Abstract The interactions of nanomaterials with biological materials such as immortalized cell lines are recently on the rise. Owing to this superiority, the biosynthesis of AgNPs using gallic acid as a reductant was implemented in this study. After being synthesized, the AgNPs were characterized using techniques such as dynamic light scattering, transmission electron microscopy, selected area electron diffraction, and X-ray diffraction methods. Furthermore, the AgNPs were assessed for their cytotoxic effects on the colorectal adenocarcinoma cell line HT-29. The mechanisms of such cell-killing effect were investigated by analyzing the expressions of 14 mRNAs using quantitative polymerase chain reaction. The outcomes indicate that the synthesized AgNPs were cytotoxic on HT-29 cells. The expressions of all apoptotic genes analyzed including cyt-C, p53, Bax, Bcl2, CASP3, CASP8, CASP9, and CASP12 were upregulated. With regard to the autophagy-related genes, Beclin-1, XBP-1, CHOP, and LC3-II were upregulated, whereas the expressions of ATG3 and ATG12 were downregulated. To conclude, the AgNPs induced mitochondria-dependent apoptosis and non-canonical autophagy in HT-29 cells. A crosstalk did occur between autophagy and apoptosis in such a cell-killing effect. Hence, further studies are required to elucidate the exact mechanisms in animal models for further use of AgNPs in clinical medicine for the treatment of neoplasms of the digestive tract.

中文翻译：

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银纳米粒子在 HT-29 结肠癌细胞中诱导线粒体依赖性细胞凋亡和晚期非典型自噬

摘要 纳米材料与永生化细胞系等生物材料的相互作用最近呈上升趋势。由于这种优势，本研究实施了以没食子酸为还原剂的 AgNPs 的生物合成。合成后，使用动态光散射、透射电子显微镜、选区电子衍射和 X 射线衍射等技术对 AgNPs 进行了表征。此外，评估了 AgNPs 对结直肠腺癌细胞系 HT-29 的细胞毒性作用。通过使用定量聚合酶链反应分析 14 种 mRNA 的表达，研究了这种细胞杀伤作用的机制。结果表明合成的 AgNPs 对 HT-29 细胞具有细胞毒性。分析的所有凋亡基因（包括 cyt-C、p53、Bax、Bcl2、CASP3、CASP8、CASP9 和 CASP12）的表达均上调。自噬相关基因Beclin-1、XBP-1、CHOP、LC3-II表达上调，ATG3、ATG12表达下调。总之，AgNPs 在 HT-29 细胞中诱导线粒体依赖性细胞凋亡和非典型自噬。在这种细胞杀伤作用中，自噬和细胞凋亡之间确实发生了串扰。因此，需要进一步的研究来阐明动物模型中的确切机制，以便在临床医学中进一步使用 AgNPs 治疗消化道肿瘤。而 ATG3 和 ATG12 的表达下调。总之，AgNPs 在 HT-29 细胞中诱导线粒体依赖性细胞凋亡和非典型自噬。在这种细胞杀伤作用中，自噬和细胞凋亡之间确实发生了串扰。因此，需要进一步的研究来阐明动物模型中的确切机制，以便在临床医学中进一步使用 AgNPs 治疗消化道肿瘤。而 ATG3 和 ATG12 的表达下调。总之，AgNPs 在 HT-29 细胞中诱导线粒体依赖性细胞凋亡和非典型自噬。在这种细胞杀伤作用中，自噬和细胞凋亡之间确实发生了串扰。因此，需要进一步的研究来阐明动物模型中的确切机制，以便在临床医学中进一步使用 AgNPs 治疗消化道肿瘤。