Scientific Reports
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2025
·Vol. 15
·期 1
·1-14
·
IF 3.9
Yue Qiulin,Liu Yongxuan,Li Fujia,Hong Tao,Guo Shousen,Cai Mengrui,Zhao Lin,Su Le,Zhang Song,Zhao Chen,Li Kunlun
Fucoidan is a fucose-rich sulfated polysaccharide that has gained attention owing to its various biological activities. In this study, fucoidan was isolated from Saccharina japonica using an enzyme-assisted method, and its antioxidant and anti-hepatocarcinoma effects were evaluated. The fucoidan was a 112.8 kDa polysaccharide comprising seven monosaccharides: fucose, xylose, glucuronic acid, rhamnose, glucose, mannose, and galactose. The main chain residues were (1 → 3)-α-L-Fuc p and (1 → 4)-α-L-Fuc p units with sulfate groups at the C-2/C-4 positions of the (1 → 3)-α-L-Fuc p residues. S. japonica fucoidans showed excellent antioxidant potency with values of 1.02 mg TE/g and 5.39 mg TE/g for the ABTS and FRAP assays, respectively. Additionally, they exerted antitumor efficacy and low systemic toxicity in H22 tumor-bearing mice, with a tumor inhibition rate of 42.93%. Furthermore, it significantly inhibited tumor angiogenesis and reduced pro-inflammatory cytokines levels (IL-1β, IL-6, and TNF-α). Our results suggest that fucoidan isolated from S. japonica possesses potent antioxidant and anticancer properties and may be used as a potential agent for hepatocellular carcinoma treatment.
研究领域:
海洋生物学
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药理学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
·
2025
·
IF 2.5
Xiaoliang Zhao,Yanmei Liu,Haili Wang,Kaili Qi,Haidong Wen,Yuxin Wang,Yuanyuan Ma,Cunjin Wang,Jing Zhang,Yonggang Wang,Weijie Zhang
In this study, three polysaccharides (RHC, RHH, and RHA) were sequentially extracted from Rheum officinale Baill., under different conditions, and their sulfated, phosphorylated, and selenated derivatives were successfully synthesized. Results indicated that the sequential extraction method effectively separated polysaccharides with distinct structures. According to their charge properties, these three polysaccharides were identified as acidic polysaccharides with different structural characteristics. Activity assays showed that the phosphorylation modification of polysaccharides significantly enhanced the scavenging of hydroxyl, superoxide, and DPPH radicals, as well as the inhibitory effects on HepG2 and HeLa cells. Phosphorylated derivatives also promoted proliferation, phagocytosis, and nitric oxide (NO) release in RAW264.7 macrophages. In the 50–800 µg/mL range, these polysaccharides and their derivatives exhibited no cytotoxicity to RAW264.7 cells and significantly promoted cell proliferation, phagocytosis, and NO release. Notably, RHC and its derivatives have the most prominent antitumor and immunomodulatory effects. Overall, R. officinale polysaccharides and their derivatives, especially phosphorylated ones, have potential applications in health food and pharmaceuticals. Graphical
研究领域:
药理学
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植物化学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2024
·
IF 4.5
Xiaomeng Lu,Xinyu Zhan,Guozi Xia,Feifei Wang,Mingjia Lv,Renwei Liu,Yuxue Liu,Chen Zi,Guangyong Li,Rui Wang,Jun Li,Fengjiao Yuan,Dianlong Jia
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an attractive candidate for anticancer therapeutics due to its efficient pro-apoptotic activity against tumor cells and its well-tolerated safety profile. However, the in vivo antitumor efficacy of TRAIL is often limited by its poor tumor targeting capacity. Nowadays, the B7 homologue 3 (B7–H3) immune checkpoint has emerged as a promising target for tumor immunotherapy and drug delivery. Here, we report the achievement of tumor-targeted delivery of TRAIL by genetically fusing it with a B7H3-antagonistic affibody. The affibody–TRAIL fusion protein, named ACT, was easily expressed in Escherichia coli with a high yield and could form the active trimeric state. In vitro ACT showed significantly increased cellular binding to multiple B7H3-positive tumor cells and improved cytotoxicity by 2–3 times compared to the parent TRAIL. In vivo ACT demonstrated a 2.4-fold higher tumor uptake than TRAIL in mice bearing B7H3-positive A431 tumor grafts. More importantly, ACT exhibited significantly improved antitumor efficacy against tumors in vivo. In addition, ACT treatment did not cause body weight loss or histopathological changes in the major organs of mice, indicating its good safety profile. Overall, our findings demonstrate that targeting B7H3 to enhance TRAIL delivery is a viable approach to improve its therapeutic efficacy, and ACT may be a potential agent for targeted therapy of B7H3-positive tumors.
