Isorhamnetin Inhibits Proliferation and Invasion and Induces Apoptosis Through the Mitochondria‑Dependent Apoptosis in Human Gastric Cancer Cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA842914 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19428841_1.fastq.gz | Fastqsanger.gz | |||
| SRR19428841_2.fastq.gz | Fastqsanger.gz | |||
| SRR19428842_1.fastq.gz | Fastqsanger.gz | |||
| SRR19428842_2.fastq.gz | Fastqsanger.gz | |||
| SRR19428843_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 8 |
Similar Datasets
Project description:The major treatment strategies for gastric cancer (GC) including surgery, chemotherapy, and molecular-targeted therapy are limited by tumor recurrence and chemoresistance. Isorhamnetin (ISO) derives from the total flavones of Hippophae rhamnoides L. and has been used as potential antitumor medicine in several types of cancer. However, the antitumor effect of ISO on GC cells remains unclear. Here, we investigated the effects of ISO on two types of GC cells and explored its apoptotic mechanisms underlying such effects. The transcriptomic analysis of ISO-treated GC cells enriched multiple targets on cell growth and apoptosis. The CCK-8, colony formation and morphology observation assays demonstrated that ISO treatment significantly inhibited the growth and proliferation of GC cells in time- and dose-dependent manners. In addition, we also found that ISO treatment inhibited cell migration and invasion. Furthermore, ISO increased TUNEL positive apoptotic bodies as well as severe cell apoptosis. Intriguingly, ISO treatment significantly increased the expression of mitochondria-associated Bax/Bcl-2, cytosolic Cytochrome c and activated the cleavage of Caspase-3 and PARP, followed by severe reduction of mitochondrial potential. Moreover, the apoptosis of ISO-treated GC cells was blocked by the specific inhibitor of Caspase-3. Therefore, we demonstrated that ISO could induce apoptosis of GC cells through mitochondria-dependent apoptotic pathway. In summary, we reported for the first time the antitumor function of ISO in GC via intervening apoptosis, indicating a potential application in GC therapy.
2022-05-30 | GSE204967 | GEO
Project description:Derivates of natural products have been wildly utilized in the treatment of malignant tumors. Isorhamnetin (ISO), a most important active ingredient derived from flavonoids, shows great potential in tumor therapy. However, the therapeutic effects of ISO on gastric cancer (GC) remain unclear. Here, we demonstrate that ISO treatment dramatically inhibited the proliferation of two types of GC cells (AGS-1 and HGC-27) both in vitro and in vivo in time- and dose-dependent manners. These results are consistent with the transcriptomic analysis of ISO-treated GC cells, which yielded hundreds of differentially expressed genes that were enriched with cell growth and apoptosis. Mechanically, ISO treatment initiated the activation of caspase-3 cascade and elevated the expression of mitochondria-associated Bax/Bcl-2, cytosolic cytochrome c, followed by the activation of the cleavage of caspase-3 as well as poly ADP-ribose polymerase (PARP), resulting in the severe reduction of the mitochondrial potential and the accumulation of reactive oxygen species (ROS), while pre-treatment of the caspase-3 inhibitor could block the anti-tumor effect. Therefore, these results indicate that ISO treatment induces the apoptosis of GC cells through the mitochondria-dependent apoptotic pathway, providing a potential strategy for clinical GC therapy.
| S-EPMC9415531 | biostudies-literature
Project description:Inactivating mutations in SMARCA4 and concurrent epigenetic silencing of SMARCA2 characterize subsets of ovarian and lung cancers. Concomitant loss of these key subunits of SWI/SNF chromatin remodeling complexes in both cancers is associated with chemotherapy resistance and poor prognosis. Here, we discover that SMARCA4/2 loss inhibits chemotherapy-induced apoptosis through disrupting intracellular organelle calcium ion (Ca2+) release in these cancers. By restricting chromatin accessibility to ITPR3, encoding Ca2+ channel IP3R3, SMARCA4/2 deficiency causes reduced IP3R3 expression leading to impaired Ca2+ transfer from the endoplasmic reticulum to mitochondria required for apoptosis induction. Reactivation of SMARCA2 by a histone deacetylase inhibitor rescues IP3R3 expression and enhances cisplatin response in SMARCA4/2-deficient cancer cells both in vitro and in vivo. Our findings elucidate the contribution of SMARCA4/2 to Ca2+-dependent apoptosis induction, which may be exploited to enhance chemotherapy response in SMARCA4/2-deficient cancers.
