Nanomedicine
·
2018
·
IF 5.005
Yuanyuan Xie,Xiaofan Zeng,Xian Wu,Jun Hu,Yanhong Zhu,Xiangliang Yang
Aim: To study the effects of combinational treatment of hyperbaric oxygen (HBO) and nanotemozolomide in glioma. Materials & methods: Temozolomide (TMZ)-loaded porous silicon nanoparticles (TMZ/PSi NPs) were prepared. In vitro and in vivo evaluations were performed. Results: The cell uptake of TMZ/PSi NPs could be tracked by autofluorescence of porous silicon. The concentration of oxygen in tumor was improved and the antitumor rate was increased to 84.2% in the TMZ/PSi NPs combined with HBO group. The viability of hypoxia-induced glioma C6 cells was decreased and cell cycle was arrested at G2/M phase in response to TMZ/PSi NPs treatment with HBO compared with continuous treatment with hypoxia. Conclusion: The combinational treatment of TMZ/PSi NPs and HBO could be a promising therapeutic strategy for glioma.
研究领域:
肿瘤学
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药理学
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神经科学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2021
·Vol. 11
·期 8
·4444-4453
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IF 3.361
Ruotong Liu,Chanling Yuan,Yin Feng,Jiayi Qian,Xiaoting Huang,Qiutong Chen,Shuyuan Zhou,Yin Ding,Bingbing Zhai,Wenjie Mei,Liangzhong Yao
Ru(II) complexes have attracted increasing attention as promising antitumor agents for their relatively low toxicity, high affinity to DNA molecules, and correlation with multiple targets. Meanwhile, quinolones are synthetic antibacterial agents widely used in the clinical practice. In this paper, two novel Ru(II) complexes coordinated by levofloxacin (LOFLX), [Ru(bpy)2(LOFLX)]·2ClO4 (1), and [Ru(dmbpy)2(LOFLX)]·2ClO4 (2) (bpy = 2,2′-bipyridine, dmbpy = 4,4′-dimethyl-2,2′-bipyridine) were synthesized with high efficiency under microwave irradiation and characterized by ESI-MS, 1H NMR, and 13C NMR. The binding behavior of these complexes with double-strand calf thymus DNA(CT-DNA) was investigated using spectroscopy, molecular docking, and density functional theory calculations. Results showed that 2 exhibited higher binding affinity than 1 and LOFLX. Further studies showed that 2 could induce the G2/M phase arrest of A549 cells via DNA damage. In summary, these results indicated that 2 could be developed as a potential anticancer agent in treatment of lung cancer through the induction of cell cycle arrest at G2/M phase by triggering DNA damage.
研究领域:
药理学
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肿瘤学
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生物化学
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DOI
PubMed
高影响因子
RSC Advances
·
2017
·Vol. 7
·期 43
·26625-26632
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IF 3.108
Jieqiong Cao,Qiong Wu,Wenjie Zheng,Li Li,Wenjie Mei
A series of polypyridyl ruthenium(II) complexes coordinated by phenanthroimidazole derivatives [Ru(phen)2(R)](ClO4)2 (where 1 R = IP, 2 R = PIP, 3 R = p-HPIP, 4 R = p-OCH3PIP) was synthesized with an average yield of >85% under microwave irradiation at 140 °C for 30 min. The inhibitory effect of these complexes against various tumour cells were evaluated by MTT assay, and the results showed that these polypyridyl ruthenium(II) complexes exhibited acceptable inhibition against different tumour cells, especially 4, with an IC50 of 18.4 μM for Hela cells. The results showed that 4 inhibited the growth of cervical cancer Hela cells by inducing G2/M phase arrest, which was followed by slight apoptosis. Further studies showed that 4 displayed better inhibition against the invasion and metastasis of Hela cells than NAMI-A. Studies on the in vivo distribution and metabolism indicated that 4 was rapidly distributed in the entire body, absorbed by the tumour tissue and had only a small accumulation of toxicity in the body. These results demonstrated that this type of ruthenium(II) complex can block the growth of Hela cells and inhibit their migration and invasion through G2/M phase arrest, which suggests the complex could act as a potential tumour-targeting inhibitor in future clinical applications.
