ONCOLOGY REPORTS
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2015
·Vol. 34
·期 3
·1115-1120
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IF 2.301
Bing-Jie Han,Wei Li,Guang-Bin Jiang,Shang-Hai Lai,Cheng Zhang,Chuan-Chuan Zeng,Yun-Jun Liu
In the present study, the in vitro cytotoxicity of daidzein was evaluated in human BEL-7402, A549, HeLa, HepG-2 and MG-63 cancer cell lines. BEL-7402 cells were sensitive to daidzein treatment, with an IC50 value of 59.7±8.1 µM. Daidzein showed no cytotoxic activity toward A549, HeLa, HepG-2 and MG-63 cells. Daidzein increased the levels of reactive oxygen species (ROS) and induced a decrease in mitochondrial membrane potential. Morphological and comet assays showed that daidzein effectively induced apoptosis in BEL-7402 cells. Additionally, daidzein caused cell cycle arrest at the G2/M phase in the BEL-7402 cell line. Daidzein downregulated the expression of Bcl-2, Bcl-x and Baid proteins and upregulated the levels of Bim protein in the BEL-7402 cells. The results demonstrated that daidzein induced BEL-7402 cell apoptosis through an ROS-mediated mitochondrial dysfunction pathway.
研究领域:
肿瘤学
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细胞生物学
·
药理学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2019
·Vol. 20
·期 19
·4803
·
IF 4.183
Shan Jin,Kuan Shi,Liu Liu,Yu Chen,Guangzhong Yang
Xanthones are important chemical constituents ofGarcinia xanthochymusand varied bioactivities including cytotoxicity. However, their anti-tumor mechanism has remained unknown. Here, we isolated and identified a new xanthone named garciniaxanthone I (1) and five known compounds from the bark ofG. xanthochymus. Their structures were elucidated by NMR analysis and HRESIMS. The anti-proliferation activities of all isolated compounds were evaluated on four human tumor cell lines (HepG2, A549, SGC7901, MCF-7). The results demonstrated that the anti-proliferation activity of xanthone was related to the number and location of prenyl groups. We further found that garciniaxanthone I (GXI) could induce HepG2 apoptosis and enhance the expression of cleaved caspase-8, caspase-9, and caspase-3. GXI could also increase Bax level and concurrently reduce the overexpression of Bcl-2, Bcl-XL, Mcl-1, and surviving in HepG2 cells. Moreover, GXI could inhibit cell migration of HepG2 cells by inhibiting the expressions of MMP-7 and MMP-9. In summary, our study suggests that GXI could induce HepG2 apoptosis via the mitochondrial pathway and might become a lead compound for liver cancer treatment.Keywords:xanthones;Garcinia xanthochymus;apoptosis;HepG2;caspase;Bcl-2 family;MMPs
研究领域:
药理学
·
肿瘤学
·
细胞生物学
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DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2022
·
IF 4.601
Guizhen Liu,Yanan Du,Tao Fu,Ying Han,Lifeng Pan,Jingwu Kang
An approach for profiling protein-protein interactions by using affinity purification with capillary monolithic immobilized metal affinity chromatography column (cm-IMAC) in combination with label free quantitative proteomics was described in the present work. The cm-IMAC columns were prepared in a single step by copolymerization of the function monomer , namely ( S )-2,2′-((1-carboxy-5-(pent‑4-enamido)pentyl)azanediyl)diacetic acid which provide a nitrilotriacetate (NTA) moiety to form chelated complexation with Ni (II) ions, inside the fused silica capillaries. The His 6 -tagged bait protein can be easily immobilized on the cm-IMAC columns through the formation of chelating complexation with the NTA-Ni (II) functional groups of the matrix. The cm-IMAC columns were used to explore protein-protein interactions (PPIs) on a proteomic scale when combined with label-free proteomics. A known interaction pair of proteins, namely NDP52 (amino acid sequence 10–126) and NAP1 (33–75) as well as Bcl-2 family proteins were used for proof of concept. New interactors of Bcl-X L were identified and validated by co-immunoprecipitation.
