CHEMISTRY & BIODIVERSITY
·
2025
·
IF 2.5
Fuju Xu,Guangchun Liu,Chujie Zhao,Shenglin Zhang,Ruoyan Lin,Xudong Cao,Zonghe Yu,Peng Luo,Wen Huang,Lihong Yuan
This paper aimed to isolate and characterize the saponins from Holothuria leucospilota and investigate their potential antitumor effects and antitumor targets using network pharmacology and bioinformatics. The purified saponins were analyzed using electrospray ionization–tandem mass spectrometry (ESI–MS/MS). Ten saponins were identified. The in vitro experiments demonstrated that H. leucospilota saponins exhibited significant dose-dependent inhibition on HepG2, Panc02, and UM-UC-3 cell proliferation and differentiation. In addition, through network pharmacology, bioinformatics, and molecular docking, a total of 22 key tumor targets of H. leucospilota saponins were identified. Then, the reverse-transcription quantitative polymerase chain reaction (RT-qPCR) results showed that the saponins from H. leucospilota can inhibit the expression of target genes AURKB , BIRC5 , CHEK1 , PTGS2 , and MMP9 , and may affect the neuroactive ligand–receptor signaling pathway, thereby suppressing tumor proliferation and migration. In conclusion, we have demonstrated that the saponin extract from H. leucospilota has potential application value in tumor therapy. Graphical
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nutrients
·
2023
·Vol. 15
·期 2
·378
·
IF 5.9
Ruizhen Ru,Gengzhan Chen,Xiaoxia Liang,Xudong Cao,Lihong Yuan,Minjie Meng
Bladder cancer is a highly recurrent disease and a common cause of cancer-related deaths worldwide. Despite recent developments in diagnosis and therapy, the clinical outcome of bladder cancer remains poor; therefore, novel anti-bladder cancer drugs are urgently needed. Natural bioactive substances extracted from marine organisms such as sea cucumbers, scallops, and sea urchins are believed to have anti-cancer activity with high effectiveness and less toxicity. Frondoside A is a triterpenoid glycoside isolated from sea cucumber,Cucumaria frondosa. It has been demonstrated that Frondoside A exhibits anti-proliferative, anti-invasive, anti-angiogenic, anti-cancer, and potent immunomodulatory effects. In addition, CpG oligodeoxynucleotide (CpG-ODN) has also been shown to have potent anti-cancer effects in various tumors models, such as liver cancer, breast cancer, and bladder cancer. However, very few studies have investigated the effectiveness of Frondoside A against bladder cancer alone or in combination with CpG-ODN. In this study, we first investigated the individual effects of both Frondoside A and CpG-ODN and subsequently studied their combined effects on human bladder cancer cell viability, migration, apoptosis, and cell cycle in vitro, and on tumor growth in nude mice using human bladder cancer cell line UM-UC-3. To interrogate possible synergistic effects, combinations of different concentrations of the two drugs were used. Our data showed that Frondoside A decreased the viability of bladder cancer cells UM-UC-3 in a concentration-dependent manner, and its inhibitory effect on cell viability (2.5 μM) was superior to EPI (10 μM). We also showed that Frondoside A inhibited UM-UC-3 cell migration, affected the distribution of cell cycle and induced cell apoptosis in concentration-dependent manners, which effectively increased the sub-G1 (apoptotic) cell fraction. In addition, we also demonstrated that immunomodulator CpG-ODN could synergistically potentiate the inhibitory effects of Frondoside A on the proliferation and migration of human bladder cancer cell line UM-UC-3. In in vivo experiments, Frondoside A (800 μg/kg/day i.p. for 14 days) alone and in combination with CpG-ODN (1 mg/kg/dose i.p.) significantly decreased the growth of UM-UC-3 tumor xenografts, without any significant toxic side-effects; however, the chemotherapeutic agent EPI caused weight loss in nude mice. Taken together, these findings indicated that Frondoside A in combination with CpG-ODN is a promising therapeutic strategy for bladder cancer.Keywords:bladder cancer;Frondoside A;CpG oligodexynucleotides;cell viability;apoptosis;cell migration
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Oncology
·
2023
·
IF 4.7
Guangchun Liu,Shenglin Zhang,Ruoyan Lin,Xudong Cao,Lihong Yuan