| EGAS00001005448 | EGA
Project description:Gastric cancer (GC) is a lethal malignancy and the second most common cause of cancer-related deaths. Although treatment options such as chemotherapy, radiotherapy, and surgery have led to a decline in the mortality rate due to GC, chemoresistance remains as one of the major causes for poor prognosis and high recurrence rate. In this study, we investigated the potential effects of isorhamnetin (IH), a 3'-O-methylated metabolite of quercetin on the peroxisome proliferator-activated receptor ? (PPAR-?) signaling cascade using proteomics technology platform, GC cell lines, and xenograft mice model. We observed that IH exerted a strong antiproliferative effect and increased cytotoxicity in combination with chemotherapeutic drugs. IH also inhibited the migratory/invasive properties of GC cells, which could be reversed in the presence of PPAR-? inhibitor. We found that IH increased PPAR-? activity and modulated the expression of PPAR-? regulated genes in GC cells. Also, the increase in PPAR-? activity was reversed in the presence of PPAR-?-specific inhibitor and a mutated PPAR-? dominant negative plasmid, supporting our hypothesis that IH can act as a ligand of PPAR-?. Using molecular docking analysis, we demonstrate that IH formed interactions with seven polar residues and six nonpolar residues within the ligand-binding pocket of PPAR-? that are reported to be critical for its activity and could competitively bind to PPAR-?. IH significantly increased the expression of PPAR-? in tumor tissues obtained from xenograft model of GC. Overall, our findings clearly indicate that antitumor effects of IH may be mediated through modulation of the PPAR-? activation pathway in GC.
| S-EPMC3488073 | biostudies-literature
Project description:Gene expression profiling reveals a potential role of isorhamnetin in the mitigation of NASH features including steatosis, liver injury, and fibrosis Microarray gene expression profiling was conducted for technical replicates of healthy liver as control (CTL), NASH-induced (NASH), NASH-induced treated with isorhamnetin for 14 days (50 mg/kg of body weight) (NASH+ISO) liver tissues to identify its effect in the regulation of pathways involved in pathologic features of NASH.
2019-09-19 | GSE137635 | GEO
Project description:The unique metabolic profile of most cancers (aerobic glycolysis) might confer apoptosis-resistance and be therapeutically targeted. Compared to normal cells, several human cancers have high mitochondrial membrane potential and low expression of the K+ channel Kv1.5, both contributing to apoptosis-resistance. Dichloroacetate (DCA), an inhibitor of the mitochondrial pyruvate dehydrogenase kinase (PDK), shifts metabolism from glycolysis to glucose oxidation, decreases mitochondrial membrane potential, increases mitochondrial-H2O2 and activates Kv channels in all cancer, but not normal cells; DCA upregulates Kv1.5 by an NFAT1-dependent mechanism. DCA induces apoptosis, decreases proliferation and tumor growth in vitro and in vivo, without apparent toxicity. Molecular inhibition of PDK2 by siRNA mimics DCA. The mitochondria-NFAT-Kv axis and PDK are important therapeutic targets in cancer; the orally available DCA is a novel selective anticancer agent. Keywords: treatment
2006-10-11 | GSE6014 | GEO
