Small
·
2025
·
IF 12.1
Xiaozhao Wang,Jing Li,Zhengtao Luo,Zhimin Gao,Yongxin Huang,Jiamin Luo,Xinyi Wang,Yaru Zhang,Meiling Tan,Zhiyao Hou
Insufficient adenosine triphosphate (ATP) can reduce the synthesis of heat-stress-induced heat shock proteins (HSPs) to promote the efficiency of mild photothermal therapy (mPTT), thus the rational design of ATP-exhausted strategy based on nanotechnology is an effective approach to resuscitate mPTT. Herein, Nd 3+ doped nanocrystals (NaYF 4 :Nd@CaF 2 , Nd-NCs) modified hollow mesoporous manganese oxide (H-MnO x ) nanocomposite (H-MnO x @Nd-NCs, MN) is synthesized, and loaded with glucose transporters (GLUTs) inhibitor KL-11743, noted as MN-KL nanozyme. In tumor microenvironment (TME), MN-KL can react with overexpressed glutathione (GSH) to release KL-11743, which can suppress the synthesis of intracellular ATP at the source by blocking glucose uptake to inhibit HSPs expression, meanwhile, MN-KL catalyzes the production of ·O 2 − / 1 O 2 /·OH and lipid peroxidation (LPO) to cleave existing HSPs. Through a two-pronged strategy with ATP inhibition and oxide accumulation, reducing the level of HSPs can be guaranteed for achieving efficient mPTT in both subcutaneous and in situ tumor models in mice. During this process, Nd-NCs can absorb near-infrared light and convert it into heat, and the quenched fluorescence of Nd-NCs by H-MnO x can be recovered through GSH-triggered biodegradation in tumors, thus the modification of Nd-NCs not only provides photothermal effect but also enables MN to own TME-activated fluorescence imaging.
研究领域:
生物医学工程
·
肿瘤学
·
纳米医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOLOGICAL CHEMISTRY
·
2013
·Vol. 289
·期 6
·3339-3351
·
IF 4.651
Weihua Tian,Yu Wang,Yan Xu,Xiangpeng Guo,Bo Wang,Li Sun,Longqi Liu,Fenggong Cui,Qiang Zhuang,Xichen Bao,Gunnar Schley,Tung-Liang Chung,Andrew L. Laslett,Carsten Willam,Baoming Qin,Patrick H. Maxwell,Miguel A. Esteban
Megadose vitamin C (Vc) is one of the most enduring alternative treatments for diverse human diseases and is deeply engrafted in popular culture. Preliminary studies in the 1970s described potent effects of Vc on prolonging the survival of patients with terminal cancer, but these claims were later criticized. An improved knowledge of the pharmacokinetics of Vc and recent reports using cancer cell lines have renewed the interest in this subject. Despite these findings, using Vc as an adjuvant for anticancer therapy remains questionable, among other things because there is no proper mechanistic understanding. Here, we show that a Warburg effect triggered by activation of the hypoxia-inducible factor (HIF) pathway greatly enhances Vc-induced toxicity in multiple cancer cell lines, including von Hippel-Lindau (VHL)-defective renal cancer cells. HIF increases the intracellular uptake of oxidized Vc through its transcriptional target glucose transporter 1 (GLUT1), synergizing with the uptake of its reduced form through sodium-dependent Vc transporters. The resulting high levels of intracellular Vc induce oxidative stress and massive DNA damage, which then causes metabolic exhaustion by depleting cellular ATP reserves. HIF-positive cells are particularly sensitive to Vc-induced ATP reduction because they mostly rely on the rather inefficient glycolytic pathway for energy production. Thus, our experiments link Vc-induced toxicity and cancer metabolism, providing a new explanation for the preferential effect of Vc on cancer cells.
