Browse
Submit Data
Databases
API
Help

Dataset Information

24 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Synthetic Tryptanthrin Derivatives Induce Cell Cycle Arrest and Apoptosis via Akt and MAPKs in Human Hepatocellular Carcinoma Cells.

ABSTRACT: Trytanthrin, found in Ban-Lan-Gen, is a natural product containing an indoloquinazoline moiety and has been shown to possess anti-inflammatory and anti-viral activities. Chronic inflammation and hepatitis B are known to be associated with the progression of hepatocellular carcinoma (HCC). In this study, a series of tryptanthrin derivatives were synthesized to generate potent anti-tumor agents against HCC. This effort yielded two compounds, A1 and A6, that exhibited multi-fold higher cytotoxicity in HCC cells than the parent compound. Flow cytometric analysis demonstrated that A1 and A6 caused S-phase arrest and downregulated the expression of cyclin A1, B1, CDK2, and p-CDC2. In addition to inducing caspase-dependent apoptosis, A1 and A6 exhibited similar regulation of the phosphorylation or expression of multiple signaling targets, including Akt, NF-κB, and mitogen-activated protein kinases. The anti-tumor activities of A1 and A6 were also attributable to the generation of reactive oxygen species, accompanied by an increase in p-p53 levels. Therefore, A1 and A6 have potential clinical applications since they target diverse aspects of cancer cell growth in HCC.

SUBMITTER: Gao JY

PROVIDER: S-EPMC8615277 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Novel Ferrocene Derivatives Induce G0/G1 Cell Cycle Arrest and Apoptosis through the Mitochondrial Pathway in Human Hepatocellular Carcinoma.

Project description:In this study, detailed information on hepatocellular carcinoma (HCC) cells (HepG-2, SMMC-7721, and HuH-7) and normal human liver cell L02 treated by ferrocene derivatives (compounds 1, 2 and 3) is provided. The cell viability assay showed that compound 1 presented the most potent and selective anti-HCC activity. Further mechanism study indicated that the proliferation inhibition effect of compound 1 was associated with the cycle arrest at the G0/G1 phase and downregulation of cyclin D1/CDK4. Moreover, compound 1 could induce apoptosis in HCC cells by loss of mitochondrial membrane potential (ΔΨm), accumulation of reactive oxygen species (ROS), decrease in Bcl-2, increase in BAX and Bad, translocation of Cytochrome c, activation of Caspase-9, -3, and cleavage of PARP. These results indicated that compound 1 would be a promising candidate against HCC through G0/G1 cell cycle arrest-related proliferation inhibition and mitochondrial pathway-dependent apoptosis.

| S-EPMC8003055 | biostudies-literature

Moringa peregrina Leaves Extracts Induce Apoptosis and Cell Cycle Arrest of Hepatocellular Carcinoma.

Project description:Moringa grows in the tropical and subtropical regions of the world. The genus Moringa belongs to family Moringaceae. It is found to possess various medicinal uses including hypoglycemic, analgesic, anti-inflammatory, hypolipidemic, and antioxidant activities. In this study, we investigated the antimicrobial and the anticancer activity of the Moringa peregrina as well as Moringa oleifera leaves extracts grown locally in Egypt. Results indicated that most of the extracts were found to possess high antimicrobial activity against gram-positive bacteria, gram-negative bacteria, and fungus. The survival rate of cancer cells was decreased in both hepatocellular carcinoma (HepG2) and breast carcinoma (MCF-7) cell lines when treated with Moringa leaves extracts. In addition, the cell cycle progression, apoptosis, and cancer-related genes confirmed its anticancer effect. The toxicity of each extract was also tested using the normal melanocytes cell line HFB4. The toxicity was low in both Moringa peregrina and Moringa oleifera leaves extracts. Furthermore, GC/MS analysis fractionized the phytochemicals content for each potential extract. In conclusion, results suggested that the Moringa peregrina and Moringa oleifera leaves extracts possess antimicrobial and anticancer properties which could be attributed to the bioactive phytochemical compounds present inside the extracts from this plant. These findings can be used to develop new drugs, especially for liver cancer chemotherapy.

| S-EPMC6332967 | biostudies-literature

Novel Ferrocene Derivatives Induce Apoptosis through Mitochondria-Dependent and Cell Cycle Arrest via PI3K/Akt/mTOR Signaling Pathway in T Cell Acute Lymphoblastic Leukemia.

