A New Hybrid δ-Lactone Induces Apoptosis and Potentiates Anticancer Activity of Taxol in HL-60 Human Leukemia Cells

Gach-Janczak, Katarzyna; Drogosz-Stachowicz, Joanna; Długosz-Pokorska, Angelika; Jakubowski, Rafał; Janecki, Tomasz; Szymański, Jacek; Janecka, Anna

doi:10.3390/molecules25071479

Cited by 4 publications

(2 citation statements)

References 60 publications

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“…The second substructure (Figure B) is the lactone structure. Several compounds containing lactone exhibited remarkable in vitro cytotoxic activity as well as apoptosis against non-small cell lung, breast, and leukemia cancer cell lines. , …”

Section: Resultsmentioning

confidence: 99%

pdCSM-cancer: Using Graph-Based Signatures to Identify Small Molecules with Anticancer Properties

Al‐Jarf

Sá

Pires

et al. 2021

J. Chem. Inf. Model.

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The development of new, effective, and safe drugs to treat cancer remains a challenging and time-consuming task due to limited hit rates, restraining subsequent development efforts. Despite the impressive progress of quantitative structure–activity relationship and machine learning-based models that have been developed to predict molecule pharmacodynamics and bioactivity, they have had mixed success at identifying compounds with anticancer properties against multiple cell lines. Here, we have developed a novel predictive tool, pdCSM-cancer, which uses a graph-based signature representation of the chemical structure of a small molecule in order to accurately predict molecules likely to be active against one or multiple cancer cell lines. pdCSM-cancer represents the most comprehensive anticancer bioactivity prediction platform developed till date, comprising trained and validated models on experimental data of the growth inhibition concentration (GI50%) effects, including over 18,000 compounds, on 9 tumor types and 74 distinct cancer cell lines. Across 10-fold cross-validation, it achieved Pearson’s correlation coefficients of up to 0.74 and comparable performance of up to 0.67 across independent, non-redundant blind tests. Leveraging the insights from these cell line-specific models, we developed a generic predictive model to identify molecules active in at least 60 cell lines. Our final model achieved an area under the receiver operating characteristic curve (AUC) of up to 0.94 on 10-fold cross-validation and up to 0.94 on independent non-redundant blind tests, outperforming alternative approaches. We believe that our predictive tool will provide a valuable resource to optimizing and enriching screening libraries for the identification of effective and safe anticancer molecules. To provide a simple and integrated platform to rapidly screen for potential biologically active molecules with favorable anticancer properties, we made pdCSM-cancer freely available online at .

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Section: Resultsmentioning

confidence: 99%

pdCSM-cancer: Using Graph-Based Signatures to Identify Small Molecules with Anticancer Properties

Al‐Jarf

Sá

Pires

et al. 2021

J. Chem. Inf. Model.

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“…Apoptosis was detected by Tunnel assay using the APO-DIRECT™ Kit [31] (Catalog no. 6536KK, BD Biosciences Pharmingen).…”

Section: Tunel Assay For Detection Of Apoptosismentioning

confidence: 99%

JC-10 probe as a novel method for analyzing the mitochondrial membrane potential and cell stress in whole zebrafish embryos

Younes

Alsahan

Al-Mesaifri

et al. 2021

Toxicology Research

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Background A sensitive method to investigate cellular stress and cytotoxicity is based on measuring mitochondrial membrane potential. Recently, JC-10, was developed to measure mitochondrial membrane potential in vitro and used as an indicator for cytotoxicity. Yet, JC-10 has never been used in vivo (whole organism). In normal cells, JC-10 concentrates in the mitochondrial matrix, where it forms red fluorescent aggregates. However, in apoptotic/necrotic cells, JC-10 diffuses out of the mitochondria, changes to monomeric form, and stains cells in green. Here, we aimed to develop and optimize a JC-10 assay to measure cytotoxicity in zebrafish embryo. We also investigated the effectiveness of JC-10 assay by comparing it to common cytotoxicity assays. Methods Zebrafish embryos were exposed to a toxic surfactant AEO-7 at no observed effect concentration (6.4 μg/L), and then cytotoxicity was measured using (i) JC-10 mitochondrial assay, (ii) acridine orange (AO), (iii) TUNEL assay, and (iv) measuring the level of Hsp70 by western blotting. Results As compared to the negative control, embryos treated with NOEC of AEO-7 did not show significant cytotoxicity when assessed by AO, TUNEL or western blotting. However, when JC-10 was used under the same experimental conditions, a significant increase of green:red fluorescent ratio signal was detected in the AEO-7 treated embryos, indicating mitochondrial damage and cellular cytotoxicity. Noteworthy, the observed green: red ratio increase was dose dependent, suggesting specificity of the JC-10 assay. Conclusion JC-10 is a sensitive in vivo method, thus, can be used as surrogate assay to measure cytotoxicity in whole zebrafish embryos.

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Programmed cell death, redox imbalance, and cancer therapeutics

2021

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A New Hybrid δ-Lactone Induces Apoptosis and Potentiates Anticancer Activity of Taxol in HL-60 Human Leukemia Cells

Cited by 4 publications

References 60 publications

pdCSM-cancer: Using Graph-Based Signatures to Identify Small Molecules with Anticancer Properties

pdCSM-cancer: Using Graph-Based Signatures to Identify Small Molecules with Anticancer Properties

JC-10 probe as a novel method for analyzing the mitochondrial membrane potential and cell stress in whole zebrafish embryos

Programmed cell death, redox imbalance, and cancer therapeutics

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