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Characterization of novel natural compound derivatives with cancer-selective cytotoxicity

ABSTRACT: Characterization of novel natural compound derivatives with cancer-selective cytotoxicity

PROVIDER: PRJNA647378 | ENA |

REPOSITORIES: ENA

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Characterization of novel natural compound derivatives with cancer-selective cytotoxicity (RNA-seq dataset 2)

Project description:Characterization of novel natural compound derivatives with cancer-selective cytotoxicity (RNA-seq dataset 2)

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Characterization of novel natural compound derivatives with cancer-selective cytotoxicity (RNA-seq dataset 1)

Project description:Characterization of novel natural compound derivatives with cancer-selective cytotoxicity (RNA-seq dataset 1)

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Characterization of novel natural compound derivatives with cancer-selective cytotoxicity (RNA-seq dataset 3)

Project description:Characterization of novel natural compound derivatives with cancer-selective cytotoxicity (RNA-seq dataset 3)

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Characterization of novel natural compound derivatives with cancer-selective cytotoxicity (RNA-seq dataset 1)

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

Characterization of novel natural compound derivatives with cancer-selective cytotoxicity (RNA-seq dataset 3)

2022-03-04 | GSE154754 | GEO

Characterization of novel natural compound derivatives with cancer-selective cytotoxicity (RNA-seq dataset 2)

2022-03-04 | GSE154753 | GEO

Characterization of novel a-Mangostin and Paeonol derivatives with cancer-selective cytotoxicity

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

Selective CDK9 inhibition by natural compound toyocamycin in cancer cell

Project description:Selective CDK9 inhibition by natural compound toyocamycin in cancer cell

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Characterization of novel natural compound derivatives with cancer-selective cytotoxicity

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-03-04 | GSE154755 | GEO

The Golgi stacking protein GRASP55 is targeted by the natural compound prodigiosin

Project description:The bacterial secondary metabolite prodigiosin has been shown to exert anticancer, antimalarial, antibacterial and immunomodulatory properties. With regard to cancer, it has been reported to affect cancer cells but not non-malignant cells, rendering prodigiosin a promising lead compound for anticancer drug discovery. However, a direct protein target has not yet been experimentally identified. Thus, we used mass spectrometry-based thermal proteome profiling and identified the Golgi stacking protein GRASP55 as target protein of prodigiosin. We show that prodigiosin treatment severely affects Golgi morphology and functionality, and that prodigiosin-dependent cytotoxicity is partially reduced in GRASP55 knockout cells. We also found that prodigiosin treatment results in decreased cathepsin activity and overall blocks autophagic flux, whereas co-localization of the autophagosomal marker LC3 and the lysosomal marker LAMP1 is clearly promoted. Finally, we observed that autophagosomes accumulate at GRASP55-positive structures, pointing towards an involvement of an altered Golgi function in the autophagy-inhibitory effect of this natural compound. Taken together, we propose that prodigiosin affects autophagy and Golgi apparatus integrity in an interlinked mode of action involving the regulation of organelle alkalization and the Golgi stacking protein GRASP55.

2023-10-24 | PXD043247 | Pride

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