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The Journal of Organic Chemistry Oct 2022Hydropersulfides (RSSH) have received significant interest in the field of redox biology because of their intriguing biochemical properties. However, because RSSH are...
Hydropersulfides (RSSH) have received significant interest in the field of redox biology because of their intriguing biochemical properties. However, because RSSH are inherently unstable, their study is challenging, and as a result, the details of their physiological roles remain ill-defined. Herein, we report strategies to release RSSH utilizing photoremovable protecting groups. RSSH protection with the well-established -hydroxyphenacyl (HP) photoprotecting group resulted in inefficient RSSH photorelease along with complex chemistry. Therefore, an alternative precursor was examined in which a self-immolative linker was inserted between the HP group and RSSH, providing nearly quantitative RSSH release following photolysis at 365 nm. Inspired by these results, we also synthesized an analogous precursor derivatized with 7-diethylaminocoumarin (DEACM), a visible light-cleavable photoprotecting group. Photolysis of this precursor at 420 nm led to efficient RSSH release, and in vitro experiments demonstrated intracellular RSSH delivery in breast cancer MCF-7 cells.
Topics: Humans; Light; MCF-7 Cells; Oxidation-Reduction; Photolysis
PubMed: 36084133
DOI: 10.1021/acs.joc.2c01049 -
Molecules (Basel, Switzerland) Mar 2022We designed and synthesized the 1,3,4-thiadiazole derivatives differing in the structure of the substituents in C2 and C5 positions. The cytotoxic activity of the...
We designed and synthesized the 1,3,4-thiadiazole derivatives differing in the structure of the substituents in C2 and C5 positions. The cytotoxic activity of the obtained compounds was then determined in biological studies using MCF-7 and MDA-MB-231 breast cancer cells and normal cell line (fibroblasts). The results showed that in both breast cancer cell lines, the strongest anti-proliferative activity was exerted by 2-(2-trifluorometylophenylamino)-5-(3-methoxyphenyl)-1,3,4-thiadiazole. The IC values of this compound against MCF-7 and MDA-MB-231 breast cancer cells were 49.6 µM and 53.4 µM, respectively. Importantly, all new compounds had weaker cytotoxic activity on normal cell line than on breast cancer cell lines. In silico studies demonstrated a possible multitarget mode of action for the synthesized compounds. The most likely mechanism of action for the new compounds is connected with the activities of Caspase 3 and Caspase 8 and activation of BAX proteins.
Topics: Cell Line, Tumor; Cell Proliferation; Humans; MCF-7 Cells; Thiadiazoles
PubMed: 35335177
DOI: 10.3390/molecules27061814 -
Macromolecular Bioscience Jul 2021Here, as a proof of concept, hybrid vesicles (VEs) are developed from two types of cancer cells, MCF-7 and HeLa, for the dual targeting of the anticancer drug...
Here, as a proof of concept, hybrid vesicles (VEs) are developed from two types of cancer cells, MCF-7 and HeLa, for the dual targeting of the anticancer drug doxorubicin (Dox) to cancer cells via homotypic interactions. Hybrid VEs with a size of 181.8 ± 28.2 nm and surface charge of -27.8 ± 1.9 mV are successfully prepared by the fusion of MCF-7 and HeLa VEs, as demonstrated by the fluorescence resonance energy transfer assay. The hybrid VEs exhibit enhanced intracellular uptake both in MCF-7 and HeLa cells. Dox-encapsulated hybrid VEs (Dox-hybrid VEs) also exhibit promising anticancer and antiproliferative activities against MCF-7/multidrug-resistant cells and HeLa cells. In addition, compared to free Dox, the Dox-hybrid VEs exhibit low intracellular uptake and reduced cytotoxicity for RAW264.7 cells. Thus, hybrid VEs with dual-targeting activity toward two types of cancer cells may be useful for the specific targeting of anticancer drugs for improved anticancer effects with reduced nonspecific toxicity.
Topics: Antineoplastic Agents; Doxorubicin; Drug Resistance, Neoplasm; HeLa Cells; Humans; MCF-7 Cells; Neoplasms
PubMed: 33963822
DOI: 10.1002/mabi.202100067 -
Anticancer Research Mar 2023An increasing number of studies are reporting anticancer activity of widely used antiparasitic drugs and particularly benzimidazoles. Fenbendazole is considered safe and...