Project description:T cell acute lymphoblastic leukemia (T-ALL) is one of the most common causes of death in pediatric malignancies. However, the clinical chemotherapy for T-ALL has been limited by numerous side effects, emphasizing that novel anti-T-ALL drugs are urgently needed. Herein, a series of 2-acyl-1-dimethylaminomethyl-ferrocenes for cancer therapy have been evaluated. Among them, F1 and F3 exhibited potent cytotoxicity against T-ALL cell lines, especially Jurkat cells, with low cytotoxicity for normal cells. Further mechanistic studies revealed that F1 and F3 could induce apoptosis in Jurkat cells by destructing mitochondrial membrane, enhancing reactive oxygen species (ROS) generation, decreasing the Bcl-2/Bax ratio, releasing Cytochrome c, and increasing the expression of Cleaved Caspase-9/-3 and Cleaved PARP. Additionally, F1 and F3 could suppress cell proliferation and arrest the cell cycle at G0/G1 phase through the PI3K/Akt/mTOR signaling pathway by down-regulating the expression of CDK6, Cyclin D1, p-Akt, p-GSK-3β, p-mTOR, p-p70 S6K, and up-regulating the expression of P21 and P27, which would also be a possible mechanism. Consequently, ferrocene derivatives F1 and F3 could induce apoptosis through a mitochondria-dependent pathway mediated by ROS, and cell cycle arrest at G0/G1 phase via the PI3K/Akt/mTOR signaling pathway in Jurkat cells. The present study provided fundamental insights into the clinical application of F1 and F3 for the treatment of T-ALL.

| S-EPMC8467123 | biostudies-literature

Synthesis of gypsogenin derivatives with capabilities to arrest cell cycle and induce apoptosis in human cancer cells.

Project description:Thirty-two gypsogenin derivatives were synthesized and screened for their cytotoxic activities. Their structures were established using IR, 1H NMR, 13C NMR, and LC-MS spectroscopic data. In MTT assays nearly all the compounds displayed good cytotoxicity in the low μM range for several human tumour cell lines (A549, LOVO, SKOV3 and HepG2). Low IC50 values were obtained especially for the carboxamides 7a-7j, for an oxime derivative 3 and a (2,4-dinitrophenyl)hydrazono derivative 4. In particular, the IC50 values of compounds 4 (IC50 = 2.97 ± 1.13 µΜ) and 7 g (IC50 = 3.59 ± 2.04 µΜ) against LOVO cells were found to be much lower than those of the other derivatives and parent compound. These compounds were submitted to an extensive biological testing and proved compounds 4 and 7 g to act mainly by an arrest of the tumour cells in the S phase of the cell cycle. In addition, compounds 4 and 7 g triggered the apoptotic pathway in cancer cells, showing high apoptosis ratios.

| S-EPMC5792931 | biostudies-literature

A New Series of Cytotoxic Pyrazoline Derivatives as Potential Anticancer Agents that Induce Cell Cycle Arrest and Apoptosis.

