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<p>Cervical cancer continues to be a predominant cause of cancer-related mortality among women worldwide, particularly in developing countries. Although several standard therapeutic options are currently available for cervical cancer, their associated limitations, including toxicity, resistance, and limited selectivity, necessitate the development of safer and more effective alternative agents. Hence. the present study aimed to green-synthesize zinc oxide nanoparticles (ZnONPs) using the aqueous leaf extract of <i>Piper betle</i> and to evaluate their anticancer efficacy and intrinsic apoptotic mechanisms in cervical cancer cells. In this study, we report the green synthesis of zinc oxide nanoparticles (ZnONPs) using the aqueous leaf extract of <i>Piper betle</i>, a novel approach that leverages the bioactive properties of the plant for nanoparticle fabrication. This study investigated the green synthesis of zinc oxide nanoparticles (ZnONPs) using the aqueous leaf extract of <i>Piper betle</i> and assessed their anticancer efficacy against HeLa cells. The synthesized <i>Piper betle</i>-mediated ZnONPs (PB-ZnONPs) were characterized using UV-Vis, FTIR, DLS, XRD, SEM, and TEM analysis, confirming their nanoscale dimensions, crystallinity, and surface features. Cytotoxicity assay revealed that PB-ZnONPs decreased HeLa cell viability in a dose-dependent manner, with an IC₅₀ of 60&#xa0;µg/mL. In contrast, PB-ZnONPs exhibited no significant toxicity to L929 cells, with an IC<sub>50</sub> exceeding 90&#xa0;µg/mL. Apoptosis induction was examined using AO/EtBr and Hoechst 33,342 nuclear staining, and increased ROS levels were assessed using DCFH-DA. PB-ZnONPs markedly inhibited cell migration, as evidenced by the scratch assay, and induced cell cycle arrest in the G2/M and S phases of the cell cycle. qRT-PCR analysis demonstrated the upregulation of pro-apoptotic genes, such as <i>bax</i>, <i>cas-3</i>, and <i>cas-9</i>, with the downregulation of the anti-apoptotic gene <i>bcl-2</i>, indicating the activation of the intrinsic apoptotic pathway. These findings underscore the potential of PB-ZnONPs as a promising green-synthesized nanotherapeutic agent for cervical cancer treatment.</p>

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Piper Betle Derived Zinc Oxide Nanoparticles Induce Cervical Cancer Cell Apoptosis Via the ROS-mediated Mitochondrial Bax/Bcl-2–Caspase Signaling Axis

  • 期刊论文

  • 发表日期：

    2026年3月3日

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  • Arul Narayanasamy,
  • Nandita Ravichandran,
  • Deenathayalan Uvarajan,
  • Asmatanzeem Bepari,
  • Yomna Khaled,
  • Shaik Kalimulla Niazi,
  • Paulpandi Manickam,
  • Ramya Sennimalai

摘要

Cervical cancer continues to be a predominant cause of cancer-related mortality among women worldwide, particularly in developing countries. Although several standard therapeutic options are currently available for cervical cancer, their associated limitations, including toxicity, resistance, and limited selectivity, necessitate the development of safer and more effective alternative agents. Hence. the present study aimed to green-synthesize zinc oxide nanoparticles (ZnONPs) using the aqueous leaf extract of Piper betle and to evaluate their anticancer efficacy and intrinsic apoptotic mechanisms in cervical cancer cells. In this study, we report the green synthesis of zinc oxide nanoparticles (ZnONPs) using the aqueous leaf extract of Piper betle, a novel approach that leverages the bioactive properties of the plant for nanoparticle fabrication. This study investigated the green synthesis of zinc oxide nanoparticles (ZnONPs) using the aqueous leaf extract of Piper betle and assessed their anticancer efficacy against HeLa cells. The synthesized Piper betle-mediated ZnONPs (PB-ZnONPs) were characterized using UV-Vis, FTIR, DLS, XRD, SEM, and TEM analysis, confirming their nanoscale dimensions, crystallinity, and surface features. Cytotoxicity assay revealed that PB-ZnONPs decreased HeLa cell viability in a dose-dependent manner, with an IC₅₀ of 60 µg/mL. In contrast, PB-ZnONPs exhibited no significant toxicity to L929 cells, with an IC50 exceeding 90 µg/mL. Apoptosis induction was examined using AO/EtBr and Hoechst 33,342 nuclear staining, and increased ROS levels were assessed using DCFH-DA. PB-ZnONPs markedly inhibited cell migration, as evidenced by the scratch assay, and induced cell cycle arrest in the G2/M and S phases of the cell cycle. qRT-PCR analysis demonstrated the upregulation of pro-apoptotic genes, such as bax, cas-3, and cas-9, with the downregulation of the anti-apoptotic gene bcl-2, indicating the activation of the intrinsic apoptotic pathway. These findings underscore the potential of PB-ZnONPs as a promising green-synthesized nanotherapeutic agent for cervical cancer treatment.