研究领域:
肿瘤学
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药理学
·
细胞生物学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
·
2024
·
IF 8.1
Huilin Chen,Maomao Xie,Wenjie Li,Lipin Tan,Xiaoming Cai,Mingjing Shen,Ruibin Li
The extensive use of synthetic antioxidants, notably N-(1,3-dimethylbutyl)-N′-phenyl- p -phenylenediamine (6-PPD), in rubber-related products, particularly in tire manufacturing, has induced concerns regarding their environmental impact and potential health hazards. Despite the identification of 6-PPD and its derivative, 6-PPD quinone (6-PPDQ), in various water samples and their lethal effects on certain aquatic species ( e.g. , coho salmon, rainbow trout and brook trout), the levels of airborne 6-PPD/6-PPDQ and their respiratory toxicity remain relatively unexplored. In this study, we aimed to evaluate the respiratory toxicity potential of 6-PPD and its derivatives, with a specific focus on detecting these compounds in airborne particulates and assessing their toxic effects on lung cells. Characterization of four airborne fine particulate (FP) samples revealed spherical morphologies with diameters ranging from 17.7 to 225.7 nm, displaying slight agglomeration and negative surface charge. methanol/acetonitrile extraction followed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) analysis confirmed the presence of both 6-PPD and 6-PPDQ on the surfaces of FPs, with significant variations (0.26–1.05 μg g −1 ) in loading capacity observed among the samples. Subsequent exposure of lung cells (THP-1, BEAS-2B, and A549) to 6-PPD and 6-PPDQ revealed dose-dependent declines in mitochondrial metabolic activity induced by 6-PPD, along with severe membrane damage, ATP depletion, and pro-inflammatory cytokine release. Conversely, 6-PPDQ exhibited negligible toxicity in all tested parameters. These findings underscore the potential health risks associated with airborne 6-PPD exposure and emphasize the importance of further research into the respiratory toxicity of 6-PPD derivatives.
研究领域:
环境科学
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毒理学
·
公共卫生
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2019
·
IF 3.571
Jinling Cui,Mingzhu Yan,Xiaoyi Liu,Shutao Yin,Shangyun Lu,Lihong Fan,Hongbo Hu
Previous studies have shown that selenite, a representative of inorganic form selenium, exerts its anticancer effect by inducing apoptosis in androgen-dependent LNCaP prostate cancer cells, but few studies have determined the nature of cell death induced by selenite in metastatic androgen-refractory PC-3 cells. Our study showed that necrosis-like cell death rather than apoptosis, pyroptosis, or autophagic cell death was caused by selenite in PC-3 cells. Mechanistically, this type of cell death was caused by ATP depletion (26.28 ± 3.39 nmol/mg of control versus 9.12 ± 2.44 nmol/mg of 10 μM selenite treatment) that resulted from phosphofructokinase activity reduction (100.17 ± 0.17% of control versus 21.74 ± 6.65% of 10 μM selenite treatment). Our study also showed that ROS production is necessary for the decrease in cellular ATP levels and in phosphofructokinase activity. To our knowledge, this is the first study showing that selenite can induce necrosis-like cell death in PC-3 cells. Our findings support selenite as an effective compound for the therapy of apoptosis-resistant prostate cancer.
研究领域:
肿瘤学
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细胞生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
CANCER LETTERS
·
2017
·
IF 6.375
Changzheng Wang,Hongwei Lv,Wen Yang,Ting Li,Tian Fang,Guishuai Lv,Qin Han,Liwei Dong,Tianyi Jiang,Beige Jiang,Guangshun Yang,Hongyang Wang
Cholangiocarcinoma (CC) is a devastating malignancy with late diagnosis and poor response to conventional chemotherapy. Recent studies have revealed anti-cancer effect of vitamin C ( l -ascorbic acid, ascorbate) in several types of cancer. However, the effect of l -ascorbic acid (AA) in CC remains elusive. Herein, we demonstrated that AA induced cytotoxicity in CC cells by generating intracellular reactive oxygen species (ROS), and subsequently DNA damage, ATP depletion, mTOR pathway inhibition. Moreover, AA worked synergistically with chemotherapeutic agent cisplatin to impair CC cells growth both in vitro and in vivo. Intriguingly, sodium-dependent vitamin C transporter 2 (SVCT-2) expression was inversely correlated with IC50 values of AA. Knockdown of SVCT-2 dramatically alleviated DNA damage, ATP depletion, and inhibition of mTOR pathway induced by AA. Furthermore, SVCT-2 knockdown endowed CC cells with the resistance to AA treatment. Finally, the inhibitory effects of AA were further confirmed in patient-derived CC xenograft models. Thus, our results unravel therapeutic potential of AA alone or in combination with cisplatin for CC. SVCT2 expression level may serve as a positive outcome predictor for AA treatment in CC.
