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Biochemistry Research International 2024The plant has been utilized in folk medicine. Analyzing phytochemical composition of dichloromethane/methanol (1 : 1) root part of gave oleic acid (), caffeic...
The plant has been utilized in folk medicine. Analyzing phytochemical composition of dichloromethane/methanol (1 : 1) root part of gave oleic acid (), caffeic acid-2-hydroxynonylester (), catechin (), and a pregnane derivative (). NMR spectroscopy was used to characterize compounds , while compound was identified through GC-MS analysis and literature comparison. The cytotoxicity of extracts from roots of was conducted against MCF-7 cell lines (human breast cancer) by MTT assay. According to the cytotoxicity study, -hexane extract exhibited a high level of toxicity with 28.9 ± 5.6% cell viability. Antibacterial activity was tested against , , , and The highest bacterial growth mean inhibition zone was measured for catechin (3) (13.72 ± 0.05 mm)) against at 0.25 mg/mL and acceptable related to standard. Antioxidant activity was studied by the DPPH assay. Based on the data from the antioxidant study, DCM/MeOH extract (70.32%) and catechin () showed good antioxidant activity (65.61%) (IC 0.25 g/mL) relative to that of the positive control (78.21%, IC 0.014 g/mL) at 12.5 g/mL. In each docking pose, catechin () scored higher binding affinity of -7.9, -7.2, and -6.4 kcal/mol towards PqsA, DNA gyraseB, and PK, respectively, compared to amoxicillin (-8.1, -6.1, and -6.4 kcal/mol). All five Lipinski rules were obeyed by compounds , which showed an acceptable drug resemblance. The lipophilicity was computed as less than five (1.47-4.01) indicating a lipophilic property. Catechin () obeys Veber's rule implying its good oral bioavailability. Binding affinity scores of catechin ()-protein interactions are in line with those from tests, indicating its potential antibacterial effect. The obtained cytotoxicity and antibacterial activity results support the utilization of in folk medicine.
PubMed: 38948887
DOI: 10.1155/2024/3713620 -
OncoTargets and Therapy 2024The increasing incidence of cancer diseases necessitates the urgent exploration of new bioactive compounds. One of the trends in drug discovery is marine sponges which...
INTRODUCTION
The increasing incidence of cancer diseases necessitates the urgent exploration of new bioactive compounds. One of the trends in drug discovery is marine sponges which is gaining significant support due to the abundant production of natural pharmaceutical compounds obtained from marine ecosystems. This study evaluates the anticancer properties of an organic extract from the Red Sea sponge on HepG-2 and MCF-7 cancer cell lines.
METHODS
was collected, freeze-dried, and extracted using a methanol-dichloromethane mixture. The extract was analyzed via Liquid Chromatography-Mass Spectrometry. Cytotoxic effects were assessed through cell viability assays, apoptosis detection, cell cycle analysis, mitochondrial membrane potential assays, scratch-wound healing assays, and 3D cell culture assays.
RESULTS
Fifteen compounds were identified in the extract. The extract showed moderate cytotoxicity against MCF-7 and HepG-2 cells, with IC values of 35.6 ± 6.9 μg/mL and 64.4 ± 8 μg/mL, respectively, after 48 hours of treatment. It induced cell cycle arrest at the G2/M phase in MCF-7 cells and the S phase in HepG-2 cells. Apoptosis increased significantly in both cell lines, accompanied by reduced mitochondrial membrane potential. The extract inhibited cell migration, with notable reductions after 24 and 48 hours. In 3D cell cultures, the extract had IC values of 5.1 ± 2 μg/mL for MCF-7 and 166.4 ± 27 μg/mL for HepG-2 after 7 days of treatment, showing greater potency in MCF-7 spheres compared to HepG-2 spheres.
DISCUSSION AND CONCLUSION
The anticancer activity is attributed to the bioactive compounds. The extract's ability to induce apoptosis, disrupt mitochondrial membrane potential, and arrest the cell cycle highlights its potential as a novel anticancer agent. Additional research is required to investigate the underlying mechanism by which this extract functions as a highly effective anticancer agent.
PubMed: 38948385
DOI: 10.2147/OTT.S467083 -
Britannin suppresses MCF-7 breast cancer cell growth by inducing apoptosis and inhibiting autophagy.Avicenna Journal of Phytomedicine 2024Breast cancer is the main reason for cancer-related death in women. Britannin is a sesquiterpene lactone compound derived from with anti-tumor properties. We aimed to...