研究领域:
生物化学
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蛋白质组学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Chemical Neuroscience
·
2020
·
IF 4.486
Ruiqi Huang,Yanjing Zhu,Lijuan Lin,Simin Song,Liming Cheng,Rongrong Zhu
Oxidative stress of neurons caused by a series of complex neuropathological processes will induce certain neurodegenerative disorders including epilepsy. Curcumin (Cur) is an effective natural antioxidant compound; however, the poor bioavailability obstructs its neural protective applications. In this study, Cur is encapsulated in solid lipid nanoparticles (SLNs) for better neuroprotective efficacy. In vitro study certified that Cur-SLNs functioned obviously better against neuronal apoptosis than Cur, by significantly decreasing the level of free radical and reversing mitochondrial function through the activation of the Bcl-2 family. In vivo experiments showed that SLNs transported Cur through the blood–brain barrier (BBB). The behavioral performance of epileptic mice was improved by Cur-SLNs, with more NeuN but less TUNEL positive cells observed in hippocampus. The in vivo mechanism was also explored. Cur-SLNs reduced neuronal apoptosis through Bcl2 family and P38 MAPK pathways. Overall, Cur-SLNs have better protective effects toward oxidative stress in neurons than free Cur both in vitro and in vivo, which suggests they may be a promising agent against neurodegenerative disorders including epilepsy.
研究领域:
药理学
·
神经科学
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纳米技术
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Zhemeng Zhao,Bin Hu,Danfeng Zhang,Xinyue Cui,Wen Ding,Tongshuai Wang,Jingyi Wang,Ziyi Guo,Yingtang Zhou,Shige Wang,Jiaming Guo
Ionizing radiation (IR) injuries are featured as acute radiation syndrome (ARS) and localized combined radiation-wound injury (CRWI). While scavenging reactive oxygen species (ROS) is a key strategy for mitigating IR-induced damage, the development of effective marine natural biomaterials for treatment remains rare and challenging. In this study, we engineered cuttlefish melanin nanoparticles (CMNs) and incorporated them into a poly (vinyl alcohol) (PVA) and sodium alginate (SA) matrix, enabling the in situ synthesis of PVA/SA@CMNs (PS@CMNs) hydrogels with multifaceted therapeutic benefits. CMNs pretreatment significantly alleviated radiation-induced damage in ARS models, particularly by protecting the hematopoietic and immune systems. Furthermore, PS@CMNs hydrogels exhibited exceptional antioxidant, photothermal antibacterial, and biodegradable properties than CMNs. Upon near-infrared laser irradiation, these hydrogels accelerated the healing of bacteria-infected CRWI. The therapeutic mechanism involves the regulation of apoptosis-related proteins, including Bax and Bcl-2, effectively inhibiting the apoptotic process. This study highlights the dual-action potential of CMNs and PS@CMNs hydrogels in mitigating radiation damage and promoting wound healing, offering a promising marine biomaterial-based approach for radiation protection and regenerative medicine.
研究领域:
放射生物学
·
生物材料学
·
再生医学
✓ 已验证
产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2018
·
IF 4.816
Yong-Yu Qi,Qian Gan,Ya-Xian Liu,Ya-Hong Xiong,Zong-Wan Mao,Xue-Yi Le
In the search for more effective anticancer drugs with less toxic side effects, dipeptides were introduced into the Cu(II) complex of 5-methyl-2-(2′-pyridyl)benzimidazole (HPBM). Analytical and spectroscopic techniques were employed to thoroughly characterize complexes [Cu(Gly-gly)(HPBM)(H 2 O)]ClO 4 ·0.5H 2 O ( 1 ) and [Cu(Gly- L -leu)(HPBM)(H 2 O)]ClO 4 ( 2 ) (where Gly-gly = Glycyl-glycine anion, Gly- L -leu = Glycyl- l -leucine anion). The solution stability studies performed by ultraviolet–visible (UV–Vis) spectroscopy confirmed the stability of the complexes in the buffer solutions. The DNA binding affinity was evaluated using multi-spectroscopy, viscosity measurement and molecular docking methods and further quantified by K b and K app values, revealing an intercalative mode. Moreover, gel electrophoresis analysis revealed that the complexes could damage CT DNA through a hydroxyl radical pathway in the presence of ascorbic acid . All the complexes displayed favorable antimicrobial and cytotoxic activities toward the tested microorganisms ( Bacillus subtilis , Staphylococcus aureus , Escherichia coli and Pseudomonas aeruginosa ) and cancer cells (A549, HeLa and PC-3). Most importantly, the possible anticancer mechanism of the complexes was explored by determining the cells morphological changes, intracellular reactive oxygen species (ROS) levels, location in mitochondria, mitochondrial membrane potentials and the expression of Bcl-2 family proteins. The results showed that the complexes could induce apoptosis in HeLa cells through an ROS-mediated mitochondrial dysfunction pathway, which was accompanied by the regulation of Bcl-2 family proteins.