Project description:Liquid storage of spermatozoa is important for artificial insemination and herd genetic breeding. However, the extending time of storage inducing rapid decline of spermatozoa quality limits the development of this technology. The molecular mechanisms underlying liquid storage of spermatozoa remain largely unexplored. In this study, the effects of liquid storage on functional quality of spermatozoa were assessed in goat (Capra hircus). The time-dependent decline of spermatozoa motility showed a strong correlation with the significant increase of apoptosis. Moreover, apoptosis-related ultrastructural changes were observed, especially the defect in mitochondria. Meanwhile, significant decrease of mitochondrial membrane potential and expression changes of mitochondrial apoptosis-related proteins indicated mitochondrial dysfunction and activation of mitochondrial apoptotic pathway. Notably, the abnormal high level of reactive oxygen species (ROS) caused by liquid storage resulted in the oxidative damage to mitochondria and accelerated mitochondria-dependent apoptosis, which was demonstrated by addition of ROS scavenger N-acetylcysteine. Furthermore, critical differentially expressed proteins involved in mitochondria-dependent apoptosis and antioxidant defense were identified and profiled by quantitative proteomic analysis, facilitating the understanding of molecular regulation of ROS-induced mitochondria-dependent apoptosis. These outcomes provide insights into the mechanisms underlying liquid storage of goat spermatozoa and enhance the progress of semen storage technology.
2019-11-12 | PXD014609 | Pride
Project description:Gastric cancer (GC) is a heterogeneous disease whose development is accompanied by alterations in a variety of pathogenic genes. The phospholipase C Delta 3 enzyme is a member of the phospholipase C family, which controls substance transport between cells in the body. However, its role in gastric cancer has not been discovered. The purpose of this study was to investigate the expression and mechanism of action of PLCD3 in connection to gastric cancer. By Western blot analysis and immunohistochemistry, PLCD3 mRNA and protein expression levels were measured, with high PLCD3 expression suggesting poor prognosis. In N87 and HGC-27 cells, the silencing of PLCD3 using small interfering RNA effectively induced apoptosis and inhibited tumor cell proliferation, invasion, and migration. Conversely, overexpression of PLCD3 using overexpressed plasmids inhibited apoptosis in AGS and BGC-823 cells and promoted proliferation, migration, and invasion. In order to investigate the underlying mechanisms, we conducted further analysis of PLCD3, which indicates that this protein is closely related to the cell cycle and EMT. Additionally, we found that overexpression of PLCD3 inhibits apoptosis and promotes the development of GC cells through JAK2/STAT3 signaling. In conclusion, PLCD3 inhibits apoptosis and promotes proliferation, invasion, and migration, which indicated that PLCD3 might serve as a therapeutic target for gastric cancer.
| S-EPMC10837395 | biostudies-literature
Project description:The unique metabolic profile of most cancers (aerobic glycolysis) might confer apoptosis-resistance and be therapeutically targeted. Compared to normal cells, several human cancers have high mitochondrial membrane potential and low expression of the K+ channel Kv1.5, both contributing to apoptosis-resistance. Dichloroacetate (DCA), an inhibitor of the mitochondrial pyruvate dehydrogenase kinase (PDK), shifts metabolism from glycolysis to glucose oxidation, decreases mitochondrial membrane potential, increases mitochondrial-H2O2 and activates Kv channels in all cancer, but not normal cells; DCA upregulates Kv1.5 by an NFAT1-dependent mechanism. DCA induces apoptosis, decreases proliferation and tumor growth in vitro and in vivo, without apparent toxicity. Molecular inhibition of PDK2 by siRNA mimics DCA. The mitochondria-NFAT-Kv axis and PDK are important therapeutic targets in cancer; the orally available DCA is a novel selective anticancer agent. Experiment Overall Design: lung carcinoma and brain glioblastoma cells were analalyzed, with microarrays run both for control and treatment with DCA
2008-06-14 | E-GEOD-6014 | biostudies-arrayexpress
Project description:TLR3 overexpression induces invasion of prostate cancer cells, whereas its activation triggers apoptosis
| PRJNA771529 | ENA