OBJECTIVE
Breast cancer is the main reason for cancer-related death in women. Britannin is a sesquiterpene lactone compound derived from with anti-tumor properties. We aimed to explore the impacts of britannin on apoptosis and autophagy in MCF-7 breast cancer cell line.
MATERIALS AND METHODS
The cytotoxic influences of britannin on MCF-7 cells were estimated by the MTT method. The expression levels of apoptosis-associated genes such as , , , , and and transcripts of autophagy markers including , , , , , , and were quantified using quantitative real time-PCR (qRT-PCR). Western blotting method was used to evaluate the amount of caspase 3, phosphorylated JAK2, phosphorylated STAT3, ATG1, ATG4, ATG5, Beclin1, and LC-III.
RESULTS
Treatment of MCF-7 cells with various concentrations of britannin remarkably hindered the viability of these cells compared to the controls. This compound significantly elevated the expression of pro-apoptotic caspase-3 but did not influence the levels of anti-apoptotic and . Britannin decreased the levels of phosphorylated forms of JAK2 and STAT3 proteins causing the blockage of the JAK/STAT pathway. Four autophagy factors expressions, including ATG4, ATG5, Beclin1, and LCIII, were reduced due to the effect of britannin on MCF-7 cells.
CONCLUSION
Britannin triggered apoptosis in MCF-7 cells by a mechanism that led to the blockade of the JAK/STAT pathway. Moreover, britannin prohibited autophagy in these cancer cells. This may suggest britannin as an agent for the suppression of breast tumors or as an adjutant for the enhancement of anti-breast cancer drugs effect.
PubMed: 38948174
DOI: 10.22038/AJP.2023.22995 -
Oncology Research 2024Breast cancer, a predominant global health issue, requires ongoing exploration of new therapeutic strategies. Palbociclib (PAL), a well-known cyclin-dependent kinase...
Breast cancer, a predominant global health issue, requires ongoing exploration of new therapeutic strategies. Palbociclib (PAL), a well-known cyclin-dependent kinase (CDK) inhibitor, plays a critical role in breast cancer treatment. While its efficacy is recognized, the interplay between PAL and cellular autophagy, particularly in the context of the RAF/MEK/ERK signaling pathway, remains insufficiently explored. This study investigates PAL's inhibitory effects on breast cancer using both (MCF7 and MDA-MB-468 cells) and (tumor-bearing nude mice) models. Aimed at elucidating the impact of PAL on autophagic processes and exploring the potential of combining it with trametinib (TRA), an MEK inhibitor, our research seeks to address the challenge of PAL-induced drug resistance. Our findings reveal that PAL significantly decreases the viability of MCF7 and MDA-MB-468 cells and reduces tumor size in mice while showing minimal cytotoxicity in MCF10A cells. However, PAL also induces protective autophagy, potentially leading to drug resistance via the RAF/MEK/ERK pathway activation. Introducing TRA effectively neutralized this autophagy, enhancing PAL's anti-tumor efficacy. A combination of PAL and TRA synergistically reduced cell viability and proliferation, and studies showed notable tumor size reduction. In conclusion, the PAL and TRA combination emerges as a promising strategy for overcoming PAL-induced resistance, offering a new horizon in breast cancer treatment.
Topics: Humans; Animals; Autophagy; Breast Neoplasms; Pyridines; Pyridones; Female; Pyrimidinones; Mice; Xenograft Model Antitumor Assays; Piperazines; Cell Line, Tumor; Drug Resistance, Neoplasm; Cell Proliferation; Drug Synergism; Antineoplastic Combined Chemotherapy Protocols; Mice, Nude; MAP Kinase Signaling System; Protein Kinase Inhibitors; Cell Survival; MCF-7 Cells
PubMed: 38948022
DOI: 10.32604/or.2024.046139 -
Heliyon Jun 2024New 3-furan-1-thiophene-based chalcones were synthesized, characterized and pharmacologically evaluated as antibacterial and anticancer agents against two bacterial...
