Mechanism Study of Ganoderma Triterpenoid Extracts Inhibiting Colon Cancer Stemness and Migration Capacity
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE308900 | GEO | 2025/09/30
REPOSITORIES: GEO
Similar Datasets
Project description:Mechanism Study of Ganoderma Triterpenoid Extracts Inhibiting Colon Cancer Stemness and Migration Capacity
| PRJNA1333364 | ENA
Project description:Background. Clinical data and animal models support an association between postoperative inflammatory response and the risk of colorectal cancer recurrence. Our aim was to evaluate postoperative peritoneal inflammation and its impact on cultured colon cancer cells' migration capacity. Methods. 23 patients undergoing elective colorectal resection with uneventful recovery were prospectively enrolled. Patients were operated on for both malignant and benign etiologies. Peritoneal fluids collected at surgery initiation and after surgery were evaluated for their effect on migration potential of human colon cancer cells using an in vitro scratch assay and on TNF-α, IL-1β, IL-6, and IL-10 levels using bead-based fluorokine-linked multianalyte profiling. Results. Postoperative peritoneal fluid from all patients increased the migration capacity of colon cancer cells compared to preoperative levels. This effect was significant during the first two postoperative days and decreased thereafter. The increase in colon cancer cell migration capacity correlated with increased levels of peritoneal TNF-α and IL-10. Conclusion. In this pilot study, we have demonstrated that the intraperitoneal environment following colorectal resection significantly enhances colon cancer cells migration capacity. This effect is associated with postoperative intra-abdominal cytokines level. A larger scale study in colorectal cancer patients is needed in order to correlate these findings with perioperative parameters and clinical outcome.
| S-EPMC4706905 | biostudies-literature
Project description:Glioblastoma multiforme (GBM) is the most malignant brain tumor and is associated with poor prognosis due to its thorny localization, lack of efficacious therapies and complex biology. Among the numerous pathways driving GBM biology studied so far, PTEN/phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) signaling plays a pivotal role, as it controls cell survival, proliferation and metabolism and is involved in stem cell maintenance. In front of recent and numerous evidences highlighting mTOR upregulation in GBM, all the strategies developed to inhibit this pathway have been substantially unsuccessful. Our study focused on mTOR complex 2 (mTORC2) to understand its involvement in GBM cell growth, proliferation, migration and invasiveness. We utilized an in vitro model, characterized by various genetic alterations (i.e., GL15, U257, U87MG and U118MG cell lines) in order to achieve the clonal heterogeneity observed in vivo. Additionally, being the U87MG cell line endowed with glioblastoma stem cells (GSCs), we also investigated the role of the PTEN/PI3K/AKT/mTOR pathway in this specific cell population, which is responsible for GBM relapse. We provide further insights that explain the reasons for the failure of numerous clinical trials conducted to date targeting PI3K or mTOR complex 1 (mTORC1) with rapamycin and its analogs. Additionally, we show that mTORC2 might represent a potential clinically valuable target for GBM treatment, as proliferation, migration and GSC maintenance appear to be mTORC2-dependent. In this context, we demonstrate that the novel ATP-competitive mTOR inhibitor PP242 effectively targets both mTORC1 and mTORC2 activation and counteracts cell proliferation via the induction of high autophagy levels, besides reducing cell migration, invasiveness and stemness properties.
| S-EPMC5902688 | biostudies-literature
Project description:Defining new therapeutic strategies to overcome therapy resistance due to tumor heterogeneity in colon cancer is challenging. One option is to explore the molecular profile of aggressive disseminating tumor cells. The cytoskeleton-associated Death-associated protein kinase (DAPK) is involved in the cross talk between tumor and immune cells at the invasion front of colorectal cancer. Here dedifferentiated tumor cells histologically defined as tumor budding are associated with a high risk of metastasis and poor prognosis. Analyzing samples from 144 colorectal cancer patients we investigated immunhistochemical DAPK expression in different tumor regions such as center, invasion front, and buds. Functional consequences for tumor aggressiveness were studied in a panel of colon tumor cell lines using different migration, wound healing, and invasion assays. DAPK levels were experimentally modified by siRNA transfection and overexpression as well as inhibitor treatments. We found that DAPK expression was reduced towards the invasion front and was nearly absent in tumor buds. Applying the ECIS system with HCT116 and HCT116 stable lentiviral DAPK knock down cells (HCTshDAPK) we identified an important role for DAPK in decreasing the migratory capacity whereas proliferation was not affected. Furthermore, the migration pattern differed with HCTshDAPK cells showing a cluster-like migration of tumor cell groups. DAPK inhibitor treatment revealed that the migration rate was independent of DAPK's catalytic activity. Modulation of DAPK expression level in SW480 and DLD1 colorectal cancer cells significantly influenced wound closure rate. DAPK seems to be a major player that influences the migratory capability of disseminating tumor cells and possibly affects the dynamic interface between pro- and anti-survival factors at the invasion front of colorectal cancer. This interesting and new finding requires further evaluation.
| S-EPMC4742210 | biostudies-literature
Project description:Androgen-independent prostate cancer accounts for mortality in the world. In this study, various extracts of a medical fungus dubbed Ganoderma formosanum were screened for inhibition of DU145 cells, an androgen-independent prostate cancer cell line. Results demonstrated that both hexane (GF-EH) and butanol (GF-EB) fraction of G. formosanum ethanol extract inhibited DU145 cell viability in a dose-dependent manner. GF-EH induced cell-cycle arrest in G1 phase of DU145 cells via downregulation of cyclin E2 protein expression. In addition, GF-EB triggered extrinsic apoptosis of DU145 cells by activating caspase 3 gene expression resulting in programed cell death. Above all, both GF-EH and GF-EB show lower toxicity to normal human fibroblast cell line compared to DU145 cell, implying that they possess specific drug action on cancer cells. This study provides a molecular basis of G. formosanum extract as a potential ingredient for treatment of androgen-independent prostate cancer.
