Biosynthetic Silver Nanoparticles Inhibit the Malignant Behavior of Gastric Cancer Cells and Enhance the Therapeutic Effect of 5-Fluorouracil by Promoting Intracellular ROS Generation and Apoptosis

Yuan, Jingwen; Khan, Shahid Ullah; Luo, Jiajun; Jiang, Yue; Yu, Yang; Yan, Junfeng; Tong, Qiang

doi:10.3390/pharmaceutics14102109

Cited by 14 publications

(17 citation statements)

References 30 publications

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“…Additionally, Ca 2+ is closely involved in a bidirectional relationship with ROS generation (33). Several studies showed the capability of AgNPs to induce aberrant ROS production, resulting in the induction of the mitochondrial apoptosis pathway, in different cancer cell lines, including chronic myeloid leukemia, breast, gastric and pancreatic cancer (10,28,(34)(35)(36). We showed that AgNPs induced ROS overproduction in HG-3 cells after 2h-treatment, time at which cell viability was already strongly reduced.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic targeting of chronic lymphocytic leukemia by silver nanoparticles

Adamo

Barcelos

Falco

et al. 2023

Preprint

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Background Chronic lymphocytic leukemia (CLL) is an incurable disorder associated with alterations in several pathways essential for survival and proliferation. Despite the advances obtained in CLL therapy with the new target agents, in some cases relapses and resistances could occur making necessary the finding of new alternatives to manage CLL refractoriness. To provide new therapeutic strategies for CLL, we investigated the anti-leukemic activity of silver nanoparticles (AgNPs), whose impact on CLL cells has been poorly explored.Methods We studied the action mechanisms of AgNPs in vitro by flow-cytometry and molecular analyses. To improve bioavailability of AgNPs, we generated AgNPs coated with the anti-CD20 antibody Rituximab (AgNPs@Rituximab) and carried out imaging-based approaches and in vivo experiments to evaluate specificity, drug uptake and efficacy.Results AgNPs reduced viability of CLL primary cells and HG-3 cell line by activating intrinsic apoptotic pathway characterized by Bax/Bcl-2 unbalance, caspase activation and PARP degradation. Early apoptotic events triggered by AgNPs included enhanced Ca2+ influx and ROS overproduction. AgNPs synergistically potentiated the cytotoxicity of Venetoclax, Ibrutinib and Bepridil. In vitro, AgNPs@Rituximab conjugates were rapidly internalized within CLL cells and in vivo, they strongly prolonged survival of CLL xenograft models compared to each unconjugated single agent.Conclusions AgNPs showed a strong anti-leukemic activity in CLL with the potential to clinical translation in combination with agents used in CLL. The increased specificity of AgNPs@Rituximab toward CLL cells could be relevant for overcoming in vivo AgNPs non-specific distribution and for increasing their efficacy.

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Section: Discussionmentioning

confidence: 99%

Therapeutic targeting of chronic lymphocytic leukemia by silver nanoparticles

Adamo

Barcelos

Falco

et al. 2023

Preprint

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“…Similarly, activation of ATF2 during sorafenib‐induced ferroptosis has been observed, and knockdown of ATF2 was found to promote sorafenib‐induced ferroptosis achieved through the inhibition of SLC7A11 expression mediated by HSPH1, a downstream target of ATF2 124 . Baicalin, a flavonoid derived from Scutellaria baicalensis Georgi , has been demonstrated to enhance the effectiveness of 5‐fluorouracil in GC by promoting ROS‐mediated ferroptosis 161 . Furthermore, STAT3 has been recognized as a modulator of crucial ferroptosis‐related genes, including GPX4 , SLC7A11 , and FTH1 .…”