研究领域:
肿瘤学
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免疫治疗
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Yongping He,Qianxue Yu,Xiaoyu Ma,Diya Lv,Hui Wang,Weian Qiu,Xiao fei Chen,Yang Jiao,Yue Liu
Ethnopharmacological relevance Tanacetum parthenium (L.) Schultz-Bip, commonly known as feverfew, has been traditionally used to treat fever, migraines, rheumatoid arthritis, and cancer. Parthenolide (PTL), the main bioactive ingredient isolated from the shoots of feverfew, is a sesquiterpene lactone with anti-inflammatory and antitumor properties. Previous studies showed that PTL exerts anticancer activity in various cancers, including hepatoma, cholangiocarcinoma, acute myeloid leukemia, breast, prostate, and colorectal cancer. However, the metabolic mechanism underlying the anticancer effect of PTL remains poorly understood. Aim of the study To explore the anticancer activity and underlying mechanism of PTL in human cholangiocarcinoma cells. Material and methods In this investigation, the effects and mechanisms of PTL on human cholangiocarcinoma cells were investigated via a liquid chromatography/mass spectrometry (LC/MS)-based metabolomics approach. First, cell proliferation and apoptosis were evaluated using cell counting kit-8 (CCK-8), flow cytometry analysis, and western blotting. Then, LC/MS-based metabolic profiling along with orthogonal partial least-squares discriminant analysis (OPLS-DA) has been constructed to distinguish the metabolic changes between the negative control group and the PTL-treated group in TFK1 cells. Next, enzyme-linked immunosorbent assay (ELISA) was applied to investigate the changes of metabolic enzymes associated with significantly alerted metabolites. Finally, the metabolic network related to key metabolic enzymes, metabolites, and metabolic pathways was established using MetaboAnalyst 5.0 and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway Database. Results PTL treatment could induce the proliferation inhibition and apoptosis of TFK1 in a concentration-dependent manner. Forty-three potential biomarkers associated with the antitumor effect of PTL were identified, which primarily related to glutamine and glutamate metabolism, alanine, aspartate and glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, arginine biosynthesis, arginine and proline metabolism, glutathione metabolism, nicotinate and nicotinamide metabolism, pyrimidine metabolism, fatty acid metabolism, phospholipid catabolism, and sphingolipid metabolism. Pathway analysis of upstream and downstream metabolites, we found three key metabolic enzymes, including glutaminase (GLS), γ-glutamyl transpeptidase (GGT), and carnitine palmitoyltransferase 1 (CPT1), which mainly involved in glutamine and glutamate metabolism, glutathione metabolism, and fatty acid metabolism. The changes of metabolic enzymes associated with significantly alerted metabolites were consistent with the levels of metabolites, and the metabolic network related to key metabolic enzymes, metabolites, and metabolic pathways was established. PTL may exert its antitumor effect against cholangiocarcinoma by disturbing metabolic pathways. Furthermore, we selected two positive control agents that are considered as first-line chemotherapy standards in cholangiocarcinoma therapy to verify the reliability and accuracy of our metabolomic study on PTL. Conclusion This research enhanced our comprehension of the metabolic profiling and mechanism of PTL treatment on cholangiocarcinoma cells, which provided some references for further research into the anti-cancer mechanisms of other drugs.
