MOLECULES
·
2024
·Vol. 29
·期 4
·872
·
IF 4.2
Ying Zhao,Zhang-Gui Ding,Yu-Jie Yan,Rui Yang,Miao-Miao Qi,Shu-Kang Pan,Ji-Ling Xie,Yu-Hui Sun,Jin Xiang
Breast cancer is a significant threat to life and health, which needs more safe and effective drugs to be explored. Teadenol B is a characteristic chemical component of microbial fermented tea. This study discovered that teadenol B could exhibit obvious inhibitory effects on all four different clinical subtype characteristics of breast cancer cells. Proteomic studies show that deoxycytidine triphosphate deaminase (DCTD), which could block DNA synthesis and repair DNA damage, had the most significant and consistent reduction in all four types of breast cancer cells with the treatment of teadenol B. Considering MDA-MB-231 cells exhibit poor clinical prognosis and displayed substantial statistical differences in KEGG pathway enrichment analysis results, we investigated its impact on the size and growth of MDA-MB-231 triple-negative breast tumors transplanted into nude mice and demonstrated that teadenol B significantly suppressed tumor growth without affecting body weight significantly. Finally, we found that the conversion of LC3-I to LC3-II in MDA-MB-231 increased significantly with teadenol B treatment. This proved that teadenol B could be a strong autophagy promotor, which explained the down-regulation of DCTD to some extent and may be the potential mechanism underlying teadenol B’s anti-breast cancer effects. This finding provides new evidence for drinking fermented tea to prevent breast cancer and highlights the potential of teadenol B as a novel therapeutic option for breast cancer prevention and treatment, necessitating further investigations to clarify its exact target and the details involved.Keywords:teadenol B;breast cancer;autophagy
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
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2018
·
IF 3.974
Bin Li,Bowen Gu,Zhaoguang Yang,Ting Zhang
Arsenic contamination of water is a global concern due to its heavy threat to human health. In this study, the submerged macrophyte Vallisneria natans (Lour.) Hara was used to remove environmentally relevant concentrations of arsenic in the binary As(III)/As(V) system. The concentrations of total arsenic (tAs) and As(III) in water dropped rapidly within 3 days, while As(V) first increased slightly within 3 days and then gradually decreased. About 1.2% dimethylarsinate (DMA) was detected at the 14th day of treatment. These findings indicated that As(III) could be oxidized to As(V) and methylated to DMA in water with V. natans . In relation to V. natans , both tAs and As(V) were much higher in roots compared to leaves. Arsenate was the predominant species (≥ 95.65 ± 0.10%) in roots, and As(III) was only found at the 14th day (3.45–6.96 mg kg –1 ). In leaves, As(III) significantly increased ( P < 0.05) as the treatment duration increased. The proportions of As(V) (27.99–40.03%) were lower than those of As(III) and arsenobetaine (AsB) was detected (0.52–1.87 mg kg –1 ) after 7 d. The results of arsenic speciation demonstrated that the transformation of arsenic species in V. natans included As(V) reduction and As(III) methylation to AsB. There were a decrease in chlorophyll content, and an increase in MDA level and antioxidant enzymes (SOD, CAT , and POD) activities. The MDA level was much higher in leaves than roots, whereas the activities of SOD, CAT, and POD were the opposite, suggesting their possible role in arsenic resistance and detoxification. Our results indicate the potential of V. natans in phytoremediation of arsenic-contaminated water.
