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Molecules (Basel, Switzerland) Jun 2024A series of phenyl -carbonyl selenides with o-ester functionality substituted on the oxygen atom with chiral and achiral alkyl groups was synthesized. All compounds are...
A series of phenyl -carbonyl selenides with o-ester functionality substituted on the oxygen atom with chiral and achiral alkyl groups was synthesized. All compounds are the first examples of this type of organoselenium derivatives with an ester substituent in the ortho position. The obtained derivatives were tested as antioxidants and anticancer agents to see the influence of an ester functionality on the bioactivity of -carbonyl selenides by replacing the -amide group with an -ester group. The best results as an antioxidant agent were observed for -((1,2,5)-(-)-2-isopropyl-5-methylcyclohexyl)-2-((2-oxopropyl)selanyl)benzoate. The most cytotoxic derivative against breast cancer MCF-7 cell lines was -(methyl)-2-((2-oxopropyl)selanyl)benzoate and against human promyelocytic leukemia HL-60 was -(2-pentyl)-2-((2-oxopropyl)selanyl)benzoate.
Topics: Humans; Antineoplastic Agents; Antioxidants; Esters; Organoselenium Compounds; MCF-7 Cells; HL-60 Cells; Structure-Activity Relationship; Molecular Structure
PubMed: 38930931
DOI: 10.3390/molecules29122866 -
Molecules (Basel, Switzerland) Jun 2024Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a crucial tumor suppressor protein with frequent mutations and alterations. Although protein...
Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a crucial tumor suppressor protein with frequent mutations and alterations. Although protein therapeutics are already integral to numerous medical fields, their potential remains nascent. This study aimed to investigate the impact of stable, unphosphorylated recombinant human full-length PTEN and its truncated variants, regarding their tumor suppression activity with multiwalled-carbon nanotubes (MW-CNTs) as vehicles for their delivery in breast cancer cells (T-47D, ZR-75-1, and MCF-7). The cloning, overexpression, and purification of PTEN variants were achieved from , followed by successful binding to CNTs. Cell incubation with protein-functionalized CNTs revealed that the full-length PTEN-CNTs significantly inhibited cancer cell growth and stimulated apoptosis in ZR-75-1 and MCF-7 cells, while truncated PTEN fragments on CNTs had a lesser effect. The N-terminal fragment, despite possessing the active site, did not have the same effect as the full length PTEN, emphasizing the necessity of interaction with the C2 domain in the C-terminal tail. Our findings highlight the efficacy of full-length PTEN in inhibiting cancer growth and inducing apoptosis through the alteration of the expression levels of key apoptotic markers. In addition, the utilization of carbon nanotubes as a potent PTEN protein delivery system provides valuable insights for future applications in in vivo models and clinical studies.
Topics: PTEN Phosphohydrolase; Nanotubes, Carbon; Humans; Breast Neoplasms; Female; Apoptosis; Cell Line, Tumor; Cell Proliferation; MCF-7 Cells; Antineoplastic Agents
PubMed: 38930850
DOI: 10.3390/molecules29122785 -
Molecules (Basel, Switzerland) Jun 2024The current article reports the investigation of three new Ni(II) complexes with -donor dithiocarbazate ligands: [Ni(L)PPh] (), [Ni(L)PPh] (), and [Ni(L)Py] ()....
The current article reports the investigation of three new Ni(II) complexes with -donor dithiocarbazate ligands: [Ni(L)PPh] (), [Ni(L)PPh] (), and [Ni(L)Py] (). Single-crystal X-ray analyses revealed mononuclear complexes with a distorted square planar geometry and the metal centers coordinated with a doubly deprotonated dithiocarbazate ligand and coligand pyridine or triphenylphosphine. The non-covalent interactions were investigated by the Hirshfeld surface and the results revealed that the strongest interactions were π⋅⋅⋅π stacking interactions and non-classical hydrogen bonds C-H···H and C-H···N. Physicochemical and spectroscopic methods indicate the same structures in the solid state and solution. The toxicity effects of the free ligands and Ni(II) complexes were tested on the human breast cancer cell line MCF-7 and non-malignant breast epithelial cell line MCF-10A. The half-maximal inhibitory concentration (IC) values, indicating that the compounds were potent in inhibiting cell growth, were obtained for both cell lines at three distinct time points. While inhibitory effects were evident in both malignant and non-malignant cells, all three complexes demonstrated lower IC values for malignant breast cell lines than their non-malignant counterparts, suggesting a stronger impact on cancerous cell lines. Furthermore, molecular docking studies were performed showing the complex () as a promising candidate for further therapeutic exploration.