Cancer remains the leading cause of death worldwide. In spite of significant advances in targeted and immunotherapeutic approaches, clinical outcomes for cancer remain poor. The aim of the present study was to investigate the potential mechanisms and therapeutic targets of Frondoside A for the treatment of liver, pancreatic, and bladder cancers. The data presented in our study demonstrated that Frondoside A reduced the viability and migration of HepG2, Panc02, and UM-UC-3 cancer cell in vitro . Moreover, we utilized the GEO database to screen and identify for differentially expressed genes (DEGs) in liver, pancreatic, and bladder cancers, which resulted in the identification of 714, 357, and 101 DEGs, respectively. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation were performed using the Metascape database for DEGs that were significantly associated with cancer development. The protein-protein interaction (PPI) networks of the identified DEGs in liver, pancreatic, and bladder cancers were analyzed using Cytoscape 3.9.0 software, and subsequently identified potential key genes that were associated with these networks. Subsequently, their prognostic values were assessed by gene expression level analysis and Kaplan-Meier survival analysis (GEPIA). Furthermore, we utilized TIMER 2.0 to investigate the correlation between the expression of the identified key gene and cancer immune infiltration. Finally, molecular docking simulations were performed to assess the affinity of Frondoside A and key genes. Our results showed a significant correlation between these DEGs and cancer progression. Combined, these analyses revealed that Frondoside A involves in the regulation of multiple pathways, such as drug metabolism, cell cycle in liver cancer by inhibiting the expression of CDK1, TOP2A, CDC20, and KIF20A, and regulates protein digestion and absorption, receptor interaction in pancreatic cancer by down-regulation of ASPM, TOP2A, DLGAP5, TPX2, KIF23, MELK, LAMA3, and ANLN. While in bladder cancer, Frondoside A regulates muscle contraction, complement and coagulation cascade by increase FLNC expression. In conclusion, the present study offers valuable insights into the molecular mechanism underlying the anticancer effects of Frondoside A, and suggests that Frondoside A can be used as a functional food supplement or further developed as a natural anti-cancer drug.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nutrients
·
2022
·Vol. 14
·期 4
·786
·
IF 6.706
Ruizhen Ru,Yanzheng Guo,Juanxuan Mao,Zonghe Yu,Wen Huang,Xudong Cao,Huijian Hu,Minjie Meng,Lihong Yuan
Cancer remains the primary cause of death worldwide. To develop less toxic anti-cancer drugs to relieve the suffering and improve the survival of cancer patients is the major focus in the anti-cancer field. To this end, marine creatures are being extensively studied for their anti-cancer effects, since extracts from at least 10% of the marine organisms have been shown to possess anti-tumor activities. As a classic Chinese traditional medicine, sea cucumbers and compounds extracted from the sea cucumbers, such as polysaccharides and saponins, have recently been shown to exhibit anti-cancer, anti-inflammatory, and anti-oxidant effects.Holothuria leucospilota(H. leucospilota) is a tropical edible sea cucumber species that has been successfully cultivated and farmed in large scales, providing a readily available source of raw materials to support the development of novel marine anti-cancer drugs. However, very few studies have so far been performed on the biological activities ofH. leucospilota. In this study, we first investigated the anti-cancer effect ofH. leucospilotaprotein on three cancer cell lines (i.e., HepG2, A549, Panc02) and three normal cell lines (NIH-3T3, HaCaT, 16HBE). Our data showed thatH. leucospilotaprotein decreased the cell viabilities of HepG2, A549, HaCaT, 16HBE in a concentration-dependent manner, while Panc02 and NIH-3T3 in a time- and concentration-dependent manner. We also found that the inhibitory effect ofH. leucospilotaprotein (≥10 μg/mL) on cell viability is near or even superior to EPI, a clinical chemotherapeutic agent. In addition, our data also demonstrated thatH. leucospilotaprotein significantly affected the cell cycle and induced apoptosis in the three cancer cell lines investigated; in comparison, it showed no effects on the normal cell lines (i.e., NIH-3T3, HaCaT and 16HBE). Finally, our results also showed thatH. leucospilotaprotein exhibited the excellent performance in inhibiting cell immigrations. In conclusion,H. leucospilotaprotein targeted the cancer cell cycles and induced cancer cell apoptosis; its superiority to inhibit cancer cell migration compared with EPI, shows the potential as a promising anti-cancer drug.Keywords:sea cucumber protein;anti-cancer activity;targeted effects;cell apoptosis;cell migration;marine extractions
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2021
·
IF 10.618
He Cheng,Langlang Yi,Jianduo Wu,Guoqian Li,Gang Zhao,Zhixiang Xiao,Bo Hu,Lei Zhao,Jie Tian