研究领域:
化学
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药理学
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分子生物学
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癌症研究
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微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL BIOCHEMISTRY AND BIOPHYSICS
·
2014
·Vol. 71
·期 3
·1349-1356
·
IF 2.38
Jin Di,Cao Ming,Mu Xin,Yang Guoliang,Xue Wei,Huang Yiran,Chen Haige
Catalpol is an iridoid glucoside extracted from the traditional Chinese medicinal plant called Rehmannia glutinosa , and it is reported to possess a variety of pharmacological activities. The goal of this research was to explore the effect of catalpol on the human bladder cancer cells T24. The cells were treated for different durations with various concentrations of catalpol. Then the viability, mobility, and invasiveness of the cells were determined by MTT assay and flow cytometry, respectively. Catalpol was found to significantly suppress the proliferation, migration, and invasiveness of T24 bladder cancer cells in a dose- and time-dependent manner. The results also revealed that catalpol promoted apoptosis and caused the cell-cycle arrest at G2/M phase. Furthermore, the catalpol-mediated apoptosis was found to involve the modulation of PI3K/Akt pathway and inhibit the expression of anti-apoptotic B cell lymphoma-2 (Bcl-2) family proteins. Also, the expressions of Bcl-2 proapoptotic effectors, Bcl-2-associated X protein, and Bcl-2 associated death promoter were up-regulated in the cells treated with catalpol. The enzymes involved in the ultimate process of apoptosis, active caspase-3 and poly ADP ribose polymerase were elevated, and the latter was observed to be cleaved, indicating that catalpol-accelerated cell apoptosis involved a caspase-dependent pathway. These results suggest that catalpol might serve to be a promising therapeutic agent for the treatment of human bladder cancer.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Yanan Wang,Huichao Wei,Keyang Li,Liru Liu,Yingfei Zhu,Xinyuan Wang,Jiahui Yan,Liangmin Yu,Xuefeng Yan,Zhiyu He
Calcium overload in hepatocytes mediates the crosstalk and amplification loop with oxidative stress and severe inflammation that initiate pro-apoptotic and necrotic signaling pathways in acute liver injury (ALI). In this study, an N-acetylgalactosamine-modified amphiphilic dextran-silibinin conjugate (GalNAc-Dex-Sil) with ROS-sensitive phenylboronic acid (PBA) linkage was synthesized. The as-prepared amphiphilic polymer was self-assembled into GalNAc-Dex-Sil nanoparticles, which efficiently encapsulated the membrane-permeable calcium chelator BAPTA-AM (BA), achieving GalNAc-mediated hepatocyte-specific targeting and ROS-responsive release in injured hepatocytes through PBA cleavage. Accordingly, a single low-dose injection of formulation (BA: 150 μg·kg −1 ) significantly alleviated hepatocyte oxidative stress and inflammation, rescued dying hepatocytes, prevented further hepatocyte damage, and ultimately restored liver function in the ALI mouse model by 1) rapidly and effectively eliminating the overloaded calcium and scavenging excessive ROS via released BA to block the feed-forward vicious cycles of the cell damage, 2) inhibiting the inflammatory cascade by decreasing the expression of the key factor of the NF-κB/NLPR3 axis, 3) inhibiting the key branch of the mitochondrial apoptotic pathway (Cyt C/Bcl-2 family/caspase-3 axis) and death receptor pathway (TNFα/Caspase-8 axis), and 4) stabilizing hepatocyte membranes through the synergistic hepatoprotective effect of silibinin. Taken together, this formulation exhibited great potential as a potent and effective ALI treatment strategy.
研究领域:
药理学
·
纳米技术
·
肝病学
·
炎症
·
细胞凋亡
✓ 已验证
产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6
Juan Feng,Yidong Liu,Xia Tian,Chen Shen,Zhiqiang Feng,Jingxu Zhang,Xiangli Yao,Meilin Pu,Xuguang Miao,Lan Ma,Shouxin Liu
Steroid hybrids have emerged as a type of advantageous compound as they could offer improved pharmacological and pharmaceutical properties. Here, we report a series of novel peptide–dehydroepiandrosterone hybrids, which would effectively induce endoplasmic reticulum stress (ERS) and lead to apoptosis with outstanding in vitro and in vivo anti-melanoma effects. The lead compound IId among various steroids conjugated with peptides and pyridines showed effective in vivo activity in B16 xenograft mice: in medium- and high-dose treatment groups (60 and 80 mg/kg), compound IId would significantly inhibit the growth of tumours by 98%–99% compared to the control group, with the highest survival rate as well. Further mechanism studies showed that compound IId would damage the endoplasmic reticulum and upregulate the ERS markers C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (GRP78), which could further regulate caspase and Bcl-2 family proteins and lead to cell apoptosis. The compound IId was also proven to be effective in inhibiting B16 cell migration and invasion.
研究领域:
药理学
·
肿瘤学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
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