Topics: Humans; Nickel; Molecular Docking Simulation; Antineoplastic Agents; Ligands; Coordination Complexes; Cell Line, Tumor; Crystallography, X-Ray; MCF-7 Cells; Molecular Structure; Cell Proliferation; Drug Design
PubMed: 38930825
DOI: 10.3390/molecules29122759 -
Antioxidants (Basel, Switzerland) Jun 2024, commonly recognized as goji berry or wolfberry, is highly appreciated not only for its organoleptic and nutritional properties but also as an important source of...
, commonly recognized as goji berry or wolfberry, is highly appreciated not only for its organoleptic and nutritional properties but also as an important source of bioactive compounds such as polysaccharides, carotenoids, phenolics, and various other non-nutritive compounds. These constituents give it a multitude of health benefits, including antioxidant, anti-inflammatory, and anticancer properties. However, the precise biochemical mechanisms responsible for its anticancer effects remain unclear, and the comprehensive composition of goji berry extracts is often insufficiently explored. This study aimed to investigate the biochemical pathways modulated in breast cancer cells by an ethanolic extract of fruit (LBE). Following metabolomic profiling using UHPLC-HRMS/MS, we assessed the antitumoral properties of LBE on different breast cancer cell lines. This investigation revealed that LBE exhibited cytotoxic effects, inducing a pro-oxidant effect that triggered pyroptosis activation through endoplasmic reticulum (ER) stress and subsequent activation of the P-IRE1α/XBP1/NLRP3 axis in MCF-7 cells. In addition, LBE did not display cytotoxicity toward healthy human cells but demonstrated antioxidant properties by neutralizing ROS generated by doxorubicin. These findings underscore the potential of LBE as a highly promising natural extract in cancer therapy.
PubMed: 38929147
DOI: 10.3390/antiox13060708 -
Antioxidants (Basel, Switzerland) May 2024Breast cancer presents a significant global health challenge with rising incidence rates worldwide. Despite current efforts, it remains inadequately controlled....
Mechanism of Action of Isoflavone Derived from Soy-Based Tempeh as an Antioxidant and Breast Cancer Inhibitor via Potential Upregulation of miR-7-5p: A Multimodal Analysis Integrating Pharmacoinformatics and Cellular Studies.
Breast cancer presents a significant global health challenge with rising incidence rates worldwide. Despite current efforts, it remains inadequately controlled. Functional foods, notably tempeh, have emerged as promising candidates for breast cancer prevention and treatment due to bioactive peptides and isoflavones exhibiting potential anticancer properties by serving as antioxidants, inducing apoptosis, and inhibiting cancer cell proliferation. This study integrates pharmacoinformatics and cellular investigations (i.e., a multifaceted approach) to elucidate the antioxidative and anti-breast cancer properties of tempeh-derived isoflavones. Methodologies encompass metabolomic profiling, in silico analysis, antioxidant assays, and in vitro experiments. Daidzein and genistein exhibited potential therapeutic options for breast cancer treatment and as antioxidant agents. In vitro studies also supported their efficacy against breast cancer and their ability to scavenge radicals, particularly in soy-based tempeh powder (SBT-P) and its isoflavone derivatives. Results have demonstrated a significant downregulation of breast cancer signaling proteins and increased expression of miR-7-5p, a microRNA with tumor-suppressive properties. Notably, the LD values of SBT-P and its derivatives on normal breast cell lines indicate their potential safety, with minimal cytotoxic effects on MCF-10A cells compared to control groups. The study underscores the favorable potential of SBT-P as a safe therapeutic option for breast cancer treatment, warranting further clinical exploration.
PubMed: 38929071
DOI: 10.3390/antiox13060632 -
Cytoprotective Role of Autophagy in CDIP1 Expression-Induced Apoptosis in MCF-7 Breast Cancer Cells.International Journal of Molecular... Jun 2024Cell death-inducing p53-target protein 1 (CDIP1) is a proapoptotic protein that is normally expressed at low levels and is upregulated by genotoxic and endoplasmic...
