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Environmental Science and Pollution... Jul 2023Phytol (Pyt), a diterpenoid, possesses many important bioactivities. This study evaluates the anticancer effects of Pyt on sarcoma 180 (S-180) and human leukemia (HL-60)...
Phytol (Pyt), a diterpenoid, possesses many important bioactivities. This study evaluates the anticancer effects of Pyt on sarcoma 180 (S-180) and human leukemia (HL-60) cell lines. For this purpose, cells were treated with Pyt (4.72, 7.08, or 14.16 μM) and a cell viability assay was performed. Additionally, the alkaline comet assay and micronucleus test with cytokinesis were also performed using doxorubicin (6 μM) and hydrogen peroxide (10 mM) as positive controls and stressors, respectively. Results revealed that Pyt significantly reduced the viability and rate of division in S-180 and HL-60 cells with IC values of 18.98 ± 3.79 and 1.17 ± 0.34 μM, respectively. Pyt at 14.16 μM exerted aneugenic and/or clastogenic effects in S-180 and HL-60 cells, where the number of micronuclei and other nuclear abnormalities (e.g., nucleoplasmic bridges and nuclear buds) were frequently observed. Moreover, Pyt at all concentrations induced apoptosis and showed necrosis at 14.16 μM, suggesting its anticancer effects on the tested cancer cell lines. Taken together, Pyt showed promising anticancer effects, possibly through inducing apoptosis and necrosis mechanisms, and it exerted aneugenic and/or clastogenic effects on the S-180 and HL-60 cell lines.
Topics: Animals; Humans; HL-60 Cells; Sarcoma 180; Phytol; Apoptosis; Necrosis; Micronucleus Tests; Sarcoma
PubMed: 37308630
DOI: 10.1007/s11356-023-28036-4 -
Journal of Asian Natural Products... May 2021Two new pyrrolizidine alkaloids, sclerwalins A and B ( and ), and one known 9-O-E-hydroxysenecioylretronecine () were first isolated from the seeds of . Their chemical...
Two new pyrrolizidine alkaloids, sclerwalins A and B ( and ), and one known 9-O-E-hydroxysenecioylretronecine () were first isolated from the seeds of . Their chemical structures were elucidated by extensive 1 D NMR and 2 D NMR (HSQC, HMBC, COSY, and ROESY), MS and IR spectra. Cytotoxicities of all isolates were evaluated against five human tumor cell lines (HL-60, A-549, SMMC-7721, MCF-7 and SW480).[Formula: see text].
Topics: Cell Line, Tumor; HL-60 Cells; Humans; Molecular Structure; Pyrrolizidine Alkaloids; Seeds
PubMed: 32228193
DOI: 10.1080/10286020.2020.1740919 -
BMC Cancer May 2023Leukemic cell metabolism plays significant roles in their proliferation and survival. These metabolic adaptations are under regulation by different factors. Programmed...
BACKGROUND
Leukemic cell metabolism plays significant roles in their proliferation and survival. These metabolic adaptations are under regulation by different factors. Programmed Death Ligand -1 (CD-274) is one of the immune checkpoint ligands that do not only cause the immune escape of cancer cells, but also have some intracellular effects in these cells. PD-L1 is overexpressed on leukemic stem cells and relates with poor prognosis of AML. In this study, we investigated effects of PD-L1 stimulation on critical metabolic pathways of glucose and fatty acid metabolisms that have important roles in proliferation and survival of leukemic cells.
METHODS
After confirmation of PD-L1 expression by flow cytometry assay, we used recombinant protein PD-1 for stimulation of the PD-L1 on two AML cell lines, HL-60 and THP-1. Then we examined the effect of PD-L1 stimulation on glucose and fatty acid metabolism in cells at the genomic and metabolomic levels in a time dependent manner. We investigated expression changes of rate limiting enzymes of theses metabolic pathways (G6PD, HK-2, CPT1A, ATGL1 and ACC1) by qRT-PCR and also the relative abundance changes of free fatty acids of medium by GC.
RESULTS
We identified a correlation between PD-L1 stimulation and both fatty acid and glucose metabolism. The PD-L1 stimulated cells showed an influence in the pentose phosphate pathway and glycolysis by increasing expression of G6PD and HK-2 (P value = 0.0001). Furthermore, PD-L1 promoted fatty acid β-oxidation by increasing expression of CPT1A (P value = 0.0001), however, their fatty acid synthesis was decreased by reduction of ACC1 expression (P value = 0.0001).
CONCLUSION
We found that PD-L1 can promote proliferation and survival of AML stem cells probably through some metabolic changes in leukemic cells. Pentose phosphate pathway that has a critical role in cell proliferation and fatty acids β-oxidation that promote cell survival, both are increased by PD-L1 stimulation on AML cells.