研究领域:
肿瘤学
·
药理学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2013
·
IF 4.57
Wenjing Li,Xinru Li,Yajie Gao,Yanxia Zhou,Shujin Ma,Yong Zhao,Jinwen Li,Yan Liu,Xinglin Wang,Dongdong Yin
The present study aimed to investigate the effect of monomethoxy poly(ethylene glycol)-block-poly(d,l-lactic acid) (mPEG-PLA) on the activity of P-glycoprotein (P-gp) in Caco-2 cells and further unravel the relationship between PLA chain length in mPEG-PLA and influence on P-gp efflux and the action mechanism. The transport results of rhodamine 123 (R123) across Caco-2 cell monolayers suggested that mPEG-PLA unimers were responsible for its P-gp inhibitory effect. Furthermore, transport studies of R123 revealed that the inhibitory potential of P-gp efflux by mPEG-PLA analogues was strongly correlated with their structural features and showed that the hydrophilic mPEG-PLA copolymers with an intermediate PLA chain length and 10.20 of hydrophilic–lipophilic balance were more effective at inhibiting P-gp efflux in Caco-2 cells. The fluorescence polarization measurement results ruled out the plasma membrane fluidization as a contributor for inhibition of P-gp by mPEG-PLA. Concurrently, mPEG-PLA inhibited neither basal P-gp ATPase (ATP is adenosine triphosphate) activity nor substrate stimulated P-gp ATPase activity, suggesting that mPEG-PLA seemed not to be a substrate of P-gp and a competitive inhibitor. No evident alteration in P-gp surface level was detected by flow cytometry upon exposure of the cells to mPEG-PLA. The depletion of intracellular ATP, which was likely to be a result of partial inhibition of cellular metabolism, was directly correlated with inhibitory potential for P-gp mediated efflux by mPEG-PLA analogues. Hence, intracellular ATP-depletion appeared to be possible explanation to the inhibition mechanism of P-gp by mPEG-PLA. Taken together, the establishment of a relationship between PLA chain length and impact on P-gp efflux activity and interpretation of action mechanism of mPEG-PLA on P-gp are of fundamental importance and will facilitate future development of mPEG-PLA in the drug delivery area.
研究领域:
药学
·
药理学
·
药物递送系统
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产品关联
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2022
·
IF 9.273
Linping Jiang,Kesi Wang,Liyan Qiu
Drug resistance is accountable for the inadequate outcome of chemotherapy in clinics. The newly emerging role of nitric oxide (NO) to conquer drug resistance has been recognized as a potential strategy. However, it remains a great challenge to realize targeted delivery as well as accurate release of NO at desired sites. Herein, we developed a PEGylated indocyanine green (mPEG-ICG) integrated nanovesicle system (PIDA) to simultaneously load doxorubicin hydrochloride (DOX⋅HCl) and the NO donor L-arginine (L-Arg), which can produce NO triggered by NIR light irradiation and exert multimodal therapy to sensitize drug-resistant cancers. Upon 808 nm irradiation, the NO released from PIDA led to a decrease in mitochondrial membrane potential, an increase in ROS and significant ATP depletion in K562/ADR cells, thus inhibiting cell growth and resolving the problem of drug resistance. Consequently, the in vivo experiment on K562/ADR-bearing nude mice indicated that PIDA nanovesicles achieved significant anticancer efficacy with a tumor inhibition rate of 80.8%. Above all, PIDA nanovesicles offer guidance for designing nanoplatforms for drug-resistant cancer treatment.
研究领域:
药学
·
纳米技术
·
癌症研究
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2022
·
IF 6.51
Xiaoying Wang,Yaling Zheng,Liangzhen Qiu,Huizhi Ouyang,Xueya Xu,Wen Xu,Yuqin Zhang,Wei Xu
D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS)-modified carboxymethyl chitosan-rhein (TCR) polymeric micelles (PMs) self-assembled by TCR conjugate were constructed for oral delivery of paclitaxel (PTX). PTX-loaded TCR PMs with a drug loading capacity of 47.52 ± 1.65 % significantly improved the intestinal absorption and oral bioavailability of PTX. TCR PMs loaded with PTX displayed time- and concentration-dependent cytotoxicity in Caco-2, MCF-7 and Taxol-resistant MCF-7 (MCF-7/Taxol) cells. In MCF-7/Taxol cells, PTX-loaded TCR PMs promoted apoptosis and changed cell cycle, and TCR conjugate exhibited a P-gp inhibition ability and caused ATP depletion. Moreover, confocal imaging of intestinal sections, Caco-2 cell uptake assay and in vivo bioimaging using environmental response fluorescence probe suggested that TCR PMs loaded with drugs can be absorbed as a whole through the intestinal epithelium after oral administration, enter systemic circulation, and then get to the tumor site. Remarkably, PTX-loaded TCR PMs displayed a significant antitumor effect in H22 tumor xenograft mice and the MCF-7 or MCF-7/Taxol xenograft zebrafish model, which was related to the inhibitory function of TCR conjugate for P-gp activity and P-gp and MDR1 expression. Functionalized TCR PMs are expected to improve the oral therapeutic efficacy of poorly water-soluble antitumor drugs and treat drug-resistant tumors.
