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<p>Recent findings highlight organotin(IV) compounds as effective anticancer agents, especially for leukemia, offering a potential advancement in cancer therapy by inhibiting cell proliferation with reduced toxicity and resistance issues. Five novel di- and triphenyltin(IV) dithiocarbamate compounds (<b>OC1</b>-<b>OC5</b>) were tested against Jurkat E6.1 human lymphoblastic leukemia cells. All compounds produced potent cytotoxic effects by inducing 55% − 86% of apoptotic events at their respective IC<sub>50</sub> values, 7.1 µM (<b>OC1</b>), 0.1 µM (<b>OC2</b>), 2.8 µM (<b>OC3</b>), 0.2 µM (<b>OC4</b>) and 0.35 µM (<b>OC5</b>). <b>OC2 [Ph</b><sub><b>3</b></sub><b>Sn(</b><Emphasis Type="BoldItalic">N</Emphasis>,<Emphasis Type="BoldItalic">N</Emphasis><b>-diisopropyldithiocarbamate)]</b> was the most potent, with an IC<sub>50</sub> of 0.1 µM and a selectivity index (SI) of 5.5, leading to further investigation. Mechanistic studies revealed that <b>OC2</b> triggers apoptosis in Jurkat cells via the intrinsic pathway by disrupting mitochondrial membranes. This was initiated by DNA damage, leading to excessive reactive oxygen species (ROS) production and activation of caspase cascade (−9, −8, −3). Pretreatment with the antioxidant <i>N</i>-acetyl-L-cysteine (NAC) significantly reduced apoptosis, confirming oxidative stress involvement. <b>OC2</b> also caused G<sub>0</sub>/G<sub>1</sub> cell cycle arrest and upregulated cleaved-PARP and p21. These findings reveal the anti-proliferative ability of <b>OC2</b> in a Jurkat T lymphoblastic leukemia cell model, which warrants further investigation for its antileukemic potential and therapeutic value.</p>

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Mitochondrial apoptosis and G0/G1-phase blockade: key mechanisms underlying triphenyltin(IV) dithiocarbamate-mediated cytotoxicity in human lymphoblastic leukemia cells

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月12日

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  • Sharifah Nadhira Syed Annuar,
  • Nurul Farahana Kamaludin,
  • Normah Awang,
  • Kok Meng Chan

摘要

Recent findings highlight organotin(IV) compounds as effective anticancer agents, especially for leukemia, offering a potential advancement in cancer therapy by inhibiting cell proliferation with reduced toxicity and resistance issues. Five novel di- and triphenyltin(IV) dithiocarbamate compounds (OC1-OC5) were tested against Jurkat E6.1 human lymphoblastic leukemia cells. All compounds produced potent cytotoxic effects by inducing 55% − 86% of apoptotic events at their respective IC50 values, 7.1 µM (OC1), 0.1 µM (OC2), 2.8 µM (OC3), 0.2 µM (OC4) and 0.35 µM (OC5). OC2 [Ph3Sn(N,N-diisopropyldithiocarbamate)] was the most potent, with an IC50 of 0.1 µM and a selectivity index (SI) of 5.5, leading to further investigation. Mechanistic studies revealed that OC2 triggers apoptosis in Jurkat cells via the intrinsic pathway by disrupting mitochondrial membranes. This was initiated by DNA damage, leading to excessive reactive oxygen species (ROS) production and activation of caspase cascade (−9, −8, −3). Pretreatment with the antioxidant N-acetyl-L-cysteine (NAC) significantly reduced apoptosis, confirming oxidative stress involvement. OC2 also caused G0/G1 cell cycle arrest and upregulated cleaved-PARP and p21. These findings reveal the anti-proliferative ability of OC2 in a Jurkat T lymphoblastic leukemia cell model, which warrants further investigation for its antileukemic potential and therapeutic value.