Cell death-inducing p53-target protein 1 (CDIP1) is a proapoptotic protein that is normally expressed at low levels and is upregulated by genotoxic and endoplasmic reticulum stresses. CDIP1 has been reported to be localized to endosomes and to interact with several proteins, including B-cell receptor-associated protein 31 (BAP31) and apoptosis-linked gene 2 (ALG-2). However, the cellular and molecular mechanisms underlying CDIP1 expression-induced apoptosis remain unclear. In this study, we first demonstrated that CDIP1 was upregulated after treatment with the anticancer drug adriamycin in human breast cancer MCF-7 cells but was degraded rapidly in the lysosomal pathway. We also demonstrated that treatment with the cyclin-dependent kinase 5 (CDK5) inhibitor roscovitine led to an increase in the electrophoretic mobility of CDIP1. In addition, a phosphomimetic mutation at Ser-32 in CDIP1 resulted in an increase in CDIP1 expression-induced apoptosis. We also found that CDIP1 expression led to the induction of autophagy prior to apoptosis. Treatment of cells expressing CDIP1 with SAR405, an inhibitor of the class III phosphatidylinositol 3-kinase VPS34, caused a reduction in autophagy and promoted apoptosis. Therefore, autophagy is thought to be a defense mechanism against CDIP1 expression-induced apoptosis.
Topics: Humans; Autophagy; Apoptosis; MCF-7 Cells; Breast Neoplasms; Female; Apoptosis Regulatory Proteins; Doxorubicin; Gene Expression Regulation, Neoplastic; Class III Phosphatidylinositol 3-Kinases; Cytoprotection
PubMed: 38928226
DOI: 10.3390/ijms25126520 -
International Journal of Molecular... Jun 2024Breast cancer stands as one of the foremost cause of cancer-related deaths globally, characterized by its varied molecular subtypes. Each subtype requires a distinct...
Breast cancer stands as one of the foremost cause of cancer-related deaths globally, characterized by its varied molecular subtypes. Each subtype requires a distinct therapeutic strategy. Although advancements in treatment have enhanced patient outcomes, significant hurdles remain, including treatment toxicity and restricted effectiveness. Here, we explore the anticancer potential of novel 1,4-naphthoquinone/4-quinolone hybrids on breast cancer cell lines. The synthesized compounds demonstrated selective cytotoxicity against Luminal and triple-negative breast cancer (TNBC) cells, which represent the two main molecular types of breast cancer that depend most on cytotoxic chemotherapy, with potency comparable to doxorubicin, a standard chemotherapeutic widely used in breast cancer treatment. Notably, these derivatives exhibited superior selectivity indices (SI) when compared to doxorubicin, indicating lower toxicity towards non-tumor MCF10A cells. Compounds 11a and 11b displayed an improvement in IC values when compared to their precursor, 1,4-naphthoquinone, for both MCF-7 and MDA-MB-231 and a comparable value to doxorubicin for MCF-7 cells. Also, their SI values were superior to those seen for the two reference compounds for both cell lines tested. Mechanistic studies revealed the ability of the compounds to induce apoptosis and inhibit clonogenic potential. Additionally, the irreversibility of their effects on cell viability underscores their promising therapeutic utility. In 3D-cell culture models, the compounds induced morphological changes indicative of reduced viability, supporting their efficacy in a more physiologically relevant model of study. The pharmacokinetics of the synthesized compounds were predicted using the SwissADME webserver, indicating that these compounds exhibit favorable drug-likeness properties and potential as antitumor agents. Overall, our findings underscore the promise of these hybrid compounds as potential candidates for breast cancer chemotherapy, emphasizing their selectivity and efficacy.
Topics: Humans; Naphthoquinones; Antineoplastic Agents; Female; Breast Neoplasms; Cell Line, Tumor; MCF-7 Cells; Quinolones; Apoptosis; Cell Culture Techniques, Three Dimensional; Doxorubicin; Cell Proliferation; Cell Survival
PubMed: 38928197
DOI: 10.3390/ijms25126490 -
Biomolecules Jun 2024Amino acid deprivation therapy (AADT) is a novel anticancer therapy, considered nontoxic and selective. Thermophilic L-asparaginase enzymes display high stability and...
Amino acid deprivation therapy (AADT) is a novel anticancer therapy, considered nontoxic and selective. Thermophilic L-asparaginase enzymes display high stability and activity at elevated temperatures. However, they are of limited use in clinical applications because of their low substrate affinity and reduced activity under physiological conditions, which may necessitate an improved dosage, leading to side effects and greater costs. Thus, in an attempt to improve the activity of L-Asn at 37 °C, with the use of a semi-rational design, eight active-site mutants of DSM 5473 L-asparaginase Tli10209 were developed. T70A exhibited a 5.11-fold increase compared with the wild enzyme in physiological conditions. Double-mutant enzymes were created by combining mutants with higher hydrolysis activity. T70A/F36Y, T70A/K48L, and T70A/D50G were enhanced by 5.59-, 6.38-, and 5.58-fold. The immobilized enzyme applied in MCF-7 breast cancer cells only required one-seventh of the dose of the free enzyme to achieve the same inhibition rate under near-infrared irradiation. This provides a proof of concept that it is possible to reduce the consumption of L-Asn by improving its activity, thus providing a method to manage side effects.