研究领域:
药理学
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肿瘤学
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生物化学
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产品关联
DOI
PubMed
高影响因子
Chemical Biology & Drug Design
·
2023
·Vol. 102
·期 1
·101-114
·
IF 3
Meiya Mao,Xiaojiao Zheng,Yuehua Sheng,Jinghan Chai,Huiqing Ding
Evodiamine (EVO) has been demonstrated to promote apoptosis of ovarian cancer cells, and upregulate miR-152-3p level in colorectal cancer. Here, we explore part of the network mechanism of EVO and miR-152-3p in ovarian cancer. The bioinformatics website, dual luciferase reporter assay, and quantitative real-time polymerase chain reaction were applied to analyze the network among EVO, lncRNA, miR-152-3p, and mRNA. The effect and mechanism of EVO on ovarian cancer cells were determined using cell counting kit-8, flow cytometry, TUNEL, Western blot, and rescue experiments. As a result, EVO dose-dependently attenuated cell viability, induced G2/M phase arrest and apoptosis, promoted miR-152-3p level (4.5- or 2-fold changes), and inhibited expressions of NEAT1 (0.225- or 0.367-fold changes), CDK8 (0.625- or 0.571-fold changes), and CDK19 (0.25- or 0.147-fold changes) in OVCAR-3 and SKOV-3 cells. In addition, EVO decreased Bcl-2 expression, but increased the expressions of Bax and c-caspase-3. NEAT1 targeted miR-152-3p which bound to CDK19. The impacts of EVO on cell viability, cycle, apoptosis, and apoptosis-related proteins were partially reversed by miR-152-3p inhibitor, NEAT1 overexpression, or CDK19 overexpression. Furthermore, miR-152-3p mimic offset the effects of NEAT1 or CDK19 overexpression. The role of NEAT1 overexpression in the biological phenotype of ovarian cancer cells was counteracted by shCDK19. In conclusion, EVO attenuates ovarian cancer cell progression via the NEAT1-miR-152-3p-CDK19 axis.
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2025
·
IF 4.7
Hafiz Muhammad Bilal Akram,Yulin Liu,Jianshu Dong,Xueke Zhao,Lidong Wang,Wen Zhao,Hongmin Liu,Liying Ma,Cong Han
Esophageal cancer has been regarded as a serious malignancy due to its poor prognosis and high mortality rate. Serine hydroxymethyltransferase 2 (SHMT2) is emerging as an attractive target for esophageal cancer therapy. Compound W478 was identified as a potent SHMT2 inhibitor with an IC 50 value of 1.21 μM, especially whose chemical structure is distinct from the reported SHMT2 inhibitors. Both cellular thermal shift assay and isothermal titration calorimetry experiments showed that compound W478 tightly bound to SHMT2 (K D = 10.6 ± 1.2 μM). The molecular docking analysis revealed its binding at the folate binding site of SHMT2. Moreover, compound W478 exhibited a significant antiproliferative effect on human esophageal cancer cell lines, KYSE-450 and KYSE-70 cells (IC 50 = 1.62 μM, 1.18 μM, respectively). The wound healing and transwell assays showed that compound W478 could inhibit the migratory and invasive potential of KYSE-450 and KYSE-70 cells in a dose-dependent manner. Further studies demonstrated that compound W478 could induce cell arrest at the G2/M phase and promote cell apoptosis and ROS production in KYSE-450 and KYSE-70 cells. These findings indicated that compound W478 could serve as a promising lead compound for the development of SHMT2 inhibitor to address esophageal carcinoma.
研究领域:
肿瘤学
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分子生物学
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药物化学
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转化医学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR PHYSIOLOGY
·
2019
·Vol. 235
·期 3
·2911-2924
·
IF 4.522
Qiuyue Ding,Wenda Zhang,Cheng Cheng,Fengbo Mo,Lei Chen,Guangfu Peng,Xianyi Cai,Jinglong Wang,Shuhua Yang,Xianzhe Liu
Pyroptosis is a form of programmed cell death (PCD) that plays a vital role in immunity and diseases. Although it was recently reported that chemotherapy drugs can induce pyroptosis through caspase-3-dependent cleavage of gasdermin E (GSDME), the role of pyroptosis in osteosarcoma (OS) with dioscin is less understood. In this study, we explored the effects of dioscin on OS in vitro and in vivo and further elucidated the underlying molecular mechanisms and found that dioscin-triggered pyroptosis in GSDME-dependent cell death and that GSDME-N was generated by caspase-3. Furthermore, dioscin inhibited cancer cell growth by inducing G2/M arrest and apoptosis through the JNK/p38 pathway. In vivo, dioscin significantly inhibited OS proliferation. Taken together, our results demonstrate that dioscin can induce apoptosis through the JNK/p38 pathway and GSDME-dependent pyroptosis in OS, identifying it as a potential therapeutic drug for treatment of this disease. HIGHLIGHTS Dioscin triggers pyroptosis in osteosarcoma. Gasdermin E is a mediator of dioscin-induced osteosarcoma (OS) cell death. Dioscin induces apoptosis and G2/M arrest. Dioscin inhibits OS proliferation in vitro and in vivo.