| S-EPMC10635139 | biostudies-literature
Project description:Of 33 seed extracts examined, 12 inhibited protein synthesis in a rabbit reticulocyte lysate. This activity seems to be due to a protein, since (i) it was recovered with the (NH4)2SO4 precipitate, (ii) it was retained by dialysis membranes, and (iii) in all cases but one was destroyed by boiling. Only the extracts from the seeds of Adenia digitata and, to a lower extent, of Euonymus europaeus inhibited protein synthesis in intact cells.
| S-EPMC1161594 | biostudies-other
Project description:In this bioprospecting study the biological activities of extracts of the in vitro culture of Ganoderma Mexican strains were evaluated. The extracts were tested by the Sulforhodamine B staining method for antiproliferative activity and the plate microdilution method for antibacterial activity. Extracts that proved bioactive in these two activities, the antioxidant activity (Galvinoxyl, ABTS, and DPPH) and total phenolic contents (Folin-Ciocalteu) were additionally determined, as well as acute toxicity (Artemia franciscana). In the antiproliferative activity Ganoderma curtisii strain (GH-16-015) obtained a remarkable value of GI50 ≤ 50 µg/mL against tumor lines: A549, HBL-100, HeLa, and T-47D. G. curtisii strains (GH-16-012 and GH-16-015) showed MIC values = 500 µg/mL against Staphylococcus aureus. G. curtisii strain (GH-16-012) almost reduced by 50% the radical Galvinoxyl. Finally, G. curtisii strain (GH-16-023) presented the lowest level of toxicity with a LC50 of 490.881 µg/mL against A. franciscana. These results support the potential medicinal effects of Mexican strains of G. curtisii.
| S-EPMC8144262 | biostudies-literature
Project description:Ganoderma lucidum (GL) is a prominent medicinal mushroom in traditional Chinese medicine, known for its potent antitumor properties. This study aimed to illustrate the efficacy of GL extracts (GLE) on treating endometrial cancer (EC) and explore the underlying mechanisms via network pharmacology and experimental validation. Network pharmacological analysis was conducted to explore the therapeutic efficacy and mechanisms of GL on EC. In vitro experimental validation was performed on human endometrial cancer cell lines HEC-1-A and KLE. Network pharmacology revealed that key targets of GL against EC were primarily associated with the Rap1 signaling pathway. In in vitro experiments, GLE or GGTI-298 (a GTPase inhibitor) treatment inhibited cell proliferation and migration, promoted cell apoptosis, increased caspase-3 level, and arrested cell cycle in G1 phase in HEC-1-A and KLE cells. GLE increased the protein expression of Rap1-GTP, p-AKT, and p-ERK2 in HEC-1-A and KLE cells. Moreover, GGTI-298 enhanced the effects of GLE on suppressing the malignant progression of EC cells and on activating Rap1 signaling pathway. GLE inhibited the malignant progression of EC cells probably via activating the Rap1 signaling pathway.
| S-EPMC11217070 | biostudies-literature
Project description:Finger millet (Eleusine coracana) contains high levels of calcium and polyphenols, which have a variety of beneficial functions. We tested the hypothesis that finger millet ethanol extracts (FEs) have an antihypertensive effect in spontaneously hypertensive rats (SHRs). The study groups were assigned as follows: (1) Wistar Kyoto rats (normal); (2) SHRs treated with saline (negative control); (3) SHRs treated with captopril 50 mg/kg bw (positive control); (4) SHRs treated with FE 250 mg/kg bw (FE250); and (5) SHRs treated with FE 500 mg/kg bw (FE500). FE supplementation improved the lipid profiles, including the triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels, without deterioration in liver function. The thiobarbituric acid reactive substance concentration and superoxide dismutase activity significantly improved after the application of FE250 and FE500. Interestingly, FE250 and FE500 application dramatically reduced the systolic blood pressure. FE supplementation exhibited powerful control over the renin-angiotensin system by reducing the angiotensin-converting enzyme levels and renin mRNA expression in the kidney. Additionally, FE500 application ameliorated vascular remodeling, reversed the thickening media, and decreased the media thickness/lumen diameter ratio of the aorta. These results imply that FEs are a potent antihypertensive nutraceutical for regulating the renin-angiotensin system and simultaneously inhibiting oxidative stress.
| S-EPMC8614972 | biostudies-literature
Project description:Disruption of microRNA (miRNA) expression patterns is now being recognized as a hallmark of human cancer. The causes of these altered profiles are diverse, and, among them, we found the existence of defects in the miRNA processing machinery. However, little is known about how these alterations affect the biology of the underlying tumors. Herein, we show that colorectal cancer cells with an impairment in DICER1, a major miRNA biogenesis gene, undergo enrichment of tumor stemness features and an epithelial-to-mesenchymal transition. These phenotypes are associated with the downregulation of miRNAs, such as miR-34a, miR-126 and those of the miR-200 family, that target critical coding genes in these pathways. Most importantly, DICER1 impairment also induces the acquisition of a greater capacity for tumor initiation and metastasis, two properties associated with cancer stem cells.
| S-EPMC4114136 | biostudies-literature