Kudryavtseva, A. | bioRxiv Science

bioRxiv2025

Correlative evaluation of anticancer effects of a modified methioninase MGL-KPV using 2D and 3D cell models, human cancer xenografts in zebrafish embryos and Balb/c nude mice

PurposeThe emergence of new models of tumor growth requires a comparison of the results of the evaluation of the anticancer effect of single drug candidate for the selection of a relevant model. MethodsWe assessed the anticancer activity of the modified enzyme MGL-KPV using four models: 2D cultures, 3D spheroids, zebrafish embryo xenografts, and Balb/c nude mice. Cytotoxicity was tested in cancer cell lines and fibroblasts; efficacy was evaluated in zebrafish and mice. The effect of MGL does not require direct contact with cancer cells, making it unique drug candidate for in vitro and in vivo comparison. ResultsMGL-KPV showed selective cytotoxicity with IC50 values of 0.23-2.21 U/mL (2D) and 1.43-4.82 U/mL (3D), sparing fibroblasts. HCT-116 and Panc-1 were most sensitive. In zebrafish xenografts, tumor size reduced by 70% (HCT-116) and 43% (Panc-1); in mice -- by 45% and 34%, respectively. ConclusionsMGL-KPV demonstrated significant anticancer activity across all models. These results support step-by-step non-clinical proof-of-concept studies approach for amino-acid cleaving enzymes with anticancer properties.

pharmacology and toxicology↗

bioRxiv2019

Gray whale transcriptome reveals longevity adaptations associated with DNA repair, autophagy and ubiquitination

One important question in aging research is how differences in genomics and transcriptomics determine the maximum lifespan in various species. Despite recent progress, much is still unclear on the topic, partly due to the lack of samples in non-model organisms and due to challenges in direct comparisons of transcriptomes from different species. The novel ranking-based method that we employ here is used to analyze gene expression in the gray whale and compare its de novo assembled transcriptome with that of other long- and short-lived mammals. Gray whales are among the top 1% longest-lived mammals. Despite the extreme environment, or maybe due to a remarkable adaptation to its habitat (intermittent hypoxia, Arctic water, and high pressure), gray whales reach at least the age of 77 years. In this work, we show that long-lived mammals share common gene expression patterns between themselves, including high expression of DNA maintenance and repair, ubiquitination, apoptosis, and immune responses. Additionally, the level of expression for gray whale orthologs of pro- and anti-longevity genes found in model organisms is in support of their alleged role and direction in lifespan determination. Remarkably, among highly expressed pro-longevity genes many are stress-related, reflecting an adaptation to extreme environmental conditions. The conducted analysis suggests that the gray whale potentially possesses high resistance to cancer and stress, at least in part ensuring its longevity. This new transcriptome assembly also provides important resources to support the efforts of maintaining the endangered population of gray whales.

evolutionary biology↗