Drug detection in biofluids has always been great importance for clinical diagnosis. Many detection technologies such as chromatography-mass spectrometry, have been applied to the detection of drugs. However, these technologies required multi-step operations, including complicated and time-consuming pretreatment processes and operations of bulky detection instruments, significantly limiting development of drug detection in clinical diagnosis. Herein, a portable 3D-printed paper cartridge was fabricated for fast sample preconcentration and direct drugs quantitative detection in biofluids by a portable Raman spectrometer. This cartridge contained both paper tip with silver nanowires to preconcentrate samples and achieve surface-enhanced Raman Scattering (SERS) measurement, and 3D-printed cartridge to build enclosed environment for the improvement of detection, which cost only one dollar. The preconcentration ability of the cartridge was up to 18.13-fold fluorescence enhancement and compared to the non-preconcentration method, it achieved 9.93-fold improvement of SERS performance. The anticancer drug of epirubicin hydrochloride, cyclophosphamide and their mixtures were quantitatively detected in the bovine serum or artificial urine. The integrated detection procedure required only 1 h, including sample pretreatment and preconcentration, drying, SERS measurements, and quantification analysis. This 3D-printed paper cartridge constituted a portable detection platform that would be potentially a practical and point-of-care detection tool for drug preconcentration and quantification on the clinical diagnosis.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2018
·Vol. 6
·期 19
·3030-3039
·
IF 4.776
Chunyuan Song,Yanxia Dou,Lihui Yuwen,Youzhi Sun,Chen Dong,Fang Li,Yanjun Yang,Lianhui Wang
Accurate and effective drug delivery in tumor cells significantly improves the curative effect with high drug delivery efficiency, low toxicity and side effects and has become an urgent demand for anticancer therapy. In this paper, a novel traceable and targeted drug delivery nanosystem (i.e. AuNF-nanocarriers) with high drug encapsulation and pH-controlled release was prepared based on gold nanoflowers (AuNFs) for efficient intracellular SERS imaging-guided chemo-phototherapy. SERS-active flower-like gold nanoparticles with large surface area were synthesized first and then modified with Raman and RGD molecules in sequence to prepare bright, traceable and targeted SERS tags of A549 human lung cancer cells. Furthermore, thiolated-PAA (PAA-SH) was synthesized and utilized for the first time to modify the SERS tags with a layer of negative charges for efficient pH-dependent loading and release of the anticancer drug doxorubicin. Based on the A549 human lung cancer cell model, the availability of the proposed AuNF-nanocarriers for efficient intracellular SERS imaging-guided chemo-phototherapy was studied and the results indicate that the AuNF-based drug delivery system exhibited attractive characteristics such as good stability, efficiency and pH-controlled drug loading and release, traceable and targeted delivery, as well as SERS imaging and chemo-phototherapy functions, and shows great potential for powerful SERS-imaging and as a theranostic candidate for precision nanomedicine that could achieve sensitive and accurate tumor detection and therapy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2024
·
IF 14.7
Yunkun Li,Xiaoding Shen,Haitao Ding,Yuxin Zhang,Dayi Pan,Liping Su,Yahui Wu,Zaixiang Fang,Jie Zhou,Qiyong Gong,Kui Luo
Inefficient drug penetration hurdled by the stroma in the tumor tissue leads to a diminished therapeutic effect for drugs and a reduced infiltration level of immune cells. Herein, we constructed a PEGylated dendritic epirubicin (Epi) prodrug (Epi-P4D) to regulate the metabolism of cancer-associated fibroblasts (CAFs), thus enhancing Epi penetration into both multicellular tumor spheroids (MTSs) and tumor tissues in mouse colon cancer (CT26), mouse breast cancer (4T1) and human breast cancer (MDA-MB-231) models. Enhanced cytotoxicity against CT26 MTSs and remarkable antitumor efficacy of Epi-P4D were ascribed to reduced fibronectin, α -SMA, and collagen secretion. Besides, thinning of the tumor tissue stroma and efficient eradication of tumor cells promoted the immunogenic cell death effect for dendritic cell (DC) maturation and subsequent immune activation, including elevating the CD4 + T cell population, reducing CD4 + and CD8 + T cell hyperactivation and exhaustion, and amplifying the natural killer (NK) cell proportion and effectively activating them. As a result, this dendritic nanomedicine thinned the stroma of tumor tissues to enhance drug penetration and facilitate immune cell infiltration for elevated antitumor efficacy.
✓ 已验证
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）