New 3-furan-1-thiophene-based chalcones were synthesized, characterized and pharmacologically evaluated as antibacterial and anticancer agents against two bacterial species; Gram-positive () and Gram-negative (). All tested final compounds were active against the two bacterial species; and . Especially compound AM4 showed large inhibition zone (27.13 and 23.30 mm), respectively. Using the DPPH assay, the new chalcones were evaluated for their free radical scavenging activity and found to reach up to 90 %, accomplished at a test concentration of 200 μg/mL. Furthermore, the chalcone derivatives were investigated against two breast cell lines; MCF-7 (cancerous) and MCF-10A (non-cancerous). Compound AM4 showed potent anticancer activity (IC = 19.354 μg/mL) in comparison to the other tested chalcone derivatives. study was achieved using the PyRx AutoDock Vina software (0.8) to study the interaction types between the new hits and the binding sites of targeted proteins; glucosamine-6-phosphate synthase and tubulin, the target for antibacterial and anticancer drugs, respectively. Based on the molecular docking results the tested chalcones bind to the active pocket of the respective proteins, which support the results. In conclusion, 3-furan-1-thiophene-based chalcones could serve as new hits in the discovery of novel anticancer and/or antibacterial drugs.
PubMed: 38947436
DOI: 10.1016/j.heliyon.2024.e32257 -
Journal of Pharmacological and... Jun 2024This editorial prefaces the annual themed issue on safety pharmacology (SP) methods which has been published since 2004 in the Journal of Pharmacological and...
This editorial prefaces the annual themed issue on safety pharmacology (SP) methods which has been published since 2004 in the Journal of Pharmacological and Toxicological Methods (JPTM). Here we highlight content derived from the 2023 Safety Pharmacology Society (SPS) meeting held in Brussels, Belgium. The meeting generated 138 abstracts, reproduced in the current volume of JPTM. As in prior years, the manuscripts reflect various areas of innovation in SP including in silico modeling of stroke volume, cardiac output and systemic vascular resistance, computational approaches that compare drug-induced proarrhythmic sensitivity of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), an evaluation of the utility of the corrected J-Tpeak and Tpeak-to-Tend parameters from the ECG as potential proarrhythmia biomarkers, and the applicability of nonclinical concentration-QTc (C-QTc) modeling of data derived from the conduct of the in vivo QTc study as a component of the core battery of safety pharmacology studies.
PubMed: 38945308
DOI: 10.1016/j.vascn.2024.107533 -
Biomacromolecules Jun 2024Rapid proliferation and a faster rate of glycolysis in cancer cells often result in an elevated local temperature (40-43 °C) at the tumor site. Nanoparticles prepared...
Rapid proliferation and a faster rate of glycolysis in cancer cells often result in an elevated local temperature (40-43 °C) at the tumor site. Nanoparticles prepared from polymers with two lower critical solution temperatures (LCSTs) can be utilized to take advantage of this subtle temperature elevation to deliver anticancer drugs preferably to the cancer cells, thereby enhancing the overall therapeutic efficacy and reducing side effects. In this direction, we synthesized -vinyl-2-pyrrolidone (NVP) and substituted NVP (sub-NVP: C-NVP, C-NVP)-based polymers with precisely controlled LCSTs by varying the ratio of NVP and sub-NVP. The first LCST (LCST1) was kept below 37 °C to promote self-assembly, drug loading, and structural stability in physiological conditions and the second LCST (LCST2) was in the range of 40-43 °C to ensure mild hyperthermia-induced drug release. Additionally, covalent attachment of tetraphenylethylene (TPE, AIEgen) resulted in aggregation-induced emission in thermoresponsive micellar nanoparticles in which TPE acted as a Förster Resonance Energy Transfer (FRET) pair with the loaded anticancer drug doxorubicin (DOX). Tracking of FRET-induced fluorescence recovery of TPE molecules was utilized to confirm the real-time thermoresponsive release of DOX from nanoparticles and eventual localization of TPE in the cytoplasm and DOX in the nucleus. cellular studies such as cytotoxicity, cellular uptake, and thermoresponsive drug release showed that the DOX-loaded polymeric nanoparticles were nontoxic to normal cells (HEK-293) but significantly more effective in cancer cells (MCF-7) at 40 °C. To our knowledge, this is the first report of preferential delivery of anticancer drugs only by exploiting the slightly elevated temperature of cancer cells.
PubMed: 38943659
DOI: 10.1021/acs.biomac.4c00572 -
Scientific Reports Jun 2024Breast cancer is a prevalent and significant cause of mortality in women, and manifests as six molecular subtypes. Its further histologic classification into...