Project description:A new series of pyrazoline derivatives 1b-12b was designed, synthesized and evaluated for antiproliferative activity against three cancer cell lines (HepG-2, Hela and A549). Additionally, NIH/3T3 cell cytotoxicity were tested and the structure activity relationships (SARs) were also determined. Among these new derivatives, the compounds 3-(4-fluorophenyl)-5-(3,4,5-trimethoxythiophenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (1b) and 3-(4-chlorophenyl)-5-(3,4,5-trimethoxythiphenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (2b) showed the best activity against HepG-2 cells, with IC50 values of 6.78 ?M and 16.02 ?M, respectively. They also displayed potent activity against Hela cells; meanwhile, 3-(4-chlorophenyl)-5-(3-bromo-4-hydroxy-5-methoxythiophenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (5b) and 3-(4-bromo-phenyl)-5-(3-bromo-4-hydroxy-5-methoxythiophenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (6b) were also identified as promising anticancer agents against A549 cells owing to their notable inhibitory effect, compared with cisplatin (IC50 = 29.48 ?M). Furthermore, it was also found that compounds 1b and 2b had low cytotoxicity against NIH/3T3 cells and further mechanistic studies revealed that 1b arrested HepG-2 cells cycle at the G2/M phase at high concentrations and induced apoptosis in HepG-2 cells. Moreover, 1b upregulated protein expression level of cleaved caspase-3, cleaved PARP, Bax and p53 and downregulated protein expression level of Bcl-2 in dose-dependent way in HepG-2 cells. Thus, this study indicates that compound 1b might be a promising antitumor drug candidate.

| S-EPMC6151802 | biostudies-literature

Platinum(ii) complexes with rutaecarpine and tryptanthrin derivatives induce apoptosis by inhibiting telomerase activity and disrupting mitochondrial function.

Project description:Four new platinum(ii) complexes, [Pt(Rut)(DMSO)Cl2] (Rut-Pt), [Pt(Try)(DMSO)Cl2] (Try-Pt), [Pt(ITry)(DMSO)Cl2] (ITry-Pt) and [Pt(BrTry)(DMSO)Cl2] (BrTry-Pt), with rutaecarpine (Rut), tryptanthrin (Try), 8-iodine-tryptanthrin (ITry) and 8-bromo-tryptanthrin (BrTry) as ligands were synthesized and fully characterized. In these complexes, the platinum(ii) adopts a four-coordinated square planar geometry. The inhibitory activity evaluated by the MTT assay showed that BrTry-Pt (IC50 = of 0.21 ± 0.25 μM) could inhibit the growth of T-24 tumor cells (human bladder cancer cell line) more so than the other three complexes. In addition, all of these Pt complexes exhibited low toxicity against non-cancerous HL-7702 cells. BrTry-Pt induced cell cycle arrest in the S phase, leading to the down-regulation of cyclin A and CDK2 proteins. BrTry-Pt acts as a telomerase inhibitor targeting the c-myc promoter. In addition, BrTry-Pt also caused mitochondrial dysfunction. Importantly, the in vitro anticancer activity of BrTry-Pt was higher than those of Rut-Pt, Try-Pt and ITry-Pt, and it was more selective for T-24 cells than for non-cancerous HL-7702 cells.

| S-EPMC6195000 | biostudies-literature

Purified brominated indole derivatives from Dicathais orbita induce apoptosis and cell cycle arrest in colorectal cancer cell lines.

Project description:Dicathais orbita is a large Australian marine gastropod known to produce bioactive compounds with anticancer properties. In this research, we used bioassay guided fractionation from the egg mass extract of D. orbita using flash column chromatography and identified fractions containing tyrindoleninone and 6-bromoisatin as the most active against colon cancer cells HT29 and Caco-2. Liquid chromatography coupled with mass spectrometry (LCMS) and 1H NMR were used to characterize the purity and chemical composition of the isolated compounds. An MTT assay was used to determine effects on cell viability. Necrosis and apoptosis induction using caspase/LDH assay and flow cytometry (PI/Annexin-V) and cell cycle analysis were also investigated. Our results show that semi-purified 6-bromoisatin had the highest anti-cancer activity by inhibiting cell viability (IC50 = ~100 µM) and increasing caspase 3/7 activity in both of the cell lines at low concentration. The fraction containing 6-bromoisatin induced 77.6% apoptosis and arrested 25.7% of the cells in G2/M phase of cell cycle in HT29 cells. Tyrindoleninone was less potent but significantly decreased the viability of HT29 cells at IC50 = 390 µM and induced apoptosis at 195 µM by increasing caspase 3/7 activity in these cells. This research will facilitate the development of these molluscan natural products as novel complementary medicines for colorectal cancer.

| S-EPMC3826136 | biostudies-other

Tea pigments induce cell-cycle arrest and apoptosis in HepG2 cells.