研究领域:
药理学
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肿瘤学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2017
·
IF 3.671
Jun Wu,Weiping Gao,Zhuoyue Song,Qingping Xiong,Yingtao Xu,Yun Han,Jun Yuan,Rong Zhang,Yunbo Cheng,Jiansong Fang,Weirong Li,Qi Wang
The purpose of this study was to investigate the anticancer activity of polysaccharide (PGL) from Glehnia littoralis on human lung cancer cell line A549. Based on MTT assay, the results suggested that PGL could significantly reduce A549 cells proliferation in a time- and dose-dependent manner. In addition, PGL displayed an inhibitory activity for the A549 cells migration in Transwell migration assay. The results from both flow cytometry analysis and Hochst 3342 staining of apoptotic cells indicated that PGL could promote apoptosis, and induce cycle arrest of A549 cells. Moreover, immunofluorescence assay elucidated PGL could also down-regulate expression of proliferating cell nuclear antigen (PCNA). Overall, these results showed that PGL exerts a strong anticancer action through inhibiting the A549 cells migration, proliferation and inducing cell apoptosis. It could be a new source of natural anticancer agent against lung cancer with potential value in supplements and medicine.
研究领域:
药理学
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肿瘤学
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植物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
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2020
·
IF 4.831
Shiyang Zhou,Gangliang Huang
In this study, a series of novel 7 H -benzo [ c ] [1,3] dioxolo [4, 5- f ] chromen-7-one derivatives were obtained by structural modification of the lead compounds with Fissitungfine B. A total 15 compounds were designed, synthesized and evaluated as inhibitors of tumor. These target compounds have the novel chemical structures that named three six-membered rings including one lactone six-membered ring. In vitro assay, the results showed that the target compounds have a broad spectrum and strong of anti-tumor activity. Such as the target compound 4n to MCF-7 was IC 50 = 0.35 ± 0.01 μM, to A-549 was IC 50 = 0.37 ± 0.01 μM, to Hela was IC 50 = 0.56 ± 0.02 μM, to MDC-803 was IC 50 = 0.53 ± 0.02 μM and COLO-205 was IC 50 = 0.50 ± 0.02 μM in vitro . At the same time, in vivo anti-tumor activity assay results showed that the target compounds had a good inhibitory effect on tumor growth. Among them, the target compound 4n had the best anti-tumor activity, it could inhibit tumor growth well at a low dose. The target compound 4n could be used as a candidate drug for further research and development, in order to be used as early as application in the clinical treatment of tumors.
研究领域:
药物化学
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肿瘤学
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有机合成
✓ 已验证
DOI
PubMed
高影响因子
MOLECULES
·
2024
·Vol. 29
·期 17
·4001
·
IF 4.2
Sijia Wang,Huifang Xu,Yuanyuan Li,Lingyi Zhang,Shouhong Xu
Stimulus-responsive materials hold significant promise for antitumor applications due to their variable structures and physical properties. In this paper, a series of peptides with a responsive viologen derivative, Pep-CnV (n= 1, 2, 3) were designed and synthesized. The process and mechanism of the interaction were studied and discussed. An ultraviolet–visible (UV) spectrophotometer and fluorescence spectrophotometer were used to study their redox responsiveness. Additionally, their secondary structures were measured by Circular Dichroism (CD) in the presence or absence of the reductant, Na2SO3. DPPC and DPPG liposomes were prepared to mimic normal and tumor cell membranes. The interaction between Pep-CnV and biomembranes was investigated by the measurements of surface tension and cargo leakage. Results proved Pep-CnV was more likely to interact with the DPPG liposome and destroy its biomembrane under the stimulus of the reductant. And the destruction increased with the length of the hydrophobic tail chain. Pep-CnV showed its potential as an intelligent antitumor agent.
