NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
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2025
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IF 3.1
Alfaiz Faiz Abdulaziz
The rise of antimicrobial resistance to current antibiotics has driven researchers to discover novel natural compounds with antibacterial properties. This study established a sustainable approach for the biofabrication of gold nanoparticles (GNPs) utilizing Ephedra alata leaf extracts conjugated with environmentally friendly, less-toxic, and chitosan (CS), resulting in chitosan (CS)-loaded gold nanoparticles (CS@GNPs). The characterization of GNPs and CS@GNPs is performed using Fourier transform infrared (FT-IR) spectroscopy, transmission electron microscopy (TEM), and DLS measurements. This investigation evaluated the antioxidant and antibacterial properties of the agar diffusion technique using human pathogens. The IC 50 values for ABTS and DPPH were 12.15 ± 0.031 μg/mL and 22.14 ± 0.51 μg/mL for CS@GNPs. The maximal inhibition of CS@GNPs was 32, 31, 30, and 29 mm at a dose of 200 μg/mL of CS@GNPs against E. coli , K. pneumoniae , S. aureus , and P. aeruginosa . CS@GNPs demonstrated a superior reduction of MDR bacteria compared to GNPs alone. The anticancer activity showed that the liver HepG2 cancer cell lines exhibited greater sensitivity to the toxicity of CPT + GNPs and CPT + CS@GNPs than non-cancerous fibroblast 3T3 cells. The IC 50 values of CPT + GNPs and CPT + CS@GNPs of HepG2 cancer cell lines were 44.32 and 33.15 μg/mL. The research indicates that GNPs and CS@GNPs, in conjunction with CPTGNPs, can efficiently combat cancer at doses where the cisplatin (CPT) proves ineffective, resulting in a significant decrease in the necessary dosage for observed antitumor efficacy.
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高影响因子
Frontiers in Pharmacology
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2025
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IF 4.8
Xiaoli Deng,Chunjie Hu,Lin Li,Guixian Yang,Chikun Li,Wanxun Zhang,Guangyu Cheng
Background Lung cancer is a leading cause of cancer-related deaths, with cisplatin being a cornerstone of treatment. However, resistance to cisplatin presents a significant challenge. β-elemene, a natural compound, has demonstrated potential to reverse cisplatin resistance. LncRNA LINC00511 has been implicated in cisplatin resistance through its role in activating the PI3K/AKT/mTOR pathway, which supports tumor survival and proliferation. Purpose This study aims to investigate the mechanism by which β-elemene overcomes cisplatin resistance in lung cancer by regulating LINC00511. Methods Human lung adenocarcinoma cells (A549 and A549/DDP) were treated with β-elemene and cisplatin. Cell proliferation and apoptosis were assessed using CCK-8, EdU staining, and flow cytometry. LINC00511 expression was measured by qRT-PCR, and protein levels of PI3K, AKT, and mTOR were evaluated via Western blot. A xenograft model was used to confirm in vivo effects. Results β-elemene significantly enhanced cisplatin-induced apoptosis in A549/DDP cells, reduced LINC00511 expression, and inhibited the PI3K/AKT/mTOR pathway. LINC00511 knockdown further potentiated these effects, both in vitro and in vivo . Xenograft models confirmed the enhanced anti-tumor effects of the combination treatment. Conclusion β-elemene overcomes cisplatin resistance in lung cancer by downregulating LINC00511 and inhibiting the PI3K/AKT/mTOR pathway. These findings propose a promising therapeutic strategy for treating cisplatin-resistant lung cancer.
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NANOTECHNOLOGY
·
2025
·Vol. 36
·期 30
·305101
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IF 2.8
Gaojian Liu,Wenjing Wen,Xuan Zhao,Yanan Jing,Hao Li,Xulong Fan,ZiXuan Huang,Gaofeng Liang
Breast cancer is the most prevalent fatal cancer among women worldwide and the leading cause of death for women. Ferroptosis is a form of programmed cell death that relies on iron and is non-apoptotic, triggered by the inhibition of the cellular antioxidant system. Photodynamic therapy (PDT) employs photosensitizers to produce reactive oxygen species (ROS), increasing oxidative stress in tumor cells. When combined with ferroptosis, PDT can work synergistically to regulate intracellular redox balance. In this study, we designed engineered nano-erythrocyte membranes for targeted delivery of Chlorin e6 (Ce6) and cisplatin (DDP) to enhance breast cancer treatment. By using mild ultrasound, Ce6 and DDP were co-loaded onto the nano-erythrocyte membranes, combining ferroptosis inducers and photosensitizers to combat breast cancer. To improve targeting capability towards breast cancer, RGD cyclic peptides were modified onto the nano-erythrocyte membranes through a thiol–maleimide coupling reaction. The RGD-modified nano-erythrocyte membranes co-loaded with Ce6 and DDP not only inherited the good stability and significant biocompatibility of red blood cell membranes but also promoted the uptake by breast cancer cells, effectively inducing ferroptosis in these cells. In conclusion, this multifunctional ‘natural’ nanodrug delivery system provides an effective and safe method for PDT combined with ferroptosis for breast cancer treatment.
