2026-09-14T13:29:19Zhttps://gredos.usal.es/oai/request

oai:gredos.usal.es:10366/1669682025-09-10T00:02:11Zcom_10366_149436com_10366_3947com_10366_3946com_10366_3823col_10366_151253

Hernández, Ángela-Patricia Chaparro-González, Lorea Garzo-Sánchez, Olga Arias-Hidalgo, Carlota Juanes-Velasco, Pablo García, Pablo A. Castro, Mª Ángeles Fuentes, Manuel 2025-09-09T08:09:44Z 2025-09-09T08:09:44Z 2024 http://hdl.handle.net/10366/166968 10.3390/ijms25094631 1422-0067 When new antitumor therapy drugs are discovered, it is essential to address new target molecules from the point of view of chemical structure and to carry out efficient and systematic evaluation. In the case of natural products and derived compounds, it is of special importance to investigate chemomodulation to further explore antitumoral pharmacological activities. In this work, the compound podophyllic aldehyde, a cyclolignan derived from the chemomodulation of the natural product podophyllotoxin, has been evaluated for its viability, influence on the cell cycle, and effects on intracellular signaling. We used functional proteomics characterization for the evaluation. Compared with the FDA-approved drug etoposide (another podophyllotoxin derivative), we found interesting results regarding the cytotoxicity of podophyllic aldehyde. In addition, we were able to observe the effect of mitotic arrest in the treated cells. The use of podophyllic aldehyde resulted in increased cytotoxicity in solid tumor cell lines, compared to etoposide, and blocked the cycle more successfully than etoposide. High-throughput analysis of the deregulated proteins revealed a selective antimitotic mechanism of action of podophyllic aldehyde in the HT-29 cell line, in contrast with other solid and hematological tumor lines. Also, the apoptotic profile of podophyllic aldehyde was deciphered. The cell death mechanism is activated independently of the cell cycle profile. The results of these targeted analyses have also shown a significant response to the signaling of kinases, key proteins involved in signaling cascades for cell proliferation or metastasis. Thanks to this comprehensive analysis of podophyllic aldehyde, remarkable cytotoxic, antimitotic, and other antitumoral features have been discovered that will repurpose this compound for further chemical transformations and antitumoral analysis. eng http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess Attribution-NonCommercial-NoDerivatives 4.0 Internacional natural products; podophyllic aldehyde; podophyllotoxin; etoposide; functional proteomics; antibody microarray; cell cycle; high-throughput screening Podophyllic Aldehyde, a Podophyllotoxin Derivate, Elicits Different Cell Cycle Profiles Depending on the Tumor Cell Line: A Systematic Proteomic Analysis info:eu-repo/semantics/article