研究领域:
生物化学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2015
·Vol. 20
·期 2
·2034-2060
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IF 2.416
Chang-Wei Li,Hua-Jin Dong,Cheng-Bin Cui
Twelve galloyl glucosides1–12, showing diverse substitution patterns with two or three galloyl groups, were synthesized using commercially available, low-costd-glucose and gallic acid as starting materials. Among them, three compounds, methyl 3,6-di-O-galloyl-α-d-glucopyranoside (9), ethyl 2,3-di-O-galloyl-α-d-glucopyranoside (11) and ethyl 2,3-di-O-galloyl-β-d-glucopyranoside (12), are new compounds and other six, 1,6-di-O-galloyl-β-d-glucopyranose (1), 1,4,6-tri-O-galloyl-β-d-glucopyranose (2), 1,2-di-O-galloyl-β-d-glucopyranose (3), 1,3-di-O-galloyl-β-d-glucopyranose (4), 1,2,3-tri-O-galloyl-α-d-glucopyranose (6) and methyl 3,4,6-tri-O-galloyl-α-d-glucopyranoside (10), were synthesized for the first time in the present study. Inin vitroMTT assay,1–12inhibited human cancer K562, HL-60 and HeLa cells with inhibition rates ranging from 64.2% to 92.9% at 100 μg/mL, and their IC50values were determined to be varied in 17.2–124.7 μM on the tested three human cancer cell lines. In addition, compounds1–12inhibited murine sarcoma S180 cells with inhibition rates ranging from 38.7% to 52.8% at 100 μg/mL in thein vitroMTT assay, andin vivoantitumor activity of1and2was also detected in murine sarcoma S180 tumor-bearing Kunming mice using taxol as positive control.Keywords:galloyl glucoside;synthesis;antitumor activity
研究领域:
有机化学
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药理学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Marine Drugs
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2022
·Vol. 20
·期 5
·284
·
IF 6.085
Yuting Zhu,Shanhao Han,Jianhui Li,Hongwei Gao,Bo Dong
Marine ascidian is becoming one of the main sources of an antitumor drug that has shown high bioactivity and extensive application in cancer treatment.Halocynthia roretzi, an edible marine sea squirt, has been demonstrated to have various kinds of biological activities, such as anti-diabetic, anti-hypertension, and enhancing immunity. In this study, we reported that aqueous extracts from the edible parts ofH. roretzipresented significantly inhibiting the efficiency on HepG-2 cell viability. The separate mixed compound exhibited strong effects of inhibitory proliferation and induced apoptosis via the generation of ROS along with the concurrent loss of mitochondrial membrane potential on tumor cells. Furthermore, we found that there existed a significantly synergistic effect of the ascidian-extracted compound mixture with the anti-cancer drug doxorubicin. In the presence of the extracts fromH. roretzi, the dose of doxorubicin at the cellular level could be reduced by a half dose. The extracts were further divided by semipreparative-HPLC and the active ingredients were identified as a mixture of fatty amide, which was composed of hexadecanamide, stearamide, and erucamide by UHPLC-MS/MS. Our results suggest that the potential toxicity of ascidianH. roretziin tumor cells, and the compounds extracted fromH. roretzicould be potentially utilized on functional nutraceuticals or as an adjunct in combination with chemotherapy.Keywords:ascidian;Halocynthia roretzi;anti-tumor;drug combination;doxorubicin
研究领域:
海洋生物学
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肿瘤学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2017
·
IF 2.896
Jun Wang,Qiuwen Li,Xiaojuan Li,Weiqi Yuan,Sichao Huang,Shaohui Cai,Jun Xu
Fibroblast activation protein-α (FAPα) is a serine protease of the post-prolyl peptidase family that is specifically expressed in the majority of human epithelial tumors , but not in normal tissues. In this study, we demonstrated the anti-tumor activity of a novel targeting drug formed by conjugating epirubicin (EPI) with an FAPα-specific dipeptide (Z-Gly-Pro) and named it Z-GP-EPI. Consistent with this tumor-targeting delivery strategy, the results illustrated that Z-GP-EPI could release EPI efficiently after incubating with FAPα and could exhibit similar antitumor effects as EPI in vitro in FAPα over-expressed tumor cells (4T1/FAPα + ). Furthermore, the evaluation of antitumor activity of Z-GP-EPI in vivo was implemented in a 4T1/FAPα + tumor-bearing mice xenograft model. Our results illustrated that Z-GP-EPI had similar antitumor effects in 4T1/FAPα + tumor-bearing mice and showed no visible cardiotoxicity side effects compared with free EPI. Thus, our study indicated that this FAPα-activated prodrug targeting strategy may provide a new mechanism for the targeted delivery of antitumor agents and improve their safety levels.