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ARCHIVES OF TOXICOLOGY
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2025
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IF 6.9
Tang Wei,Zong Shimin,Du Peiyu,Yu Xuan,Li Ting,Liu Bo,Zhong Yu,Lei Wenyang,Yu Wenting,Xiao Hongjun
Cochlear hair cell death is the primary cause of cisplatin-induced ototoxicity, currently lacking widely applicable clinical methods for effective prevention and treatment. In this study, an in vivo cisplatin-induced ototoxicity model was established by intraperitoneal injection of 12 mg/kg cisplatin. We found that ablation of SIRT3 exacerbates cisplatin-induced hearing loss and cochlear hair cell damage. An in vitro cisplatin-induced ototoxicity model was established using 5 µM cisplatin in cochlear explants and OC-1 cells. We found that the absence of SIRT3 impairs cochlear hair cell glycolytic metabolism, leading to excessive accumulation of ROS and significant reduction in MMP levels, thereby promoting apoptosis. In contrast, overexpression of SIRT3 in OC-1 cells promotes cochlear hair cell survival and reduces cochlear hair cell apoptosis. Inhibition of PFKFB3 reduces glycolytic metabolism in OC-1 cells, and the protective effect conferred by SIRT3 overexpression is lost. In summary, the protective effect of SIRT3 may be mediated by the regulation of PFKFB3-dependent glycolysis and the mitigation of cisplatin-induced excessive ROS accumulation.
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Frontiers in Pharmacology
·
2025
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IF 4.8
Yuru Pang,Qiqi Meng,Yangchen Cui,Shiyi Liu,Huihui Jiang,Chenlan Xu,Yan An,Yang Jiao,Qi Zhang,Jihua Nie
Background: Lung cancer is the leading cause of cancer-related death in the worldwide. Although cisplatin and other platinum-based drugs are widely used as radiosensitizers in radiotherapy and considered the first-line treatment for advanced lung cancer, their clinical utility is often limited by drug resistance and severe cytotoxic side effects. In recent years, iridium-based complexes and other transition metal cation complexes with similar structural properties have garnered increasing research interest due to their potential anticancer properties.Methods: Recently, we synthesized a novel iridium (III) complex (Ir-1) and evaluated its safety and stability. The present study aimed to identify Ir-1 with potent anticancer activity by assessing its cytotoxic effects on lung cancer cells in vitro. Additionally, it investigated Ir-1's radiosensitizing efficacy and the underlying mechanisms.Results: The results demonstrated that Ir-1 exhibited significant radiosensitizing effects on lung cancer cells. Ir-1 effectively reduced cell viability and colony formation, arrested the cell cycle at the G2/M phase, inhibited cell migration and invasion, decreased mitochondrial membrane potential, and increased reactive oxygen species (ROS) generation in lung cancer cells. Importantly, these cytotoxic effects were selective, with minimal impact on normal cells. Mechanistic studies showed that Ir-1 enhanced radiation-induced cancer cell death by disrupting mitochondrial function and activating the mitochondrial apoptotic pathway. This was evidenced by upregulated expression levels of Bax, Cytochrome c (Cyt-C), and Caspase9 proteins, along with reduced level of Bcl-2 protein. Notably, the addition of a Cyt-C inhibitor significantly reduced the expression of Cyt-C and Caspase9 proteins. Similarly, treatment with the Caspase9 inhibitor Z-LEHD-FMK also reduced Caspase9 protein level.Conclusion: This study provides robust evidence that Ir-1 is a promising and safe radiosensitizer for lung cancer therapy. Its ability to enhance radiation-induced cytotoxicity through mitochondrial dysfunction and activation of apoptotic pathways highlights its potential for clinical application.