Project description:AIM:To investigate the molecular mechanisms by which tea pigments exert preventive effects on liver carcinogenesis. METHODS:HepG2 cells were seeded at a density of 5X10(5)/well in six-well culture dishes and incubated overnight. The cells then were treated with various concentrations of tea pigments over 3 d, harvested by trypsinization, and counted using a hemocytometer. Flow cytometric analysis was performed by a flow cytometer after propidium iodide labeling. Bcl-2 and p21(WAF1) proteins were determined by Western blotting. In addition, DNA laddering assay was performed on treated and untreated cultured HepG2 cells. RESULTS:Tea pigments inhibited the growth of HepG2 cells in a dose-dependent manner. Flow-cytometric analysis showed that tea pigments arrested cell cycle progression at G1 phase. DNA laddering was used to investigate apoptotic cell death, and the result showed that 100 mg/L of tea pigments caused typical DNA laddering. Our study also showed that tea pigments induced upregulation of p21(WAF1) protein and downregulation of Bcl-2 protein. CONCLUSION:Tea pigments induce cell-cycle arrest and apoptosis. Tea pigments may be used as an ideal chemopreventive agent.

| S-EPMC4622794 | biostudies-literature

Fluorinated rhodacyanines induce apoptosis via mitochondrial damage and cell cycle arrest

Project description:Rhodacyanine, a series of cyanines derived from rhodanine, exerts anticancer effects. This study intended to uncover the biological mechanism underlying the anticancer effects of a a fluorinated rhodacyanine in HeLa cervical cancer cells. Initially, the cytotoxic activities of 15 compounds were screened, Rho-7 exhibited the most effective compound against Hela cell growth with IC50 values at 0.03 µM. Interestingly, Rho-7-targeted mitochondrial damage leads to cancer cell death by increasing reactive oxygen species (ROS) levels. Additionally, Rho-7 can trigger Hela cells to undergo apoptosis and cell cycle arrest at the G2/M phase. Rho-7 could downregulate the expression of anti-apoptotic Mcl-1 genes or upregulate the level of pro-apoptotic Bad and Bik genes. Our findings suggest that the anticancer activity of Rho-7 involve ROS generation, cell cycle arrest and apoptotic induction, as well as alteration of pro-and anti-apoptotic genes, displaying a therapeutic potential of Rho-7 in cervical cancer treatment.

2024-01-01 | GSE251969 | GEO

Naphthoquinones from Onosma paniculata induce cell-cycle arrest and apoptosis in melanoma Cells.

Project description:Activity-guided fractionation of a petroleum ether-soluble extract of the roots of Onosma paniculata, which has been shown to affect the cell cycle and to induce apoptosis in melanoma cells, led to the isolation of several shikonin derivatives, namely, ?-hydroxyisovalerylshikonin (1), acetylshikonin (2), dimethylacrylshikonin (3), and a mixture of ?-methylbutyrylshikonin and isovalerylshikonin (4+5). All compounds exhibited strong cytotoxicity against eight cancer cell lines and MRC-5 lung fibroblasts, with 3 found to possess the most potent cytotoxicity toward four melanoma cell lines (SBcl2, WM35, WM9, and WM164). Furthermore, 3 and the mixture of 4+5 were found to interfere with cell-cycle progression in these cell lines and led to an increasing number of cells in the subG1 region as well as to caspase-3/7 activation, indicating apoptotic cell death.

| S-EPMC3361261 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data