研究领域:
肿瘤学
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药理学
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生物化学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR CELL
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2024
·
IF 14.5
Zhenxi Zhang,Yanting Yang,Yang Chen,Jingyu Su,Wenjing Du
The functional integrity of CD8 + T cells is closely linked to metabolic reprogramming; therefore, understanding the metabolic basis of CD8 + T cell activation and antitumor immunity could provide insights into tumor immunotherapy. Here, we report that ME2 is critical for mouse CD8 + T cell activation and immune response against malignancy. ME2 deficiency suppresses CD8 + T cell activation and anti-tumor immune response in vitro and in vivo . Mechanistically, ME2 depletion blocks the TCA cycle flux, leading to the accumulation of fumarate. Fumarate directly binds to DAPK1 and inhibits its activity by competing with ATP for binding. Notably, pharmacological inhibition of DAPK1 abolishes the anti-tumor function conferred by ME2 to CD8 + T cells. Collectively, these findings demonstrate a role for ME2 in the regulation of CD8 + T cell metabolism and effector functions as well as an unexpected function for fumarate as a metabolic signal in the inhibition of DAPK1.
研究领域:
免疫学
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肿瘤学
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代谢生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Advanced Research
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2022
·
IF 12.822
Bingling Zhong,Lin Zhao,Jie Yu,Ying Hou,Nana Ai,Jin-Jian Lu,Wei Ge,Xiuping Chen
Introduction The anti-cancer effect of high concentrations of ascorbic acid (AA) has been well established while its underlying mechanisms remain unclear. The association between iron and AA has attracted great attention but was still controversial due to the complicated roles of iron in tumors. Objectives Our study aims to explore the anti-cancer mechanisms of AA and the interaction between AA and iron in cancer. Methods The MTT and ATP assays were used to evaluate the cytotoxicity of AA. Reactive oxygen species (ROS) generation, calcium (Ca 2+ ), and lipid peroxidation were monitored with flow cytometry. Mitochondrial dysfunction was assessed by mitochondrial membrane potential (MMP) detection with JC-1 or tetramethylrhodamine methyl ester (TMRM) staining. Mitochondrial swelling was monitored with MitoTracker Green probe. FeSO 4 (Fe 2+ ), FeCl 3 (Fe 3+ ), Ferric ammonium citrate (Fe 3+ ), hemin chloride (Fe 3+ ) were used as an iron donor to investigate the effects of iron on AA’s anti-tumor activity. The in vivo effects of AA and iron were analyzed in xenograft zebrafish and allograft mouse models. Results High concentrations of AA exhibited cytotoxicity in a panel of cancer cells. AA triggered ROS-dependent non-apoptotic cell death. AA-induced cell death was essentially mediated by the accumulated intracellular Ca 2+ , which was partly originated from endoplasmic reticulum (ER). Surprisingly, exogenous iron could significantly reverse AA-induced ROS generation, Ca 2+ overloaded, and cell death. Especially, the iron supplements significantly impaired the in vivo anti-tumor activity of AA. Conclusions Our study elucidated the protective roles of iron in ROS/Ca 2+ mediated necrosis triggered by AA both in vitro and in vivo , which might shed novel insight into the anti-cancer mechanisms and provide clinical application strategies for AA in cancer treatment.
研究领域:
肿瘤学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
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