ArticleCell biochemistry and biophysics2025
Enhanced Anti-Leukemic Activity of Platinum Lamivudine Compared To Lamivudine Through Differential Gene Regulation and DNA Groove Binding.
Article in Cell biochemistry and biophysics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Acute lymphoblastic leukemia remains a significant therapeutic challenge, necessitating the development of more effective treatments. This study investigates the comparative effects of Pt-Lam and Lam on gene expression biomarkers in human ALL cells. Four experimental groups were analyzed: control (Group A), untreated ALL cells (Group B), Pt-Lam-treated cells (Group C), and Lam-treated cells (Group D). IC₅₀ values were determined using the MTT assay, followed by RNA extraction, cDNA synthesis, and qPCR analysis. Viscosity measurements and UV-visible spectroscopy were employed to assess drug interactions with lymphoblastic DNA. Pt-Lam significantly upregulated pro-apoptotic genes except miRNA-122, including FASLG (2.16 ± 0.62), BAX (2.25 ± 0.21), and miRNA-122 (0.39 ± 0.12), compared to Lam-treated cells: FASLG (1.13 ± 0.06), BAX (1.12 ± 0.11), and miRNA-122 (0.91 ± 0.19). Conversely, anti-apoptotic gene expression was markedly lower in the Pt-Lam group: telomerase (0.53 ± 0.15), Bcl-2 (0.47 ± 0.10), and miRNA-21 (0.30 ± 0.12), compared to Lam-treated cells: telomerase (0.82 ± 0.15), Bcl-2 (0.93 ± 0.21), and miRNA-21 (0.83 ± 0.22), miRNA-122, was found to be upregulated in the untreated group.Viscosity measurements and UV-visible spectroscopy confirmed that Pt-Lam and Lam interact with ALL DNA, exhibiting DNA binding and hypochromic effects indicative of groove binding. Hyperactivation of tyrosine kinase receptors and the PI3K/Akt/mTOR pathway appears to play a significant role in ALL progression. Pt-Lam induces stronger DNA damage and apoptosis than Lam by selectively binding GC-rich DNA grooves, suggesting its potential as a safer, more effective ALL treatment.
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