研究领域:
环境科学
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植物修复
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水生生态学
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毒理学
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产品关联
DOI
PubMed
高影响因子
LIFE SCIENCES
·
2020
·
IF 3.647
Shujun Wang,Wei Liu,Jin Wang,Xia Bai
Curculigoside (CUR) is natural ingredient from Curculigo orchioides Gaertn with multiple biological activities. However, whether CUR protects from ulcerative colitis (UC) and underlying mechanisms are unclear. Herein, mice challenged with dextran sulfate sodium (DSS) were established and administrated with CUR for 7 days. Then histological pathologies and ferroptosis regulators were determined in vivo . The ferroptotic IEC-6 cells were prepared to investigate the underlying mechanism of CUR. Results showed that CUR inhibited the disease activity index, histological damage and cell death in mice with colitis. We also found that ferroptosis was induced in mice with colitis, as evidenced by iron overload, GSH depletion, ROS and MDA production, accompanied by decreased expression of SOD and GPX4. CUR treatment significantly reversed these alterations of ferroptotic features in DSS-induced mice. Furthermore, similar effects of CUR on ferroptosis were observed in IEC-6 cells under the combined treatment of H 2 O 2 and iron chloride hexahydrate. Interestingly, we found that CUR could increase the selenium sensitivity and promote GPX4 transcription level in IEC-6 cells. Knockdown of GPX4 significantly blocked the protective effects of CUR on cell death, GSH and MDA contents as well as LDH activity in ferroptotic IEC-6 cells. Taken together, these findings suggest that CUR protects against ferroptosis in UC by the induction of GPX4, which presents a potential agent for UC treatment.
研究领域:
药理学
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胃肠病学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2023
·
IF 6.8
Yan Wang,Yue Zhang,Jinglong Xue,Leqiang Gao,Xiangyang Li,Moxuan Zhao,Dong Zhao,Xianqing Zhou
Decabromodiphenyl ether (BDE-209) is an environmental toxin. Increasing evidence showed that BDE-209 exposure induced liver injury, but the mechanism still remains unknown. The present study explored the effect and mechanism of ferroptosis on hepatotoxicity triggered by BDE-209 in vivo and in vitro . In vivo experiment, ICR mice were exposed to BDE-209 for 50 days, and then recovered for 50 days; HepG2 and L02 cells were treated with BDE-209 or/and ferrostatin-1 (Fer-1) for establishing in vitro model. In vivo , the results showed that BDE-209 accumulated in liver and induced liver damage, increased Fe 2+ and MDA contents, and blocked the activation of SLC7A11/GSH/GPX4 pathway in liver; BDE-209 also activated IKK/IκB/NF-κB pathway and elevated inflammatory cytokines levels in liver after exposure for 50 days. After BDE-209 stopping exposure 50 days, the severity of liver damage, ferroptosis and inflammatory response were still higher than the corresponding control group. In vitro , ferroptosis inhibitor Fer-1 rescued ferroptotic damage and attenuated cell death in BDE-209-treated HepG2 and L02 cells. In addition, Fer-1 reversed the activation of IKK/IκB/NF-κB pathway and the increase of pro-inflammatory cytokines levels in BDE-209-treated HepG2 and L02 cells. Together, the above results suggested that BDE-209 induced tissue damage and inflammatory response by activating ferroptosis through increasing iron-dependent lipid peroxidation and blocking the activation of SLC7A11/GSH/GPX4 pathway in liver, indicating that ferroptosis is a potential mechanism for BDE-209-induced hepatotoxicity.
研究领域:
毒理学
·
肝病学
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细胞生物学
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环境科学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2023
·
IF 6.7
Xinxin Li,Cheng Wang,Shang Li,Fucheng Yin,Heng Luo,Yonglei Zhang,Zhongwen Luo,Yifan Chen,Siyuan Wan,Lingyi Kong,Xiaobing Wang
Currently available PARP inhibitors are mainly used for the treatment of BRCA-mutated triple-negative breast cancer (TNBC), with a narrow application range of approximately 15% of patients. Recent studies have shown that EZH2 inhibitors have an obvious effect on breast cancer xenograft models and can promote the sensitivity of ovarian cancer cells to PARP inhibitors. Here, a series of new dual-target PARP1/EZH2 inhibitors for wild-BRCA type TNBC were designed and synthesized. SAR studies helped us identify compound 12e , encoded KWLX-12e , with good inhibitory activity against PARP1 (IC 50 = 6.89 nM) and EZH2 (IC 50 = 27.34 nM). Meanwhile, KWLX-12e showed an optimal cytotoxicity against MDA-MB-231 cells (IC 50 = 2.84 μM) and BT-549 cells (IC 50 = 0.91 μM), with no toxicity on normal breast cell lines. KWLX-12e also exhibited good antitumor activity with the TGI value of 75.94%, more effective than Niraparib plus GSK126 (TGI = 57.24%). Mechanistic studies showed that KWLX-12e achieved synthetic lethality indirectly by inhibiting EZH2 to increase the sensitivity to PARP1, and induced cell death by regulating excessive autophagy. KWLX-12e is expected to be a potential candidate for the treatment of TNBC.