Topics: Asparaginase; Humans; Antineoplastic Agents; Mutagenesis, Site-Directed; MCF-7 Cells; Thermococcus; Catalytic Domain
PubMed: 38927089
DOI: 10.3390/biom14060686 -
Environmental Science and Pollution... Jun 2024The present work was designed to synthesize AgO-supported MgO/rGO nanocomposites (NCs) via green method using Phoenix leaf extract for improved photocatalytic and...
Green hydrothermal synthesis and characterization of AgO-supported MgO/rGO nanocomposites by using Phoenix leaf extract: a promising approach for enhanced photocatalytic and anticancer activities.
The present work was designed to synthesize AgO-supported MgO/rGO nanocomposites (NCs) via green method using Phoenix leaf extract for improved photocatalytic and anticancer activity. Green synthesized AgO-supported MgO/rGO NCs were characterized through X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), X-ray photoelectron spectroscopy (XPS), Raman, ultraviolet-visible (UV-vis) spectroscopy, and photoluminescence (PL) spectroscopy, and gas chromatography-mass spectroscopy (GC-MS) was applied to examine the chemical components of the Phoenix leaf extract. Characterization data confirmed the preparation of MgO NPs, AgO-MgO NCs, and AgO-MgO/rGO NC with particle size of 26-28 nm. UV-vis study exhibited that the band gap energy of MgO NPs, AgO-MgO NCs, and AgO-MgO/rGO NC were in the range of 3.53-3.43 eV. The photocatalytic results showed that the photodegradation of Rh B dye of AgO-supported MgO/rGO NCs (82.81%) was significantly higher than pure MgO NPs. Additionally, the biological response demonstrates that the AgO-supported MgO/rGO NCs induced high cytotoxicity against MCF-7 cancer cells for 24 h and 48 h compared with both pure MgO NPs and AgO-MgO NCs. This study suggests that the adding of AgO and rGO sheets played significant role in the enhanced photocatalytic and anticancer performance of MgO NPs.
PubMed: 38926309
DOI: 10.1007/s11356-024-33998-0 -
Anticancer Research Jul 2024Clinical diagnostic value of circ-ARHGER28 in breast cancer (BC), and the biological functions of circ-ARHGER28 on the proliferation and apoptosis of MCF-7 cells were...
BACKGROUND/AIM
Clinical diagnostic value of circ-ARHGER28 in breast cancer (BC), and the biological functions of circ-ARHGER28 on the proliferation and apoptosis of MCF-7 cells were investigated.
MATERIALS AND METHODS
Human circRNA microarray was performed to analyze the expression of circRNAs in BC patients. RT-qPCR combined with bioinformatics analysis was applied to verify the candidate circRNAs in BC tissues and peripheral blood samples. Circ-ARHGER28 was chosen as the candidate gene for further research. The clinical diagnostic value and biological functions of circ-ARHGER28 were analyzed. The overexpression and negative control vector of circ-ARHGER28 were constructed and transfected to MCF-7 cells. The CCK 8 assay and clone formation experiments were applied to detect the cell proliferative and migratory abilities. Flow cytometry was used to analyze cell apoptosis and cell cycle distribution. RT-qPCR and Western blot were performed to detect apoptosis and expression of PI3K/AKT/mTOR-associated genes and proteins.
RESULTS
Overexpression of circ-ARHGER28 inhibited the proliferation, colony formation and migration of MCF-7 cells, while increasing the population of the cells in the G/M phase and the apoptotic rate. Apoptosis associated genes and proteins were significantly increased, whereas gene and protein expression of PI3K, AKT and mTOR were decreased in the cells.
CONCLUSION
Circular RNA ARHGER28 exhibits promising diagnostic value for BC. Circ-ARHGER28 inhibited MCF-7 cell proliferation and increased the apoptotic rate. The function of circ-ARHGER28 was associated with the PI3K/AKT/mTOR signaling pathway. Circ-ARHGER28 could be an ideal biomarker for BC diagnosis and a novel target for BC therapy.
Topics: Humans; Breast Neoplasms; Cell Proliferation; Female; Apoptosis; RNA, Circular; MCF-7 Cells; Proto-Oncogene Proteins c-akt; Gene Expression Regulation, Neoplastic; TOR Serine-Threonine Kinases; Biomarkers, Tumor; Signal Transduction; Phosphatidylinositol 3-Kinases; Cell Movement; Middle Aged
PubMed: 38925846
DOI: 10.21873/anticanres.17100