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PHYTOMEDICINE
·
2024
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IF 6.7
Lujuan Han,Xiaohan Xiang,Yuhui Fu,Sisi Wei,Cong Zhang,Lei Li,Yueping Liu,Huilai Lv,Lianmei Zhao,Baoen Shan
Background Esophageal squamous cell carcinoma (ESCC) is the predominant histological subtype of esophageal cancer (EC) in China, and demonstrates varying levels of resistance to multiple chemotherapeutic agents. Our previous studies have proved that periplocin (CPP), derived from the extract of cortex periplocae, exhibiting the capacity to hinder proliferation and induce apoptosis in ESCC cells. Several studies have identified additional anti-cancer constituents in the extract of cortex periplocae, named periplcymarin (PPM), sharing similar compound structure with CPP. Nevertheless, the inhibitory effects of PPM on ESCC and their underlying mechanisms remain to be further elucidated. Purpose The aim of this study was to investigate function of PPM inhibiting the growth of ESCC in vivo and in vitro and to explore its underlying mechanism, providing the potential anti-tumor drug for ESCC. Methods Initially, a comparative analysis was conducted on the inhibitory activity of three naturally compounds obtained from the extract of cortex periplocae on ESCC cells. Among these compounds, PPM was chosen for subsequent investigation owing to its comparatively structure and anti-tumor activity simultaneously. Subsequently, a series of biological functional experiments were carried out to assess the impact of PPM on the proliferation, apoptosis and cell cycle arrest of ESCC cells in vitro . In order to elucidate the molecular mechanism of PPM, various methodologies were employed, including bioinformatics analyses and mechanistic experiments such as high-performance liquid chromatography combined with mass spectrometry (HPLC-MS), cell glycolysis pressure and mitochondrial pressure test. Additionally, the anti-tumor effects of PPM on ESCC cells and potential toxic side effects were evaluated in vivo using the nude mice xenograft assay. Results Our study revealed that PPM possesses the ability to impede the proliferation of ESCC cells, induce apoptosis, and arrest the cell cycle of ESCC cells in the G2/M phase in vitro . Mechanistically, PPM exerted its effects by modulating glycolysis and mitochondrial oxidative phosphorylation (OXPHOS), as confirmed by glycolysis pressure and mitochondrial pressure tests. Moreover, rescue assays demonstrated that PPM inhibits glycolysis and OXPHOS in ESCC cells through the PI3K/AKT and MAPK/ERK signaling pathways. Additionally, we substantiated that PPM effectively suppresses the growth of ESCC cells in vivo , with only modest potential toxic side effects. Conclusion Our study provides novel evidence that PPM has the potential to simultaneously target glycolysis and mitochondrial OXPHOS in ESCC cells. This finding highlights the need for further investigation into PPM as a promising therapeutic agent that targets the tumor glucose metabolism pathway in ESCC.
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JOURNAL OF NANOBIOTECHNOLOGY
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2025
·Vol. 23
·期 1
·1-23
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IF 12.6
Zou Lan,Wang Rujing,Zhao Mengnan,Li Yuke,Sun Chen,Xie Jinjin,Chen Yan,Jing Qian,Mi Dandan,Shi Sanjun
Pyroptosis, a recently identified cellular demise regulated by gasdermin family proteins, is emerging as a promising avenue in cancer immunotherapy. However, the realm of light-controlled pyroptosis in cancer cells remains largely unexplored. In this study, we took a deliberate approach devoid of any chemical alterations to develop a novel photosensitizer called “pharmaceutical-dots (pharm-dots)” by combining nonemissive polymers (Poly (lactic-co-glycolic acid), PLGA) with nonfluorescent invisible molecules like curcumin, berberine, oridonin into PLGA nanoparticles (PLGA-NPs). Initially, our research commenced with a comprehensive mechanistic comparison study, consolidating fragmented information on optical mechanisms. This exploration revealed that surface passivation atoms play a dominant role in governing the fluorescence emission of PLGA-NPs. Remarkably, these new luminophores, composed of two non-inherently luminous components, exhibit a remarkable synergistic boost in photoluminescence through a “0 + 0 > 2” phenomenon. In-depth investigations uncovered that these luminous PLGA-NPs, capable of generating 1 O 2 , induce pyroptosis under photoexcitation conditions through the caspase-3/gasdermin E (GSDME) pathway. Simultaneously, our findings highlight PLGA-NPs as a novel optical formulation suitable for imaging, displaying substantial biological activity when paired with photoirradiation. This discovery holds the potential to facilitate the application of light-controlled pyroptosis in antitumor therapy, marking a promising stride toward innovative approaches in cancer treatment. Graphical abstract
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NEW JOURNAL OF CHEMISTRY
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2025
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IF 2.5
Xiong-Li Liu,Jing Lou,Xian-Qiao Zhu,Di-Cheng Pan,De-Wu Liu,Hui-Xian Jing,Wenjing Zhang,Hong-Xing Cen,Guo-Deng Guo-Deng Dong
The development of single chiral source-derived ligands to fine-switch enantioselectivity has continuously attracted the attention in asymmetric catalysis. Herein, we use the same chiral source L-prolinamide as the starting material, synthesizing chiral bidentate pyridine-type N-oxide ligands (denoted as Py-NO) and chiral monodentate phenyl N-oxide ligands (denoted as Ph-NO); their effectiveness was demonstrated in the switch of enantioselectivity in palladium(II)-catalysed Friedel-Crafts (FC) alkylation of indoles and 2,3-dioxopyrrolidines, and both enantiomers of structurally important indole derivatives can be prepared in good yields (up to 91% yield) and high enantioselectivities (up to 99% ee). Key to the success of switch of enantioselectivity is the existence of two different activation patterns in this palladium(II) catalytic system. Experiments demonstrated that a counteranion would plausibly coordinate to the palladium(II) center in the stereoselectivity-determining step. Preliminary mechanistic studies provide a rational explanation for the above observations. This study was the first example of monodentate ligand in asymmetric catalytic Friedel-Crafts alkylation.
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