研究领域:
药学
·
肿瘤学
·
生物技术
·
药物递送系统
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FREE RADICAL RESEARCH
·
2023
·
IF 3.3
Yangying Li,Yuda Zhu,Shiyi Li,Yuman Dong,Chengyu Wan,Xiuxian Yu,Guang Xin,Zeliang Wei,Fan Li,Yilan Wang,Kun Zhang,Qingqiu Chen,Cuicui Zhang,E. Wen,Hai Niu,Wen Huang
Severe acute pancreatitis (SAP) is an inflammatory disorder of the exocrine pancreas associated with high morbidity and mortality. SAP has been proven to trigger mitochondria dysfunction in the pancreas. We found that Deoxyarbutin (dA) recovered impaired mitochondrial function. High-temperature requirement protein A2 (HtrA2), a mitochondrial serine protease upstream of PGC-1α, is charge of quality control in mitochondrial homeostasis. The molecular docking study indicated that there was a potential interaction between dA and HtrA2. However, whether the protective effect of dA against SAP is regulated by HtrA2/PGC-1α remains unknown. Our study in vitro showed that dA significantly reduced the necrosis of primary acinar cells and reactive oxygen species (ROS) accumulation, recovered mitochondrial membrane potential (ΔΨm) and ATP exhaustion, while UCF-101 (HtrA2 inhibitor), and SR-18292 (PGC-1α inhibitor) eliminated the protective effect of dA. Moreover, HtrA2 siRNA transfection efficiently blocked the protective of dA on HtrA2/PGC-1α pathway in 266-6 acinar cells. Meanwhile, dA also decreased LC3II/I ration, as well as p62, and increased Parkin expression, while UCF-101 and Bafilomycin A1 (autophagy inhibitor) reversed the protective effect of dA. Our study in vivo confirmed that dA effectively alleviated severity of SAP by reducing pancreatic edema, plasma amylase, and lipase levels and improved the HtrA2/PGC-1α pathway. Therefore, this is the first study to identify that dA inhibits pancreatic injury caused by oxidative stress, mitochondrial dysfunction, and impaired autophagy in a HtrA2/PGC-1α dependent manner.
研究领域:
胃肠病学
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药理学
·
分子生物学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
Foods
·
2025
·Vol. 14
·期 18
·3236
·
IF 5.1
Xiaoyong Huang,Huiting Yang,Chenli Wang,Shiqi Yan,Xiaomin Ren,Zilong Sun
The relentless spread of antimicrobial resistance poses a severe threat to global public health, food safety, and environmental security. Natural products with potent antimicrobial activity offer prospective substitutes for traditional antibiotics and chemical preservatives. Here, we demonstrate that pterostilbene (PT), a natural dietary compound, exhibits rapid lytic activity against methicillin-resistantStaphylococcus aureus(MRSA). PT displayed metabolism-independent bactericidal effects, effectively eradicating dormant persister cells within one hour, though its activity was partially attenuated under anaerobic conditions. Mechanistically, PT disrupted membrane integrity by increasing permeability, dissipating membrane potential, depleting cellular ATP, and suppressing reactive oxygen species (ROS) generation. Its efficacy was modulated by membrane phospholipid composition, with phosphatidylglycerol (PG) and cardiolipin (CL) critically influencing antimicrobial potency. Crucially, PT robustly inhibited MRSA biofilm formation in milk. These findings highlight PT’s potential as a structurally stable, natural antimicrobial for controlling resilient MRSA, particularly against biofilm-associated and persister subpopulations in food systems.
