stigmasterol and Lung-Neoplasms

This study aims to investigate the role of stigmasterol in lung cancer. The study aims to investigate the role of stigmasterol in lung cancer and further explore its possible mechanisms.. Cell Counting Kit-8 assay, 5-ethynyl-2-deoxyuridine (EdU), TUNEL and Flow cytometry were conducted to detect the proliferation and apoptosis of lung cancer cell lines. qRT-PCR and western blot were conducted to detect mRNA and protein levels of caspase-3 and caspase-9. In addition, Gene Ontology, STRING, SWISSMODEL, cellular thermal shift assay (CETSA) and Swiss Target Prediction were used to predict the targets of stigmasterol.. Behavioral studies showed that stigmasterol inhibited the proliferation and promoted the apoptosis of lung cancer cells. Further research revealed that retinoic acid-related orphan receptor C (RORC) directly targeted stigmasterol in lung cancer. Interestingly, rescue experiments indicated that RORC overexpression reversed the inhibitory effect of stigmasterol on lung cancer.. In our study, we confirmed the functional role of the stigmasterol-RORC axis in lung cancer progression, which provides a latent target for lung cancer treatment.

Topics: Apoptosis; Caspase 3; Caspase 9; Flow Cytometry; Humans; Lung Neoplasms; Orphan Nuclear Receptors; Receptors, Retinoic Acid; Stigmasterol; Tretinoin

Fucosterol, a sterol isolated from brown algae, has been demonstrated to have anti-cancer properties. However, the effects and underlying molecular mechanism of fucosterol on non-small cell lung cancer remain to be elucidated. In this study, the corresponding targets of fucosterol were obtained from PharmMapper, and NSCLC related targets were gathered from the GeneCards database, and the candidate targets of fucosterol-treated NSCLC were predicted. The mechanism of fucosterol against NSCLC was identified in DAVID6.8 by enrichment analysis of GO and KEGG, and protein-protein interaction data were collected from STRING database. The hub gene GRB2 was further screened out and verified by molecular docking. Moreover, the relationship of GRB2 expression and immune infiltrates were analyzed by the TIMER database. The results of network pharmacology suggest that fucosterol acts against candidate targets, such as MAPK1, EGFR, GRB2, IGF2, MAPK8, and SRC, which regulate biological processes including negative regulation of the apoptotic process, peptidyl-tyrosine phosphorylation, positive regulation of cell proliferation. The Raf/MEK/ERK signaling pathway initiated by GRB2 showed to be significant in treating NSCLC. In conclusion, our study indicates that fucosterol may suppress NSCLC progression by targeting GRB2 activated the Raf/MEK/ERK signaling pathway, which laying a theoretical foundation for further research and providing scientific support for the development of new drugs.

Topics: Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; GRB2 Adaptor Protein; Humans; Lung Neoplasms; MAP Kinase Signaling System; Molecular Docking Simulation; Network Pharmacology; Signal Transduction; Stigmasterol

Despite several phytochemical studies of Premna serratifolia Linn. (Verbenaceae), the isolation of active constituents of this plant remains to be explored.. The study isolates cytotoxic terpenoids and steroids from the leaves of Premna serratifolia.. Unsaponifiable matter of hexane soluble fraction obtained from methanol extract was subjected to isolation by column chromatography and preparative TLC. Three compounds PS-01 A, PS-01B and PS-02 A were isolated. PS-01 A and PS-01B were identified by comparative TLC with authentic marker compounds followed by NMR analysis. Further PS-01B was analyzed by HR-GCMS. PS-02 A was subjected to HR-LCMS. All isolated compounds/fractions were evaluated for cytotoxic activity by BSL bioassay and using cell lines A549, HepG2 and L6.. Bioactivity guided fractionation of Premna serratifolia leaves succeeded into isolation of two terpenoids and one steroid compound with significant cytotoxic activity. Here we report the isolation of these cytotoxic terpenoids/steroids from this plant for the first time which could be developed as anticancer agents.

Topics: A549 Cells; Animals; Antineoplastic Agents, Phytogenic; Cell Survival; Chromatography, Thin Layer; Dose-Response Relationship, Drug; Gas Chromatography-Mass Spectrometry; Hep G2 Cells; Hexanes; Humans; Inhibitory Concentration 50; Liver Neoplasms; Lung Neoplasms; Magnetic Resonance Spectroscopy; Methanol; Muscle Fibers, Skeletal; Oleanolic Acid; Phytotherapy; Plant Extracts; Plant Leaves; Plants, Medicinal; Rats; Solvents; Stigmasterol; Verbenaceae

Two new diterpenoids, 14,18-dihydroxyabieta-8,11,13-trien-7-one (1) and 13-acetyl-14,18-dihydroxy-podocarpa-8,11,13-triene (2), together with eight known compounds, i.e., gaultheric acid (3), vanillic acid (4), 4-hydroxybenzoic acid (5), cinnamic acid (6), stearic acid (7), palmitic acid (8), beta-sitosterol (9), and stigmasterol (10), were isolated from the MeOH extract of the whole plant of Gaultheria itoana Hayata (Ericaceae). The structures of the new constituents were elucidated by spectroscopic methods (UV, IR, and 1D- and 2D-NMR) and by mass spectrometry (HR-ESI-MS). Among them, 1 and 2 were demonstrated to exhibit significant cytotoxic activity against the LNCaP cell line.

Topics: Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Cinnamates; Diterpenes; Gaultheria; Humans; Lung Neoplasms; Magnetic Resonance Spectroscopy; Methanol; Molecular Structure; Palmitic Acid; Parabens; Plant Extracts; Sitosterols; Spectrometry, Mass, Electrospray Ionization; Stearic Acids; Stigmasterol; Vanillic Acid