Majusculamide-o, a Simplified Marine Natural Product Analog, Exhibits Potent and Specific Cancer Cell Cytotoxicity
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PROVIDER: PRJNA1304560 | ENA |
REPOSITORIES: ENA
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Project description:To investigate how a natural product analog mitigates AD, cortical transcriptomes from WT and 5xFAD mice were analyzed. Comparing vehicle-treated groups revealed extensive differential expression associated with neuroinflammation in 5xFAD mice. This was attenuated in the 5xFAD mice treated with the natural product, whose profiles resembled WT controls. RNA seq suggested the natural product regulated the nervous and immune systems.
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Project description:Cigarette smoke causes diseases such as cardiovascular disorders. Heating tobacco, instead of burning, reduces consistently the amount of toxic compounds and may exert a reduced impact on cardiovascular health compared to cigarettes. Aqueous extract from the aerosol of a potential modified risk tobacco product, the carbon-heated tobacco product (CHTP) 1.2 was assessed in vitro for its impact, compared with a reference cigarette (3R4F), on a key mechanism of atherosclerosis, the adhesion of monocytic cells to artery endothelial cells. Human coronary arterial endothelial cells (HCAECs) were treated for 4h with conditioned media from monocytic Mono Mac-6 (MM6) cells exposed to the aqueous aerosol/smoke extracts for 2h (Indirect exposure) or directly with those extracts freshly generated (Fresh Direct exposure). Using a previously established in vitro adhesion assay design, MM6-HCAEC adhesion combined with inflammatory, oxidative stress, cytotoxicity and cell death markers was measured. The 3R4F extract promoted the adhesion of MM6 cells to HCAECs via distinct inflammatory- and cytotoxicity-driven mechanisms. In conclusions, our systems toxicology study demonstrated that approximately 10-15-fold higher concentrations of the CHTP1.2 aerosol extract were needed to elicit similar effects as the 3R4F smoke extract on cardiovascular disease-relevant inflammation and cytotoxicity-related mechanisms and markers investigated in vitro.
2018-08-09 | E-MTAB-6721 | biostudies-arrayexpress
Project description:In our continuing study of the desmosdumotin C (1) series, twelve new analogues, 21–32, mainly with A-ring modifications, were prepared and evaluated for in vitro anticancer activity against several human tumor cell lines. Among them, the 4?-iodo-3,3,5-tripropyl-4-methoxy analogue (31) showed significant cytotoxicity against multiple human tumor cell lines with ED50 values of 1.1–2.8 microM. Elongation of the C-3 and C-5 carbon chains reduced activity relative to propyl substituted analogues; however, activity was still better than that of natural 1. Among analogues with various ether groups on C-4, compounds with methyl (2) and propyl (26) ethers inhibited cell growth of multiple tumor cells lines, while 28 with an iso-butyl ether showed selective cytotoxicity against lung cancer A549 cells (ED50 1.7 microM). The gene expression profiles showed that 3 may modulate the spindle assembly checkpoint (SAC) and chromosome separation, and thus, arrest cells at the G2/M-phase. We used microarrays to elucidate the underlying antitumor mechanism induced by Desmosdumotin C Analog Analogue 3 showed potent cytotoxicity against the highly invasive non-small-cell lung cancer cell line CL1-5 with an ED50 value of 0.11 µM. To determine which genes were differentially expressed upon CL1-5 treatment with analogue 3, the genome-wide mRNA expression profiles of 3-treated cells and control cells were determined using Affymetrix human genome U133 plus 2.0 GeneChip according to the Manufacturer’s protocols
2011-01-03 | E-GEOD-24584 | biostudies-arrayexpress
Project description:Submerged Analog Environment Raw sequence reads
| PRJNA559397 | ENA
Project description:In our continuing study of the desmosdumotin C (1) series, twelve new analogues, 21–32, mainly with A-ring modifications, were prepared and evaluated for in vitro anticancer activity against several human tumor cell lines. Among them, the 4′-iodo-3,3,5-tripropyl-4-methoxy analogue (31) showed significant cytotoxicity against multiple human tumor cell lines with ED50 values of 1.1–2.8 microM. Elongation of the C-3 and C-5 carbon chains reduced activity relative to propyl substituted analogues; however, activity was still better than that of natural 1. Among analogues with various ether groups on C-4, compounds with methyl (2) and propyl (26) ethers inhibited cell growth of multiple tumor cells lines, while 28 with an iso-butyl ether showed selective cytotoxicity against lung cancer A549 cells (ED50 1.7 microM). The gene expression profiles showed that 3 may modulate the spindle assembly checkpoint (SAC) and chromosome separation, and thus, arrest cells at the G2/M-phase. We used microarrays to elucidate the underlying antitumor mechanism induced by Desmosdumotin C Analog
2011-01-03 | GSE24584 | GEO
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2021-11-02 | PXD029315 | Pride