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<p>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.</p>

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Enhanced Anti-Leukemic Activity of Platinum Lamivudine Compared To Lamivudine Through Differential Gene Regulation and DNA Groove Binding

  • 期刊论文

  • 发表日期：

    2025年8月8日

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  • Asal Shahmohammadi,
  • Abdolreza Sabokrouh,
  • Farrokh Modarresi

摘要

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.