge distribution in their molecules, their lipophilicity, and their acidity. Principal component analysis (PCA) was used in the statistical analysis of the obtained data and the discussion of the dependency between the structure and activity (SAR: structure-activity relationship) of HBAs. This work provides valuable information on the potential application of hydroxybenzoic acids as bioactive components in dietary supplements, functional foods, or even drugs.
Topics: Anti-Infective Agents; Antioxidants; Cell Line, Tumor; Cytotoxins; Humans; Hydroxybenzoates; MCF-7 Cells; Plant Extracts; Reactive Oxygen Species; Structure-Activity Relationship
PubMed: 34578985
DOI: 10.3390/nu13093107 -
Nan Fang Yi Ke Da Xue Xue Bao = Journal... Mar 2019To investigate the effects of ribonucleotide reductase catalytic subunit M1 (RRM1) gene silencing on drug resistance of human breast cancer cell line MCF-7/R.
OBJECTIVE
To investigate the effects of ribonucleotide reductase catalytic subunit M1 (RRM1) gene silencing on drug resistance of human breast cancer cell line MCF-7/R.
METHODS
We established a paclitaxel-resistant breast cancer MCF-7 cell line (MCF-7/R) by exposing the cells to high-concentration paclitaxel in a short time. Small interfering RNAs (siRNAs) targeting RRM1 were designed to silence RRM1 expression in human breast cancer MCF-7/R cells. MTT assay was used to detect the IC values and the sensitivity to paclitaxel in the cells with or without siRNA transfection. The changes in the proliferative activity of MCF7 and MCF-7/R cells following RRM1 gene silencing were evaluated using EdU assay. Flow cytometry was used to analyze the cell apoptosis and cell cycle changes. We assessed the effect of RRM1 gene silencing and paclitaxel on the tumor growth in a nude mouse model bearing subcutaneous xenografts with or without siRNA transfection.
RESULTS
We detected significantly higher expressions of RRM1 at both the mRNA and protein levels in the drug-resistant MCF- 7/R cells than in the parental MCF-7 cells ( < 0.01). Transfection with the specific siRNAs significantly reduced the expression of RRM1 in MCF-7/R cells ( < 0.05), which showed a significantly lower IC value of paclitaxel than the cells transfected with the negative control siRNA ( < 0.05). RRM1 silencing significantly inhibited the proliferation ( < 0.01) and enhanced the apoptosis-inducing effect of paclitaxel in MCF-7/R cells ( < 0.001); RRM1 silencing also resulted in obviously reduced Akt phosphorylation, suppressed Bcl-2 expression and promoted the expression of p53 protein in MCF-7/R cells. In the tumor-bearing nude mice, the volume of subcutaneously transplanted tumors was significantly smaller in MCF-7/R/siRNA+ PTX group than in the other groups ( < 0.001).
CONCLUSIONS
RRM1 gene silencing can reverse paclitaxel resistance in human breast cancer cell line MCF-7/R by promoting cell apoptosis.
Topics: Animals; Apoptosis; Breast Neoplasms; Drug Resistance, Neoplasm; Gene Silencing; Humans; MCF-7 Cells; Mice; Mice, Nude; Paclitaxel; RNA, Small Interfering; Ribonucleoside Diphosphate Reductase; Ribonucleotide Reductases; Tumor Suppressor Proteins
PubMed: 31068300
DOI: 10.12122/j.issn.1673-4254.2019.03.08