研究领域:
肿瘤学
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药理学
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癌症生物学
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分子生物学
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DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2018
·
IF 6.042
Ke Yang,Xiang Yang,Xiang Zhao,Marc Lamy de la Chapelle,Weiling Fu
Simple, rapid, and efficient cell viability assays play a fundamental role in much of biomedical research, including cell toxicology investigations and antitumor drug screening. Here, we demonstrate for the first time a rapid and label-free cell viability assay using THz spectroscopy in combination with a new optical clearing agent (OCA) and microfluidic technology. This strategy uses a considerably less absorptive OCA to replace the highly absorptive water molecules around the living cells and thus to decrease the background signal interference. Three low-viscosity oils were screened as potential OCA candidates, among which fluorinated oil was selected because of its lower absorption and lowest cytotoxicity. After the liquid medium was replaced with fluorinated oil in a microfluidic chip, an obvious THz spectral difference was observed between the fluorinated oils with and without living cells. This change in THz response was preliminarily attributed to the distinguishable signals between the cells and the fluorinated oil. In addition, we applied this method to cell viability assays of human breast cancer cells (MDA-MB-231) after treatment with different antitumor drugs. The results indicated that THz spectroscopy with the aid of the proposed water-replacement strategy presented excellent quantification of cell viability with the advantages of a rapid, label-free, nondestructive microassay, which offers significant potential to developing a convenient and practical cell analysis platform.
研究领域:
生物医学工程
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细胞生物学
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药学
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产品关联
DOI
PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
·
2023
·Vol. 20
·期 4
·e202201203
·
IF 2.9
Weirong Song,Jie Zhang,Pengxiang Zhao,Yongchun Huang,Shoude Zhang
A novel monoterpene alkaloid, named incarvine G, was isolated from the Incarvillea sinensis Lam. Its chemical structure was elucidated using comprehensive spectroscopic methods. Incarvine G is an ester compound comprised of a monoterpene alkaloid and glucose. This compound showed evident inhibition on cell migration, invasion, and cytoskeleton formation of human MDA-MB-231 with low cytotoxicity.
研究领域:
药用植物学
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癌症研究
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化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MEDICINAL CHEMISTRY RESEARCH
·
2022
·Vol. 31
·期 6
·936-948
·
IF 2.351
Hu Shijia,Li Yunqi,Kan Weiqiong,Ding Tingting,Gu Haijun,Zhang Ting,Yi Zhengfang,Chen Yihua
A series of diphenyl- N -heteroaromatic compounds were designed, synthesized, and evaluated for anticancer efficacies (antimigration and antiproliferation) against human cancer cell lines. The favorable 2 H -1,2,3-triazole compound 4a was optimized, leading to the discovery of compounds 4b and 4c with more potent antimigratory and antiproliferative activities. The transwell assay showed that compounds 4b and 4c dose-independently inhibited the migration of the two cancer cell lines (human breast cancer cell line MDA-MB-231 and pancreatic cancer cell line PANC1) with the low IC 50 values of 0.24 and 0.47 µM, respectively. The sulforhodamine-B (SRB) assay showed that compounds 4b and 4c inhibited the proliferation of PANC1 cells with the IC 50 values 0.86 µM and 1.41 µM, respectively. These results indicate that compounds 4b and 4c with 1,2,3-triazole scaffold may be further developed as potent anticancer agents in the future.
