JOURNAL OF CELLULAR BIOCHEMISTRY
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2018
·Vol. 120
·期 1
·634-644
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IF 2.959
Shengcai Yang,Dawei Zhang,Na Shen,Guanyi Wang,Zhaohui Tang,Xuesi Chen
Ovarian cancer is the major cause of death in women gynecological malignancy and gemcitabine (GEM) is commonly used in related chemotherapy. However, more than 90% GEM is catalyzed into an inactive metabolite 2′-deoxy-2′,2′-difluorouridine by stromal and cellular cytidine deaminase (CDA). Dihydroartemisinin (DHA), which possesses an intramolecular endoperoxide bridge, could be activated by heme or ferrous iron to produce reactive oxygen species (ROS). The excess ROS generation will excite expression of heme oxygenase-1 and suppress CDA expression. Under low CDA expression, the inactivation of GEM is decreased in turn to exert excellent therapeutic efficiency. Herein, we first studied the ROS generation by DHA in vitro with A2780 cells by means of flow cytometry and confocal laser scanning microscopy. Furthermore, cytotoxicity assay in vitro showed that DHA + GEM had synergistic effect, with molar ratio of DHA and GEM at 10. Eventually, in A2780 ovarian cancer xenograft tumor model, DHA + GEM exhibited significant antitumor efficiency with lower blood toxicity than GEM alone. Noteworthy, the combination treatment group completely eliminated the tumors on day 14.
研究领域:
肿瘤学
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药理学
·
分子生物学
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DOI
PubMed
高影响因子
BIOMATERIALS
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2015
·
IF 8.557
Peisheng Zhang,Xiao-fang Jiang,Xuezheng Nie,Yong Huang,Fang Zeng,Xitao Xia,Shuizhu Wu
Currently drug-induced liver injury (DILI) has become a major and challenging public health issue in terms of medicine development and clinical therapy. The level of γ-glutamyl transpeptidase (GGT) has long been regarded as a preclinical/clinical biomarker for prediction of DILI. Herein, we report a two-photon fluorescent sensor for tracking GGT level changes resulted from DILI in vivo. The sensor was prepared by linking a glutamic acid to a dicyanomethylene-4H-pyran (DCM) derivative; and the presence of GGT cleaves γ-glutamyl amide group from the sensor and thereby restores the fluorescence emission (at 635 nm) of DCM moiety under femtosecond pulses at 800 nm. This two-photon sensor exhibits superior sensing performance such as red emission, high photostability and low detection limit (∼0.057 U/L). On a two-photon microscope, the sensor shows a bright red fluorescence in GGT-overexpressing A2780 cells; and it can fluorescently respond to the GGT generated in the liver of zebrafishes as a result of clinical drug (phenytoin) treatment. These findings demonstrate that a commonly-used clinical drug phenytoin can cause remarkable elevation in GGT level in liver, and this sensor may be useful as a marker to detect clinical drug-induced organ damages.
研究领域:
药理学
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医学成像
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毒理学
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生物医学工程
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DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2025
·
IF 3.5
Qile Xia,Beiqiong Hao,Chenxing Liu,Yan Cao
Polygonatum cyrtonema Hua (PcH) is a traditional medicinal and edible homologous plant. Here, the anticancer activity of different purified PcH saponins (PcHs) on the ovarian cancer (OC) cell A2780 were investigated. The PcHs were purified by AB-8. Their effects on the apoptosis, migration and invasion of A2780 were explored by CCK8, wound healing assay, Hoechst 33258 staining, Annexin V-FITC/PI and intracellular reactive oxygen species (ROS) measurement. Moreover, western blot and realtime-PCR confirmation were performed for the associated protein and mRNA targets. The results showed that the content of PcHs increased from 0.31 ± 0.02 mg/mL to 0.79 ± 0.02 mg/mL after purification. The inhibition rate of purified PcHs on A2780 could reach 66.76 ± 0.56%. Specifically, it promoted cell apoptosis, disturbed the cell cycle, increased the ROS levels, regulated the expression levels of pro-apoptotic and anti-apoptotic proteins. PcHs can also regulate the expression level of proteins related to the invasion and migration characteristics of A2780, the mRNA expression level related to the P13K-Akt signal transduction process, and the extracellular matrix-receptor interaction pathway, as well as drug resistance. Overall, this study provides a new idea for the treatment of OC.
研究领域:
肿瘤学
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药理学
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细胞生物学
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传统中药
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DOI
PubMed
高影响因子
Journal of Integrative Medicine-JIM
·
2024
·
IF 4.2
Zhen Wang,Min Liu,Guang-xing Li,Liu Zhang,Kai-yue Ding,Si-qi Li,Bing-qing Gao,Peng Cheng,Hyok-Chol Choe,Lun-yue Xia,Yu-tong Yang,Yi Liu,Xue Sui,Jun-nan Ma,Lin Zhang
Objective Despite the combination of Scutellaria barbata D. Don and Scleromitrion diffusum (Willd.) R.J. Wang (SB-SD) being a recognized Chinese medicinal herbal pair that is commonly used in the treatment of ovarian cancer, there is a poor understanding of their pharmacological mechanisms. This study examines the antitumor properties and potential mechanisms of SB-SD on human ovarian cancer A2780 cells through a multi-omics approach, establishing a pharmacological basis for clinical utilization. Methods A range of mass ratios and reagents were used in the hot reflux extraction of SB-SD. The inhibitory effect of the SB-SD extracts on A2780 cell proliferation was assessed using the cell-counting kit 8 assay. A zebrafish tumor implantation model was used to evaluate the effects of SB-SD extracts on tumor growth and metastasis in vivo. Transcriptomics and proteomics were used to investigate alterations in biological pathways in A2780 cells after treatment with different concentrations of SB-SD extract. Cell cycle, cell apoptosis, intracellular free iron concentration, intracellular reactive oxygen species (ROS) concentration, malondialdehyde (MDA), and mitochondrial membrane potential were measured. Real-time quantitative reverse transcription polymerase chain reaction and Western blotting were utilized to investigate the effects of heme catabolism and ferritinophagy on ferroptosis induced by SB-SD extract in A2780 cells. Results The 70% ethanol extract of SB-SD (a mass ratio of 4:1) inhibited A2780 cell proliferation significantly with a half maximal inhibitory concentration of 660 μg/mL in a concentration- and time-dependent manner. Moreover, it effectively suppressed tumor growth and metastasis in a zebrafish tumor implantation model. SB-SD extract induced the accumulation of free iron, ROS, MDA, and mitochondrial damage in A2780 cells. The mechanisms might involve the upregulated expression of ferritinophagy-related genes microtubule-associated protein 1 light chain 3, autophagy-related gene 5, and nuclear receptor coactivator 4. Conclusions SB-SD extract effectively inhibited the development of ovarian cancer both in vitro and in vivo. Its mechanism of action involved inducing ferroptosis by facilitating heme catabolism and ferritinophagy. This herbal pair holds promise as a potential therapeutic option for ovarian cancer treatment and may be utilized in combination with routine treatment to improve the treatment outcomes of ovarian cancer patients.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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