BACKGROUND/AIM
An increasing number of studies are reporting anticancer activity of widely used antiparasitic drugs and particularly benzimidazoles. Fenbendazole is considered safe and tolerable in most animal species at the effective doses as an anthelmintic. Little is known about the redox-modulating properties of fenbendazole and the molecular mechanisms of its antiproliferative effects. Our study aimed to investigate the possibility of selective redox-mediated treatment of triple-negative breast cancer cells by fenbendazole without affecting the viability and redox status of normal breast epithelial cells.
MATERIALS AND METHODS
The experiments were performed on three cell lines: normal breast epithelial cells (MCF-10A) and cancer breast epithelial cells (MCF7 - luminal adenocarcinoma, low metastatic; MDA-MB-231 - triple-negative adenocarcinoma, highly metastatic). Cells were treated with fenbendazole for 48-h and three parameters were analyzed using conventional assays: cell viability and proliferation, level of intracellular superoxide, and level of hydroperoxides.
RESULTS
The data demonstrated that MDA-MB-231 cells were more vulnerable to fenbendazole-induced oxidative stress than MCF-7 cells. In normal breast epithelial cells MCF-10A, fenbendazole significantly suppressed oxidative stress compared to untreated controls. These data correlate with the effect of fenbendazole on cell viability and the IC values, which is indirect evidence of the potential targeting anticancer effect of the drug, especially in MDA-MB-231 cells.
CONCLUSION
The difference in the levels of oxidative stress induced by fenbendazole in MDA-MB-231 and MCF-7 indicates that the two types of breast cancer respond to the drug through different redox-related mechanisms.
Topics: Animals; Humans; Triple Negative Breast Neoplasms; Fenbendazole; Epithelial Cells; Adenocarcinoma; MCF-7 Cells
PubMed: 36854536
DOI: 10.21873/anticanres.16267 -
BMB Reports Mar 2022Etoposide is a chemotherapeutic medication used to treat various types of cancer, including breast cancer. It is established that pulsed electromagnetic field (PEMF)...
Etoposide is a chemotherapeutic medication used to treat various types of cancer, including breast cancer. It is established that pulsed electromagnetic field (PEMF) therapy can enhance the effects of anti-cancer chemotherapeutic agents. In this study, we investigated whether PEMFs influence the anti-cancer effects of etoposide in MCF-7 cells and determined the signal pathways affected by PEMFs. We observed that co-treatment with etoposide and PEMFs led to a decrease in viable cells compared with cells solely treated with etoposide. PEMFs elevated the etoposide- induced PARP cleavage and caspase-7/9 activation and enhanced the etoposide-induced down-regulation of survivin and up-regulation of Bax. PEMF also increased the etoposideinduced activation of DNA damage-related molecules. In addition, the reactive oxygen species (ROS) level was slightly elevated during etoposide treatment and significantly increased during co-treatment with etoposide and PEMF. Moreover, treatment with ROS scavenger restored the PEMF-induced decrease in cell viability in etoposide-treated MCF-7 cells. These results combined indicate that PEMFs enhance etoposide-induced cell death by increasing ROS induction-DNA damage-caspase-dependent apoptosis. [BMB Reports 2022; 55(3): 148-153].
Topics: Apoptosis; Electromagnetic Fields; Etoposide; Humans; MCF-7 Cells; Reactive Oxygen Species
PubMed: 34674796
DOI: 10.5483/BMBRep.2022.55.3.119 -
(Pro)renin receptor and insulin signalling regulate cell proliferation in MCF-7 breast cancer cells.Journal of Biochemistry Dec 2022(Pro)renin receptor [(P)RR] is related to both the renin-angiotensin system and V-ATPase with various functions including stimulation of cell proliferation. (P)RR is...
