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<p>Gastric carcinoma remains a major cause of cancer-related mortality worldwide, underscoring the need for alternative therapeutic strategies. Zinc oxide nanoparticles (ZnO NPs) have attracted attention in cancer research due to their ability to generate reactive oxygen species (ROS), relative cost-effectiveness, and suitability for green synthesis approaches. In this study, ZnO NPs were synthesized via an eco-friendly biogenic method using <i>Artemisia sieberi</i>, and their anticancer-related effects were evaluated in vitro. ZnO nanoparticles were synthesized using an aqueous extract of <i>Artemisia sieberi</i> and characterized by FE-SEM, DLS, EDS, and XRD. Their biological effects were investigated in human gastric adenocarcinoma (AGS) cells and normal human embryonic kidney (HEK-293) cells. Cytotoxicity was assessed using the MTT assay, apoptosis by flow cytometry, cell migration by a wound healing assay, and gene expression by qRT-PCR. Statistical analysis was performed using one-way ANOVA, with <i>p</i> &lt; 0.05 considered significant. Physicochemical characterization confirmed the formation of spherical to polyhedral ZnO nanoparticles with sizes ranging from 37 to 122&#xa0;nm. The nanoparticles exhibited concentration-dependent cytotoxicity in AGS cells, with an IC₅₀ of approximately 480&#xa0;µg/mL, compared to an IC₅₀ of approximately 1250&#xa0;µg/mL in HEK-293 cells, corresponding to a modest selectivity index (~ 2.6). Flow cytometric analysis demonstrated increased apoptosis in AGS cells, with up to 61.6% apoptotic cells observed at the highest concentration. In addition, ZnO NPs significantly inhibited cancer cell migration. Molecular analysis revealed significant upregulation of <i>p53</i>, <i>Caspase-9</i>, and <i>Caspase-3</i>, suggesting activation of the intrinsic mitochondrial apoptotic pathway. The findings indicate that <i>Artemisia sieberi</i>-derived ZnO nanoparticles can induce apoptosis and inhibit migration in gastric cancer cells in vitro, potentially through a p53-mediated mitochondrial mechanism. Although the observed selectivity toward cancer cells was limited, these results support the preliminary potential of biogenically synthesized ZnO nanoparticles as candidates for further investigation. Additional studies, including in vivo models and broader mechanistic analyses, are required to clarify their therapeutic relevance.</p>

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A novel therapeutic strategy against gastric carcinoma: artemisia sieberi-derived biogenic zno nanoparticles inducing intrinsic apoptosis and suppressing AGS cell proliferation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月19日

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  • Nilofar Akbarzadeh,
  • Mohammadreza Pourmohammad,
  • Homa Mahmoudzadeh,
  • Maryam Tehranipour

摘要

Gastric carcinoma remains a major cause of cancer-related mortality worldwide, underscoring the need for alternative therapeutic strategies. Zinc oxide nanoparticles (ZnO NPs) have attracted attention in cancer research due to their ability to generate reactive oxygen species (ROS), relative cost-effectiveness, and suitability for green synthesis approaches. In this study, ZnO NPs were synthesized via an eco-friendly biogenic method using Artemisia sieberi, and their anticancer-related effects were evaluated in vitro. ZnO nanoparticles were synthesized using an aqueous extract of Artemisia sieberi and characterized by FE-SEM, DLS, EDS, and XRD. Their biological effects were investigated in human gastric adenocarcinoma (AGS) cells and normal human embryonic kidney (HEK-293) cells. Cytotoxicity was assessed using the MTT assay, apoptosis by flow cytometry, cell migration by a wound healing assay, and gene expression by qRT-PCR. Statistical analysis was performed using one-way ANOVA, with p < 0.05 considered significant. Physicochemical characterization confirmed the formation of spherical to polyhedral ZnO nanoparticles with sizes ranging from 37 to 122 nm. The nanoparticles exhibited concentration-dependent cytotoxicity in AGS cells, with an IC₅₀ of approximately 480 µg/mL, compared to an IC₅₀ of approximately 1250 µg/mL in HEK-293 cells, corresponding to a modest selectivity index (~ 2.6). Flow cytometric analysis demonstrated increased apoptosis in AGS cells, with up to 61.6% apoptotic cells observed at the highest concentration. In addition, ZnO NPs significantly inhibited cancer cell migration. Molecular analysis revealed significant upregulation of p53, Caspase-9, and Caspase-3, suggesting activation of the intrinsic mitochondrial apoptotic pathway. The findings indicate that Artemisia sieberi-derived ZnO nanoparticles can induce apoptosis and inhibit migration in gastric cancer cells in vitro, potentially through a p53-mediated mitochondrial mechanism. Although the observed selectivity toward cancer cells was limited, these results support the preliminary potential of biogenically synthesized ZnO nanoparticles as candidates for further investigation. Additional studies, including in vivo models and broader mechanistic analyses, are required to clarify their therapeutic relevance.