Topics: Humans; B7-H1 Antigen; Glucose; Leukemia, Myeloid, Acute; HL-60 Cells; Cell Proliferation
PubMed: 37193972
DOI: 10.1186/s12885-023-10947-7 -
FASEB Journal : Official Publication of... Jan 2023The G protein-coupled receptors, GPR43 (free fatty acid receptor 2, FFA2) and GPR41 (free fatty acid receptor 3, FFA3), are activated by short-chain fatty acids produced...
The G protein-coupled receptors, GPR43 (free fatty acid receptor 2, FFA2) and GPR41 (free fatty acid receptor 3, FFA3), are activated by short-chain fatty acids produced under various conditions, including microbial fermentation of carbohydrates. Previous studies have implicated this receptor energy homeostasis and immune responses as well as in cell growth arrest and apoptosis. Here, we observed the expression of both receptors in human blood cells and a remarkable enhancement in leukemia cell lines (HL-60, U937, and THP-1 cells) during differentiation. A reporter assay revealed that GPR43 is coupled with Gα and Gα and is constitutively active without any stimuli. Specific blockers of GPR43, GLPG0974 and CATPB function as inverse agonists because treatment with these compounds significantly reduces constitutive activity. In HL-60 cells, enhanced expression of GPR43 led to growth arrest through Gα . In addition, the blockage of GPR43 activity in these cells significantly impaired their adherent properties due to the reduction of adhesion molecules. We further revealed that enhanced GPR43 activity induces F-actin formation. However, the activity of GPR43 did not contribute to butyrate-induced apoptosis in differentiated HL-60 cells because of the ineffectiveness of the inverse agonist on cell death. Collectively, these results suggest that GPR43, which possesses constitutive activity, is crucial for growth arrest, followed by the proper differentiation of leukocytes.
Topics: Humans; Fatty Acids, Volatile; Leukocytes; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Cell Differentiation; HL-60 Cells
PubMed: 36468834
DOI: 10.1096/fj.202201591R -
Natural Product Research May 2024Bioassay-guided isolation of the stems of led to one new adamantane-type polycyclic polyprenylated acylphloroglucinols (PPAPs), (-)-garpauvinin A (), and four known...
Bioassay-guided isolation of the stems of led to one new adamantane-type polycyclic polyprenylated acylphloroglucinols (PPAPs), (-)-garpauvinin A (), and four known analogues (). The structure and absolute configuration of was established spectroscopic techniques and ECD method. All the isolates displayed moderate antiproliferative activity against HL-60, PC-3 and Caco-2 human cancer cell lines with IC values ranging from 0.81 to 19.92 μM, and exhibited low toxicity on WPMY-1 normal human cells, showing selectivity between normal and malignant prostate cells. The biosynthetic pathways of the isolated PPAPs were proposed.
Topics: Humans; Molecular Structure; Caco-2 Cells; Garcinia; HL-60 Cells; Phloroglucinol; Hypericum
PubMed: 37234037
DOI: 10.1080/14786419.2023.2217469 -
Chinese Journal of Natural Medicines Feb 2024This study reports the isolation of four new β-carboline alkaloids (1-4) and six previously identified alkaloids (5-10) from the roots of Peganum harmala L. Among these...
This study reports the isolation of four new β-carboline alkaloids (1-4) and six previously identified alkaloids (5-10) from the roots of Peganum harmala L. Among these compounds, 1 and 2 were characterized as rare β-carboline-quinazoline dimers exhibiting axial chirality. Compound 3 possessed a unique 6/5/6/7 tetracyclic ring system with an azepine ring, and compound 4 was a novel annomontine β-carboline. The structures of these compounds were elucidated by spectroscopic data and quantum mechanical calculations. The biosynthetic pathways of 1-3 were proposed. Additionally, the cytotoxicity of some isolates against four cancer cell lines (HL-60, A549, MDA-MB-231, and DU145) was evaluated. Notably, compound 4 exhibited significant cytotoxicity against HL-60, A549, and DU145 cells with IC values of 12.39, 12.80, and 30.65 μmol·L, respectively. Furthermore, compound 2 demonstrated selective cytotoxicity against HL-60 cells with an IC value of 17.32 μmol·L.
Topics: Humans; Peganum; Alkaloids; Carbolines; HL-60 Cells
PubMed: 38342569
DOI: 10.1016/S1875-5364(24)60583-2 -
Lab on a Chip Jan 2019On-chip high-throughput phenotyping of single cells has gained a lot of interest recently due to the discrimination capability of label-free biomarkers such as...