Breast cancer is a prevalent and significant cause of mortality in women, and manifests as six molecular subtypes. Its further histologic classification into non-invasive ductal or lobular carcinoma (DCIS) and invasive carcinoma (ILC or IDC) underscores its heterogeneity. The ubiquitin-proteasome system plays a crucial role in breast cancer, with inhibitors targeting the 26S proteasome showing promise in clinical treatment. The Cullin-RING ubiquitin ligases, including CUL3, have direct links to breast cancer. This study focuses on CUL3 as a potential biomarker, leveraging high-throughput sequencing, gene expression profiling, experimental and data analysis tools. Through comprehensive analysis using databases like GEPIA2 and UALCAN, as well as TCGA datasets, CUL3's expression and its association with prognostic values were assessed. Additionally, the impact of CUL3 overexpression was explored in MCF-7 and MDA-MB-231 breast cancer cell lines, revealing distinct differences in molecular and phenotypic characteristics. We further profiled its expression and localization in breast cancer tissues identifying prominent differences between luminal A and TNBC tumors. Conclusively, CUL3 was found to be associated with cell cycle progression, and DNA damage response, exhibiting diverse roles depending on the tumor's molecular type. It exhibits a tendency to act as an oncogene in triple-negative tumors and as a tumor suppressor in luminal A types, suggesting a potential significance in breast cancer progression and therapeutic directions.
Topics: Humans; Cullin Proteins; Female; Prognosis; Breast Neoplasms; Biomarkers, Tumor; Gene Expression Regulation, Neoplastic; Cell Line, Tumor; Gene Expression Profiling; MCF-7 Cells; Triple Negative Breast Neoplasms
PubMed: 38942922
DOI: 10.1038/s41598-024-65692-z -
Environmental Research Jun 2024In present investigation, Carica papaya leaf extract has been employed as a bio-reductant agent in order to synthesize ecologically sustainable bio-coupled gold...
Environmental profiling of gold nanoparticles by flavonoids fractionalization from carrica papaya leaf extract for photocatalytic debasement of organic contaminants and it's cyto-toxic analysis.
In present investigation, Carica papaya leaf extract has been employed as a bio-reductant agent in order to synthesize ecologically sustainable bio-coupled gold nanoparticles. The formation of gold nanoparticles was confirmed based on colour change of solution and its surface plasmon resonance peak measured using UV-Vis Spectrophotometer (UV-Vis). The Morphology and size of nanoparticles were determined using transmission electron microscope (SEM/TEM), and its crystalline structure by X-ray diffraction studies. Surface area was determined via BET isotherm analysis. The elemental composition of Au nanoparticles was developed using the technique of energy dispersive spectroscopy (EDS). Furthermore, FTIR analysis delineated the presence of functional groups present in the samples of the synthesized AuNPs. Thus, the efficiency of bio coupled Au nanoparticles in photo catalytically decomposing methylene blue was examined under the influence of visible light., the lethal MB colorant had been reduced to 95 % Within 90 min. And also 60% TOC removal was recorded after 5 min of degradation reaction, which increased to 99% after 90 min. Furthermore, cytotoxic experiments on Michigan Cancer Foundations-7 (MCF-7) cell lines showed that Au nanoparticles are effective anticancer agents with an IC of 87.2 g/mL on the top of the present work revealed the eco-safety and affordable production of Au nanoparticles from Carica papaya leaf extract, which displayed photocatalytic debasement of organic pollutants and cyto-toxicity effects was investigated.
PubMed: 38942259
DOI: 10.1016/j.envres.2024.119445 -
Journal of Asian Natural Products... Jun 2024The undescribed phosphatidylcholine (), along with twelve known compounds, was isolated from the cultures of white rot fungus PP17-20. In this work the fungus was...
The undescribed phosphatidylcholine (), along with twelve known compounds, was isolated from the cultures of white rot fungus PP17-20. In this work the fungus was cultivated in Yeast-Malt extract medium to explore active compound production. The chemical structures were elucidated on the basis of spectroscopic and HRESIMS data. Several isolated compounds were evaluated for anti-proliferative activity against A549 and MCF-7 cancer cell lines.
PubMed: 38940405
DOI: 10.1080/10286020.2024.2368834