(Pro)renin receptor [(P)RR] is related to both the renin-angiotensin system and V-ATPase with various functions including stimulation of cell proliferation. (P)RR is implicated in the pathophysiology of diabetes mellitus and cancer. Hyperinsulinemia is observed in obesity-related breast cancer. However, the relationship between (P)RR and insulin has not been clarified. We have therefore studied the effect of insulin on (P)RR expression, cell viability and AKT phosphorylation under the conditions with and without (P)RR knockdown. Effects of insulin were studied in a human breast cancer cell line, MCF-7. Cell proliferation assay was performed by WST-8 assay. (P)RR expression was suppressed by (P)RR-specific siRNAs. The treated cells were analysed by western blotting and reverse transcriptase-quantitative polymerase chain reaction analysis. Insulin stimulated proliferation of MCF-7 cells and increased (P)RR protein expression, but not (P)RR mRNA levels. Moreover, autophagy flux was suppressed by insulin. Suppression of (P)RR expression reduced cell number of MCF-7 cells and AKT phosphorylation significantly in both the presence and the absence of insulin, indicating that (P)RR is important for cell viability and AKT phosphorylation. In conclusion, insulin upregulates the level of (P)RR protein, which is important for cell viability, proliferation, AKT phosphorylation and autophagy in breast cancer cells.
Topics: Humans; Breast Neoplasms; Cell Proliferation; Insulin; MCF-7 Cells; Phosphorylation; Proto-Oncogene Proteins c-akt; Prorenin Receptor
PubMed: 36071571
DOI: 10.1093/jb/mvac072 -
Biological & Pharmaceutical Bulletin 2022Solid tumors habitually harbor regions with insufficient oxygen away from vasculature. Hypoxia is an important factor that confers malignant phenotypes like...
Solid tumors habitually harbor regions with insufficient oxygen away from vasculature. Hypoxia is an important factor that confers malignant phenotypes like chemoresistance to tumor cells. We have demonstrated that cathepsin G (CG) stimulates cell aggregation in breast cancer MCF-7 cells by activating insulin-like growth factor-1 signaling. We investigated whether cancer cell aggregates induced by CG acquire hypoxia-dependent chemoresistance. Pimonidazole staining and hypoxia-inducible factor (HIF)-1α and -2α expression indicated that the core of the cell aggregates was hypoxic. Electrophoretic mobility shift and reporter assays showed that the CG-induced cell aggregates displayed transcriptional activity through HIF-responsive elements. Moreover, HIF target genes PGK1 and SLC2A1 demonstrated upregulated expression in CG-induced cell aggregates, indicating that the aggregates expressed functional HIF. Doxorubicin (DXR)-induced cytotoxicity was significantly lower in the cell aggregates induced by CG compared with monolayer cells under normoxia. Unexpectedly, the upregulation of P-glycoprotein expression, which is reported to be a HIF-target gene, and decreasing intracellular accumulation of DXR was not detected in the cell aggregates as opposed to in monolayer cells under normoxia. Additionally, reduction of DXR sensitivity in the aggregates was not suppressed by treatment with the HIF inhibitor, YC-1 and HIF-1α small interfering RNA (siRNA). Therefore, we conclude that cell aggregation induced by CG decreases DXR sensitivity via a HIF-independent mechanism.
Topics: Humans; Cathepsin G; MCF-7 Cells; Doxorubicin; Cell Aggregation; RNA, Small Interfering; Hypoxia; Neoplasms
PubMed: 36450530
DOI: 10.1248/bpb.b22-00447 -
Journal of Cosmetic Dermatology Jan 2020UV filters should be determined a strict toxicological safety prior to approval. Homosalate (HMS) is one of the most widely used organic UV filter. HMS accumulates in...
BACKGROUND
UV filters should be determined a strict toxicological safety prior to approval. Homosalate (HMS) is one of the most widely used organic UV filter. HMS accumulates in aquatic biota ecosystems and humans through the food chain; therefore, it is important to consider the effects on health and know its mechanisms of action.
AIMS
The study aimed to evaluate the cytotoxic and genotoxic effects of HMS in MCF-7 cell line.
METHODS
Cell viability was examined by the 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) and cell membrane integrity by the lactate dehydrogenase release assays (LDH), and genotoxicity by using the micronucleus test at 250, 500, 750, 1000, 1500, and 2000 µM concentrations with the human breast cell line MCF-7.