A series of novel diphenyl- N -heteroaromatics based on our previous published research work were synthesized and evaluated for their antimigration efficacies against MDA-MB-231 and PANC1 human cancer cell lines. Compound 4c dose-independently inhibited the migration of the two cancer cell lines (MDA-MB-231 and PANC1) with low IC 50 values 0.32 µM and 0.24 µM respectively.
研究领域:
药理学
·
肿瘤学
·
有机化学
✓ 已验证
DOI
高影响因子
ONCOLOGY REPORTS
·
2020
·Vol. 44
·期 5
·2231-2240
·
IF 3.417
Jinhong Feng,Ting Zheng,Zhaohua Hou,Cui Lv,Anqi Xue,Tingting Han,Beibei Han,Xin Sun,Yunbo Wei
Estrogen receptor (ER)‑negative breast tumors are associated with low survival rates, which is related to their ability to grow and metastasize into distal organs. The aryl hydrocarbon receptor (AhR), a ligand‑activated transcription factor that is involved in several biological processes, is a promising anti‑metastatic target. Luteolin, a non‑toxic naturally occurring plant flavonoid with diverse biological activities, has been demonstrated to be effective against certain types of cancer, and has also been described as a ligand of AhR. In the present study, various cancer cell lines were first investigated following treatment with luteolin, and luteolin exhibited the lowest IC50 in MDA‑MB‑231 cells. Then, the efficiency of luteolin in suppressing the metastasis of ER‑negative breast cancer in vitro was assessed. MDA‑MB‑231 cells were treated with luteolin in vitro. Subsequently, MTT assay and flow cytometry were used to detect cell viability, the cell cycle and apoptosis, and a Transwell assay was used to evaluate cell invasion. In addition, reverse transcription‑semi‑quantitative PCR and western blot were performed to detect the mRNA and protein expression levels of matrix metalloproteinase (MMP)‑2 and MMP‑9. In addition, the number of surface tumor nodules was measured in vivo, in mice bearing B16‑F10 tumors, following treatment with luteolin. Luteolin inhibited the viability and induced the apoptosis of MDA‑MB‑231 cells, which was accompanied by cell cycle arrest. This was associated with a decrease in the expression of the pro‑metastatic markers C‑X‑C chemokine receptor type 4 (CXCR4), MMP‑2 and MMP‑9, which was reversed by AhR inhibition. Furthermore, it was identified that luteolin could inhibit the metastasis in a B16F10 mouse xenograft model, and the levels of MMP‑9, MMP‑2 and CXCR4 were significantly decreased in the lung tissues isolated from tumor‑bearing nude mice following luteolin treatment. In conclusion, luteolin is a potential molecule for inhibiting breast cancer invasion and metastasis, which could have promising clinical applications.
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
JOURNAL OF HAZARDOUS MATERIALS
·
2022
·
IF 14.224
Wenqi Diao,Jin Yan,Xuedong Wang,Qiuhui Qian,Huili Wang
Although triclosan (TCS) is ubiquitously detected in environmental media and organisms, little information is available on its cardiotoxicity and underlying mechanisms. Herein, acute TCS exposure (0.69–1.73 μM) to zebrafish from embryos (6 hpf) to larvae (72 hpf) resulted in cardiac development defects, including increased angle between atrium and ventricle, prolonged SV-BA distance, linearized heart and pericardial cyst in 72-hpf larvae. These malformations resulted from interfered oxidative-stress pathways, reflecting in accumulated ROS and MDA and inhibited SOD and CAT activities. By RT-qPCR, the transcription levels of four cardiac development-related marker genes were significantly up-regulated except for gata4 . Besides, miR-144 was identified as a regulatory molecule of TCS-induced cardiac defects by integrating analyses of artificial intervene expression and RNA-Seq data. Interestingly, the target genes of miR-144 were found and interacted with the above marker genes through constructing protein-protein interaction networks. After intervening the expression of miR-144 by microinjecting and activating Wnt pathway by an agonist BML-284, we confirmed that up-regulated miR-144 suppressed the expression of angiogenesis-related genes and negatively regulated Wnt pathway, further triggering angiogenesis disorders and cardiac phenotypic malformation. These findings unravel the underlying molecular mechanisms regarding TCS-induced cardiac development toxicity, and contribute to early warning and risk management of TCS.