研究领域:
微生物学
·
抗菌研究
·
食品安全
·
天然产物
·
生物化学
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产品关联
DOI
PubMed
高影响因子
Nano Research
·
2018
·Vol. 11
·期 9
·4507-4523
·
IF 7.994
Liang Jianming,Li Ruixiang,He Yuwei,Ling Chengli,Wang Qi,Huang Yongzhuo,Qin Jing,Lu Weigen,Wang Jianxin
Although nanotechnology has been rapidly developed and applied in tumor targeting, the outcome of chemotherapy remains greatly restricted by the toxicity of cytotoxic drugs in normal tissues and cells. Therefore, the development of alternative delivery systems, with few side effects in normal cells, has attracted increasing attention. Energy restriction is a novel and promising approach to cancer treatment, which can restrict tumor growth via inhibition of cellular energy metabolism. In this study, a novel tumor targeting system, based on folate-conjugated bovine serum albumin (BSA), was developed to co-deliver albendazole and nanosilver simultaneously, to restrain the energy metabolism of tumor cells. This nanosystem showed stronger anti-tumor efficacy than those using nanoparticles without folic acid modification, nanosilver, or albendazole, both in vitro and in vivo . This nanosystem depleted cellular ATP via direct inhibition of glycolytic enzymes and mitochondrial damage, resulting in inhibition of proliferation, cell-cycle arrest, and apoptosis of tumor cells. The enhanced anti-tumor activity contributed to the tumor-targeting ability of this system, resulting in specific energy inhibition in tumor cells. Toxicity evaluation was performed to confirm the safety of this system. This nanosystem provides an efficient and safe strategy for tumor therapy.
研究领域:
癌症研究
·
纳米技术
·
药理学
·
分子生物学
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产品关联
DOI
高影响因子
Journal of Translational Medicine
·
2023
·Vol. 21
·期 1
·1-17
·
IF 7.4
Zhang Yafei,Yang Bingqian,Tu Chengwei,Ping Yifan,Chen Shuhong,Wu Tong,Zhao Zheyu,Mao Yixin,Yang Zhan,Cao Zelin,Li Jianmin,Huang Kate,Ding Xi,Wu Gang,Zou Peng,Deng Zhennan,Sun Xiaoyu
Background Oral squamous cell carcinoma (OSCC) is one of the most prevalent and fatal oral cancers. Mitochondria-targeting therapies represent promising strategies against various cancers, but their applications in treating OSCC are limited. Alantolactone (ALT) possesses anticancer properties and also regulates mitochondrial events. In this study, we explored the effects of ALT on OSCC and the related mechanisms. Methods The OSCC cells were treated with varying concentrations and duration of ALT and N -Acetyl- l -cysteine (NAC). The cell viability and colony formation were assessed. The apoptotic rate was evaluated by flow cytometry with Annexin V-FITC/PI double staining. We used DCFH-DA and flow cytometry to detect reactive oxygen species (ROS) production and DAF-FM DA to investigate reactive nitrogen species (RNS) level. Mitochondrial function was reflected by mitochondrial reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and ATP levels. KEGG enrichment analyses determined the mitochondrial-related hub genes involved in OSCC progression. Dynamin-related protein 1 (Drp1) overexpression plasmids were further transfected into the cells to analyze the role of Drp1 in OSCC progression. Immunohistochemistry staining and western blot verified the expression of the protein. Results ALT exerted anti-proliferative and pro-apoptosis effects on OSCC cells. Mechanistically, ALT elicited cell injury by promoting ROS production, mitochondrial membrane depolarization, and ATP depletion, which were reversed by NAC. Bioinformatics analysis showed that Drp1 played a crucial role in OSCC progression. OSCC patients with low Drp1 expression had a higher survival rate. The OSCC cancer tissues presented higher phosphorylated-Drp1 and Drp1 levels than the normal tissues. The results further showed that ALT suppressed Drp1 phosphorylation in OSCC cells. Moreover, Drp1 overexpression abolished the reduced Drp1 phosphorylation by ALT and promoted the cell viability of ALT-treated cells. Drp1 overexpression also reversed the mitochondrial dysfunction induced by ALT, with decreased ROS production, and increased mitochondrial membrane potential and ATP level. Conclusions ALT inhibited proliferation and promoted apoptosis of oral squamous cell carcinoma cells via impairment of mitochondrial homeostasis and regulation of Drp1. The results provide a solid basis for ALT as a therapeutic candidate for treating OSCC, with Drp1 being a novel therapeutic target in treating OSCC.
研究领域:
肿瘤学
·
细胞生物学
·
药理学
·
分子生物学
·
生物信息学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）