RESULTS
Homosalate affected the cell viability dose-dependently at a concentrations of above 1000 µM. Micronucleus formation was significantly induced at 750 and 1000 µM within 24 hours due to an increase in cytostatic effect, the cell viability of HMS decreased to 57% at a concentration of 2000 µM, and a sufficient number of binucleated cells could not be obtained to count. Homosalate was also clastogenic when the cells were incubated at cytotoxic concentrations.
CONCLUSION
These results suggest that homosalate can be considered as a cytotoxic and genotoxic substance.
Topics: Apoptosis; Cell Survival; DNA Damage; Dose-Response Relationship, Drug; Humans; MCF-7 Cells; Micronucleus Tests; Salicylates; Sunscreening Agents; Toxicity Tests, Acute
PubMed: 31021040
DOI: 10.1111/jocd.12973 -
Integrative Cancer Therapies 2021In this study, the potential of an n-butanol fraction from to prevent metastasis in MCF-7 breast cancer cells was investigated. The effect of the fraction on BUD-8 and...
In this study, the potential of an n-butanol fraction from to prevent metastasis in MCF-7 breast cancer cells was investigated. The effect of the fraction on BUD-8 and MCF-7 cell viability was assessed using the MTT assay. Apoptotic cell death was analyzed by Hoechst staining assay. The antimetastatic effect of the fraction on MCF-7 cell was evaluated using the wound healing, adhesion and Boyden chamber invasion assays. Gelatin-zymography was used to assess the effect of the fraction on MMP-2 and MMP-9 activity. The expression profile of proteins implicated in metastasis and angiogenesis was determined using the human angiogenesis antibody array kit, following treatment with the fraction. BUD-8 cell viability was significantly reduced at concentrations between 300 and 500 µg/ml of the extract. In contrast, a significant reduction in cell viability was seen in MCF-7 cells treated with 400 to 500 µg/ml of the fraction. At sub-lethal concentrations (100 and 200 µg/ml) of the fraction, no nuclei morphological changes associated with apoptotic cell death were observed in MCF-7 cells. In addition, the fraction showed to have an inhibitory effect on MCF-7 cell migration, adhesion, invasiveness, and MMP-2 activity. Moreover, the fraction was seen to modulate the expression of several proteins, such as MMP-9, uPA, VEGF, and TGF-β1, playing a role in the metastasis process. This study demonstrates that the -butanol fraction of can inhibit major steps of the metastatic cascade and modulate metastasis regulatory proteins. Thus, the fraction can be considered a potential source of antimetastatic agents that could be useful in the treatment of malignant cancers.
Topics: 1-Butanol; Breast Neoplasms; Butanols; Cell Adhesion; Cell Line, Tumor; Cell Movement; Female; Gene Expression Regulation, Neoplastic; Humans; MCF-7 Cells; Neoplasm Invasiveness; Ricinus
PubMed: 33565349
DOI: 10.1177/1534735420977684 -
Chemistry & Biodiversity Jan 2023Breast cancer is known as the most common type of invasive cancer in women. It is well-known that phenolic compounds play an important role in the treatment of this...
Breast cancer is known as the most common type of invasive cancer in women. It is well-known that phenolic compounds play an important role in the treatment of this disease. This study hypothesized that isoeugenol based two polyphenolic compounds 1 and 2 exerts its anti-proliferative effects through the induction of apoptosis and cell migration arrest on human breast cancer cell. Based on this hypothesis, the study aimed to investigate the anti-proliferative, anti-migrative effects of these compounds and their possible basic molecular mechanisms of action in MCF-7 cell lines. As a result, isoeugenol-based compounds 1 and 2 showed anti-proliferative, anti-apoptotic and anti-migrative effects in MCF-7 breast cancer cells. This result was supported by molecular analyzes and it was determined that there were changes in the expression of some gene regions involved in apoptosis and migration. Additionally, it was a remarkable result that cell viability inhibition did not occur in healthy breast tissue cells and no cytotoxic effect was observed. The existence of such a differentiation between cancer cells and healthy cells significantly increases the potential of these compounds to be used as chemotherapeutic drug active ingredients without side effects.
Topics: Humans; Female; MCF-7 Cells; Breast Neoplasms; Cell Proliferation; Polyphenols; Early Detection of Cancer; Antineoplastic Agents; Apoptosis; Cell Line, Tumor
PubMed: 36594615
DOI: 10.1002/cbdv.202200872