Section: Ferroptosis In Gcmentioning

confidence: 94%

Targeting ferroptosis in gastric cancer: Strategies and opportunities

Le,

Pan,

Zhang

et al. 2023

Immunological Reviews

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SummaryFerroptosis is a novel form of programmed cell death morphologically, genetically, and biochemically distinct from other cell death pathways and characterized by the accumulation of iron‐dependent lipid peroxides and oxidative damage. It is now understood that ferroptosis plays an essential role in various biological processes, especially in the metabolism of iron, lipids, and amino acids. Gastric cancer (GC) is a prevalent malignant tumor worldwide with low early diagnosis rates and high metastasis rates, accounting for its relatively poor prognosis. Although chemotherapy is commonly used to treat GC, drug resistance often leads to poor therapeutic outcomes. In the last several years, extensive research on ferroptosis has highlighted its significant potential in GC therapy, providing a promising strategy to address drug resistance associated with standard cancer therapies. In this review, we offer an extensive summary of the key regulatory factors related to the mechanisms underlying ferroptosis. Various inducers and inhibitors specifically targeting ferroptosis are uncovered. Additionally, we explore the prospective applications and outcomes of these agents in the field of GC therapy, emphasizing their capacity to improve the outcomes of this patient population.

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“…showed that ZnO‐NPs could induce ER stress in mouse ovarian cells through the Keap/Nrf2 signaling pathway and cause apoptosis. Yuan et al 268 . showed that biosynthetic Ag‐NPs inhibited the malignant behavior of gastric cancer cells and enhanced the therapeutic effect of 5‐fluorouracil by promoting intracellular ROS generation and apoptosis.…”

Section: Toxicological Mechanisms Of Npsmentioning

confidence: 99%

“…[263][264][265][266] The study by Xu et al 267 showed that ZnO-NPs could induce ER stress in mouse ovarian cells through the Keap/Nrf2 signaling pathway and cause apoptosis. Yuan et al 268 showed that biosynthetic Ag-NPs inhibited the malignant behavior of gastric cancer cells and enhanced the therapeutic effect of 5-fluorouracil by promoting intracellular ROS generation and apoptosis. Li et al 269 showed that titania-NPs enhanced testicular apoptosis and DNA damage caused by cypermethrin and promoted oxidative stress in testicular tissue.…”

Section: Studies Between Nps and Apoptosismentioning

confidence: 99%

Nanoparticles‐induced potential toxicity on human health: Applications, toxicity mechanisms, and evaluation models

Xuan

Zhao

Skonieczna

et al. 2023

MedComm

110

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Nanoparticles (NPs) have become one of the most popular objects of scientific study during the past decades. However, despite wealth of study reports, still there is a gap, particularly in health toxicology studies, underlying mechanisms, and related evaluation models to deeply understanding the NPs risk effects. In this review, we first present a comprehensive landscape of the applications of NPs on health, especially addressing the role of NPs in medical diagnosis, therapy. Then, the toxicity of NPs on health systems is introduced. We describe in detail the effects of NPs on various systems, including respiratory, nervous, endocrine, immune, and reproductive systems, and the carcinogenicity of NPs. Furthermore, we unravels the underlying mechanisms of NPs including ROS accumulation, mitochondrial damage, inflammatory reaction, apoptosis, DNA damage, cell cycle, and epigenetic regulation. In addition, the classical study models such as cell lines and mice and the emerging models such as 3D organoids used for evaluating the toxicity or scientific study are both introduced. Overall, this review presents a critical summary and evaluation of the state of understanding of NPs, giving readers more better understanding of the NPs toxicology to remedy key gaps in knowledge and techniques.

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Biosynthetic Silver Nanoparticles Inhibit the Malignant Behavior of Gastric Cancer Cells and Enhance the Therapeutic Effect of 5-Fluorouracil by Promoting Intracellular ROS Generation and Apoptosis

Cited by 14 publications

References 30 publications

Therapeutic targeting of chronic lymphocytic leukemia by silver nanoparticles

Therapeutic targeting of chronic lymphocytic leukemia by silver nanoparticles

Targeting ferroptosis in gastric cancer: Strategies and opportunities

Nanoparticles‐induced potential toxicity on human health: Applications, toxicity mechanisms, and evaluation models

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