On-chip high-throughput phenotyping of single cells has gained a lot of interest recently due to the discrimination capability of label-free biomarkers such as whole-cell deformability and refractive index. Here we present on-chip refractive index cytometry (RIC) for whole-cell deformability at a high measurement rate. We have further exploited a previously published on-chip optical characterization method which enhances cellular discrimination through the refractive index measurement of single cells. The proposed on-chip RIC can simultaneously probe the cellular refractive index, effective volume and whole-cell deformability while reaching a measurement rate up to 5000 cells per second. Additionally, the relative position of the nucleus inside the cell is reflected by the asymmetry of the measured curve. This particular finding is confirmed by our numerical simulation model and emphasized by a modified cytoskeleton HL-60 cells model. Furthermore, the proposed device discriminated HL-60 derived myeloid cells such as neutrophils, basophils and promyelocytes, which are indistinguishable using flow cytometry. To our knowledge, this is the first integrated device to simultaneously characterize the cellular refractive index and whole-cell deformability, yielding enhanced discrimination of large myeloid cell populations.
Topics: Biomechanical Phenomena; Cell Differentiation; Cytochalasin B; Flow Cytometry; HL-60 Cells; Humans; Lab-On-A-Chip Devices; Mechanical Phenomena; Refractometry; Single-Cell Analysis
PubMed: 30570636
DOI: 10.1039/c8lc00938d -
Chemical & Pharmaceutical Bulletin 2022Five podophyllotoxin derivatives (1-5), two diterpenoids (6 and 7), three diterpenoid xylosides (8-10), a flavanonol glycoside (11), flavonol (12), and biflavonoid (13)...
Five podophyllotoxin derivatives (1-5), two diterpenoids (6 and 7), three diterpenoid xylosides (8-10), a flavanonol glycoside (11), flavonol (12), and biflavonoid (13) were isolated from the leaves of Thujopsis dolabrata (Cupressaceae). Compounds 1, 6, and 8 were named (-)-β-isopeltatin, epi-nootkastatin 2, and acetoxyanticopalol 15-O-β-D-xylopyranoside, respectively. The structures of the isolated compounds were determined based on a detailed analysis of NMR spectroscopic data and through chromatographic and spectroscopic analyses following specific chemical transformations. The isolated compounds (1-5 and 7-11) were evaluated for their cytotoxicity toward HL-60 human promyelocytic leukemia cells and Caki-1 human kidney carcinoma cells. The podophyllotoxin derivatives (1-5) exhibited cytotoxicity against both HL-60 and Caki-1 cells with IC values ranging from 0.00069 to 5.4 µM, and the diterpenoid derivatives (7-10) demonstrated cytotoxicity against HL-60 cells with IC values ranging from 4.5 to 11 µM. HL-60 cells treated with 8 exhibited apoptosis characteristics, such as accumulation of sub-G cells and nuclear chromatin condensation.
Topics: Antineoplastic Agents, Phytogenic; Biflavonoids; Chromatin; Cupressaceae; Diterpenes; Flavonols; Glycosides; HL-60 Cells; Humans; Plant Leaves; Podophyllotoxin
PubMed: 36184455
DOI: 10.1248/cpb.c22-00286 -
Journal of Natural Products Jan 2018Seven new ophiobolins (1-5, 12, and 14) along with the 11 known analogues (6-11, 13, 15-18) were isolated from the ethyl acetate extracts of the liquid and solid...
Seven new ophiobolins (1-5, 12, and 14) along with the 11 known analogues (6-11, 13, 15-18) were isolated from the ethyl acetate extracts of the liquid and solid cultures of the mangrove fungus Aspergillus ustus 094102. The structures including the absolute configurations of the seven new compounds were elucidated by spectroscopic analysis, chemical methods, and quantum ECD calculations. Compounds 4-8 and 11-15 showed cytotoxicities against the G3K, MCF-7, MD-MBA-231, MCF/Adr, A549, and HL-60 human cancer cell lines with the IC values ranging from 0.6 to 9.5 μM.
Topics: A549 Cells; Aspergillus; Cell Line, Tumor; HL-60 Cells; Humans; Inhibitory Concentration 50; MCF-7 Cells; Sesterterpenes
PubMed: 29286660
DOI: 10.1021/acs.jnatprod.7b00335 -
Bioorganic & Medicinal Chemistry Letters Feb 2023A series of 1-O-acyl- and 1-oxo-kamebanin analogues were prepared from kamebanin, isolated from Rabdosia excisa and their cytotoxicity was assayed on HL60 promyelocytic...
A series of 1-O-acyl- and 1-oxo-kamebanin analogues were prepared from kamebanin, isolated from Rabdosia excisa and their cytotoxicity was assayed on HL60 promyelocytic leukemia cells and HCT116 human colon cancer cells. The structure-activity relationship study showed that the presence of 1-O-acyl groups of a C-C carbon chain increased the cytotoxic activity.
Topics: Humans; Antineoplastic Agents; Structure-Activity Relationship; Isodon; HL-60 Cells; HCT116 Cells
PubMed: 36690039
DOI: 10.1016/j.bmcl.2023.129149