研究领域:
毒理学
·
分子生物学
·
发育生物学
·
环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2023
·
IF 5.2
Guo Huanyu,Chen Jing,Yuan Xuemei,Zhang Jian,Wang Jiayang,Yao Jiayun,Ge Haixia
Herbal extracts have been considered as ideal alternative to antibiotics in aquaculture and application of combinatory effective extracts always can exhibit the enhanced bioactivity with high efficiency. In our study, a novel herbal extract combination GF-7, which is composed of Galla Chinensis, Mangosteen Shell extracts as well as the effective parts of Pomegranate peel and Scutellaria baicalensis Georgi extracts, was prepared and applied for the therapy of bacterial infection in aquaculture. The HPLC analysis of GF-7 was also investigated for quality control and chemical identification. In the bioassay, GF-7 had excellent antibacterial activity against various aquatic pathogenic bacteria in vitro, and the related MIC values were between 0.045 and 0.36 mg/mL. After feeding Micropterus salmoide with GF-7 (0.1, 0.3, and 0.6%, respectively) for 28 days, the activities of ACP, AKP, LZM, SOD, and CAT of the liver in each treatment group were significantly increased and the content of MDA was significantly decreased. Meanwhile, the hepatic expression of the immune regulators including IL-1β, TNF-α, and Myd88 at different times was up-regulated in varying degrees. The challenge results exhibited a good dose-dependent protective effect on M. salmoides infected with A. hydrophila, which was further confirmed by liver histopathology. Our results imply that the novel combination GF-7 is a potential natural medicine for the prevention and treatment of numerous aquatic pathogenic infectious diseases in aquaculture.
研究领域:
水产养殖
·
药理学
·
免疫学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Results in Chemistry
·
2025
·
IF 4.2
Basharat Ali,Muhammad Riaz,Ajmal Khan,Nadir Rasheed,Muhammad Masood,Ali Iftikhar,Amir Faisal,Sobia Ahsan Halim,Jalal Uddin,Afnan Jan,Ahmed Al-Harrasi
Carbothioamides exhibit many biological properties, including antiviral, antibacterial and anticancer activities. Their ability to interfere with DNA synthesis is mainly responsible for their anticancer activities. Here, twelve phenyl-substituted carbothioamides ( 2−13 ) were synthesized and characterized using Electron Ionization Mass Spectrometry (EI-MS), proton and carbon-13 nuclear magnetic resonance ((Singhal et al., 2013 [ 1 ] ) HNMR, and 13 C NMR), Infrared (IR), and elemental analysis. The anticancer activity of the carbothioamide derivatives ( 2–13 ) was measured in the HCT116 colorectal cancer cell line by means of a three day sulforhodamine B (SRB) proliferation assay. Among the series, four compounds ( 2 , 4 , 11 , and 12 ) which inhibited the cell viability by more than 50 % at 50 μM concentration. IC 50 determination of these four compounds revealed 1-benzoyl-4-(2-bromophenyl) thiosemicarbazide ( 11 ) as the most potent compound with IC 50 values of 21.61 ± 4.77 μM, 18.34 ± 3.53 μM and 17.87 ± 12.02 μM in the breast cancer (MCF-7) cell line, human colorectal carcinoma (HCT116) cell line and MD Anderson-metastatic breast (MDA-MB-453) cell lines respectively. Prolonged treatment of cells with the compound resulted in apoptotic cell death as determined by cleavage of Poly (ADP-ribose) polymerase (PARP), a caspase 3 substrate and an apoptotic marker. This study, therefore, explored novel derivatives of carbothioamides for their anticancer activities; the structure activity relationship (SAR) reported in this study and predicted docking analysis and ADMET profile will help optimize carbothioamides as anticancer agents.
研究领域:
药物化学
·
药理学
·
肿瘤学
·
生物化学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）