Similar Datasets
Project description:Colorectal cancer is one of the most frequent and lethal cancer in the world. Current therapeutic approaches are still not fully successful, yet cause numerous and severe side effects for the patient. We screened chemically synthesized derivatives from two natural compounds (a-Mangostin and Paeonol) as potential novel chemicals that increase cancer cell selectivity over non-transformed human cells. We found two of them that efficiently induced cell cycle arrest and apoptosis in human cancer cells and organoids derived from tumor tissue without affecting the viability of human non-cancer cells and intestinal organoids derived from healthy tissue. Our findings increase the knowledge about cancer-specific compounds and propose two natural compound derivatives as potential novel chemotherapeutics.
2022-03-04 | GSE154753 | GEO
Project description:Colorectal cancer is one of the most frequent and lethal cancer in the world. Current therapeutic approaches are still not fully successful, yet cause numerous and severe side effects for the patient. We screened chemically synthesized derivatives from two natural compounds (a-Mangostin and Paeonol) as potential novel chemicals that increase cancer cell selectivity over non-transformed human cells. We found two of them that efficiently induced cell cycle arrest and apoptosis in human cancer cells and organoids derived from tumor tissue without affecting the viability of human non-cancer cells and intestinal organoids derived from healthy tissue. Our findings increase the knowledge about cancer-specific compounds and propose two natural compound derivatives as potential novel chemotherapeutics.
2022-03-04 | GSE154754 | GEO
Project description:Colorectal cancer is one of the most frequent and lethal cancer in the world. Current therapeutic approaches are still not fully successful, yet cause numerous and severe side effects for the patient. We screened chemically synthesized derivatives from two natural compounds (a-Mangostin and Paeonol) as potential novel chemicals that increase cancer cell selectivity over non-transformed human cells. We found two of them that efficiently induced cell cycle arrest and apoptosis in human cancer cells and organoids derived from tumor tissue without affecting the viability of human non-cancer cells and intestinal organoids derived from healthy tissue. Our findings increase the knowledge about cancer-specific compounds and propose two natural compound derivatives as potential novel chemotherapeutics.
2022-03-04 | GSE154752 | GEO
Project description:Characterization of novel natural compound derivatives with cancer-selective cytotoxicity
| PRJNA647378 | ENA
Project description:Characterization of novel natural compound derivatives with cancer-selective cytotoxicity (RNA-seq dataset 3)
| PRJNA647381 | ENA
Project description:Characterization of novel natural compound derivatives with cancer-selective cytotoxicity (RNA-seq dataset 2)
| PRJNA647379 | ENA
Project description:Characterization of novel natural compound derivatives with cancer-selective cytotoxicity (RNA-seq dataset 1)
| PRJNA647380 | ENA
Project description:a-Mangostin and Paeonol have shown anti-cancer and anti-inflammatory properties, however these two natural compounds have no clinical value because of their low solubility and low membrane permeability. In this study, we screened chemically synthesized derivatives from these two natural compounds as potential novel chemicals that increase cancer cell cytotoxicity over non-transformed human cells. We found the two derivative compounds, named a-Mangostin-1 (aMan1) and Paeonol-1 (Pae1) more efficiently and specifically induced cytotoxicity in HCT116, HT-29, and SW48 colorectal cancer cell lines than the parental compounds. Both, aMan1 and Pae1 arrested HCT116 cells in G1 and HT-29 and SW48 cells in G2/M phase of the cell cycle. Both aMan1 and Pae1 induced apoptosis in human cancer cells, through a Caspase-dependent mechanism. aMan1 and Pae1 induced selective transcriptional responses in CRC cells involving genes related to metabolic stress and DNA damage response signaling pathways. Finally, experiments on primary colon organoids showed that both the novel derivatives kill organoids derived from cancer without affecting the viability of organoids derived from healthy tissue, where the parental compounds and the currently-used chemotherapeutic drug Irinotecan failed in. In conclusion, our findings increase the knowledge about natural compound derivatives as anticancer compounds and open new research options on the derivation of lead compounds aimed to the development of novel CRC chemotherapeutic drugs that selectively target cancer, but not healthy cells.
2023-03-11 | PXD024999 | Pride
Project description:Aberrant transcription in cancer cells is characterized by silencing of tumor suppressor genes (TSG) and activation of oncogenes. Transcriptomic changes are associated with epigenomic alterations such as DNA hypermethylation, histone deacetylation, and chromatin condensation in promoter regions of silenced TSG. To discover novel drugs that trigger tumor suppressor genes reactivation in cancer cells, we used a GFP reporter system whose expression is silenced by promoter DNA hypermethyation and histone deacetylation. After screening a natural product drug library, we identified toyocamycin, an adenosine analog that induced potent GFP reactivation and loss of clonogenicity in human colon cancer cells. Toyocamycin induced a downregulation in gene pathways involved in RNA pol II transcription regulation. Connectivity mapping analysis revealed that toyocamycin produced a pharmacological signature mimicking cyclin-dependent kinase (CDK) inhibitors. Using RNA-sequencing, we showed that toyocamycin transcriptomic signature closely resembled the profile of a specific CDK9 inhibitor (HH1). Specific inhibition of RNA pol II phosphorylation level and enzymatic kinase assays confirmed that toyocamycin inhibits specifically CDK9 (IC50 = 79nM) with a greater efficacy than other CDKs (IC50 values between 0.67-15µM). Molecular docking showed that toyocamycin binds efficiently CDK9 catalytic site with a different pose than in other CDKs, which was explained by the binding contribution of specific amino acids within the catalytic pocket and the backbone of the protein. Altogether, we demonstrated that toyocamycin exhibits specific CDK9 inhibition in cancer cells, highlighting its potential for cancer chemotherapy.
2022-05-14 | GSE202744 | GEO
Project description:Aberrant transcription in cancer cells involves the silencing of tumor suppressor genes (TSGs) and activation of oncogenes. Transcriptomic changes are associated with epigenomic alterations such as DNA-hypermethylation, histone deacetylation, and chromatin condensation in promoter regions of silenced TSGs. To discover novel drugs that trigger TSG reactivation in cancer cells, we used a GFP-reporter system whose expression is silenced by promoter DNA hypermethylation and histone deacetylation. After screening a natural product drug library, we identified that toyocamycin, an adenosine-analog, induces potent GFP reactivation and loss of clonogenicity in human colon cancer cells. Connectivity-mapping analysis revealed that toyocamycin produces a pharmacological signature mimicking cyclin-dependent kinase (CDK) inhibitors. RNA-sequencing revealed that the toyocamycin transcriptomic signature resembles that of a specific CDK9 inhibitor (HH1). Specific inhibition of RNA Pol II phosphorylation level and kinase assays confirmed that toyocamycin specifically inhibits CDK9 (IC50 = 79 nM) with a greater efficacy than other CDKs (IC50 values between 0.67 and 15 µM). Molecular docking showed that toyocamycin efficiently binds the CDK9 catalytic site in a conformation that differs from other CDKs, explained by the binding contribution of specific amino acids within the catalytic pocket and protein backbone. Altogether, we demonstrated that toyocamycin exhibits specific CDK9 inhibition in cancer cells, highlighting its potential for cancer chemotherapy.
| S-EPMC9324262 | biostudies-literature