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<p>Lung cancer characterized by its high prevalence and aggressive nature, poses a considerable threat to global health. Recognizing the pressing need for innovative therapeutic strategies, we investigated the synergistic effect and potential mechanisms of nitric oxide-enriched plasma-treated water (NO-PTW) and curcumin in lung cancer treatment. NO-PTW was prepared using a multi-electrode cylindrical dielectric barrier discharge (MC-DBD) plasma system with air-flowing gas. Fibroblasts (MRC-5) and cancerous cells (A549 and H460) were exposed to NO-PTW and curcumin alone and in combination, followed by various analyses. Cytotoxicity assay indicated that curcumin and NO-PTW co-treatment markedly suppressed A549 and H460 cells growth without adversely affecting normal cells. Additionally, there was a marked decline in intracellular adenosine triphosphate levels and a significant increase in dead cells following the combined therapy. Moreover, curcumin and NO-PTW co-treatment increased cell death, membrane permeability, and reactive oxygen and nitrogen species generation. Immunofluorescence staining showed increased γ-H2AX protein expression following the co-therapy, indicating DNA double-strand break in cancer cells. Curcumin and NO-PTW co-treatment significantly upregulated the mRNA expression of key genes associated with DNA damage <i>(ATR</i>,<i> ATM</i>,<i> Chk1</i>,<i> Chk2</i>, and <i>p53)</i> and apoptosis <i>(caspase-3</i>,<i> Bax</i>,<i> PARP</i>, and <i>caspase-8).</i> Mechanistically, curcumin and NO-PTW co-treatment influences cellular processes by stimulating the ATR/ATM/p53 pathway, as evidenced by significant changes in phosphorylation levels. Conclusively, these findings suggest that curcumin and NO-PTW co-treatment induces apoptosis in lung cancer cells, presenting a possible strategy to expanding cancer treatments.</p>

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Investigating the Synergistic Effect of Nitric Oxide Plasma-treated Water and Curcumin on Apoptosis in Lung Cancer Cells via intrinsic and ATR/ATM/p53-Dependent Pathways: An In Vitro Study

  • 期刊论文

  • 发表日期：

    2026年1月3日

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  • Khadija Akter,
  • Jun Sup Lim,
  • Eun Ha Choi

摘要

Lung cancer characterized by its high prevalence and aggressive nature, poses a considerable threat to global health. Recognizing the pressing need for innovative therapeutic strategies, we investigated the synergistic effect and potential mechanisms of nitric oxide-enriched plasma-treated water (NO-PTW) and curcumin in lung cancer treatment. NO-PTW was prepared using a multi-electrode cylindrical dielectric barrier discharge (MC-DBD) plasma system with air-flowing gas. Fibroblasts (MRC-5) and cancerous cells (A549 and H460) were exposed to NO-PTW and curcumin alone and in combination, followed by various analyses. Cytotoxicity assay indicated that curcumin and NO-PTW co-treatment markedly suppressed A549 and H460 cells growth without adversely affecting normal cells. Additionally, there was a marked decline in intracellular adenosine triphosphate levels and a significant increase in dead cells following the combined therapy. Moreover, curcumin and NO-PTW co-treatment increased cell death, membrane permeability, and reactive oxygen and nitrogen species generation. Immunofluorescence staining showed increased γ-H2AX protein expression following the co-therapy, indicating DNA double-strand break in cancer cells. Curcumin and NO-PTW co-treatment significantly upregulated the mRNA expression of key genes associated with DNA damage (ATR, ATM, Chk1, Chk2, and p53) and apoptosis (caspase-3, Bax, PARP, and caspase-8). Mechanistically, curcumin and NO-PTW co-treatment influences cellular processes by stimulating the ATR/ATM/p53 pathway, as evidenced by significant changes in phosphorylation levels. Conclusively, these findings suggest that curcumin and NO-PTW co-treatment induces apoptosis in lung cancer cells, presenting a possible strategy to expanding cancer treatments.