研究领域:
肿瘤学
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细胞生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2025
·
IF 4.7
Hongyan Lin,Shuaijun Cui,Xinye Xu,Qingqing Chen,Jiazi Ge,Dongxuan Ai,Jie Zhu,Yuheng Tao,Liqun Wang,Lingyu Ruan,Wenhao Ge
18β-Glycyrrhetinic acid (18β-GA) is the main active component of licorice and one of the most promising lead compounds in traditional Chinese herbal medicine. Previous studies have shown that 18β-GA can act as a PPARγ agonist to exert antitumor activity. However, the number of reported 18β-GA derivatives as PPARγ agonists is limited and they have significant toxic side effects, which greatly restricts their application and development. To obtain highly effective and low-toxic PPARγ agonists, through structure-activity relationship (SAR) analysis, we constructed a molecular library of 18β-GA derivatives containing 13,440 compounds and screened out 14 novel 18β-GA ester derivatives. The selected compounds were evaluated for their antitumor activity in vitro. The results showed that most of the compounds exhibited strong anti-proliferative activity against five human cancer cell lines, especially the human colon cancer cell line HT-29, without significant toxicity to normal cell lines. Among them, C1 had the strongest anti-proliferative activity against HT-29, with an IC 50 value of 12.25 μM, which was 12 times higher than that of its parent nucleus 18β-GA. C1 can block the cell cycle of HT-29 cells in G2/M phase, significantly inhibit their migration and induce their apoptosis. Molecular docking and dynamics simulation results suggested that C1 could stably bind to the active pocket of PPARγ. Further PPARγ activity analysis and drug-likeness prediction results indicated that C1 could act as a PPARγ agonist to exert antitumor effects and had certain drug-likeness, which is worthy of further study.
研究领域:
药理学
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药物化学
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肿瘤学
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DOI
PubMed
高影响因子
ONCOLOGY REPORTS
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2020
·Vol. 44
·期 3
·1116-1126
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IF 3.417
Kang An,Yuehan Zhang,Yingjiao Liu,Shengxi Yan,Zhaowei Hou,Meng Cao,Guangkuo Liu,Congcong Dong,Juncha Gao,Gaifang Liu
Current treatments for esophageal squamous cell carcinoma (ESCC) have limited efficacy. Therefore, the development of novel therapeutic targets to effectively manage the disease and boost survival rates is imperative Neferine, a natural product extracted from Nelumbo nucifera (lotus) leaves, has been revealed to inhibit the growth of hepatocarcinoma, breast cancer and lung cancer cells. However, its effect on ESCC is unknown. In the present study, it was revealed that neferine exerted anti‑proliferative effects in ESCC. It was also revealed that it triggered arrest of the G2/M phase and enhanced apoptosis of ESCC cell lines. Moreover, its ability to trigger accumulation of reactive oxygen species (ROS) and activate the c‑Jun N‑terminal kinase (JNK) pathway was demonstrated. Further study revealed how N‑acetyl cysteine (NAC), a ROS inhibitor, attenuated these effects, demonstrating that ROS and JNK inhibitors mediated a marked reversal of neferine‑triggered cell cycle arrest and apoptosis in ESCC cells. Finally, it was revealed that neferine was involved in the inhibition of Nrf2, an antioxidant factor. Collectively, these findings demonstrated the antitumor effect of neferine in ESCC, through the ROS‑mediated JNK pathway and inhibition of Nrf2, indicating its potential as a target for development of novel and effective therapeutic agents against ESCC.
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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天然产物
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2013
·
IF 2.596
Xiaofen Xu,Yanggong Li,Yuanyuan Shen,Shengrong Guo
Norcantharidin-conjugated chitosan conjugates (NCTD-CSs) with different degrees of substitution ( DS , 60.2% and 97.9%) were synthesized and characterized by 1 H NMR, FT-IR, and XRD. In comparison with CS, the NCTD-CSs had lower crystallinity and better water solubility. Less than 6% NCTD was released from the NCTD-CSs through the hydrolysis of ester bonds in phosphate-buffered solution (PBS, pH 5.0 and 7.4) within 16 days, showing sustained drug release characteristic. The result of cytoxicity study showed that the NCTD-CSs were cytotoxic to MGC80-3 cells and their cytotoxicity was lower than that of NCTD. Fluorescence microscope and flow cytometry analysis demonstrated that the amount of the NCTD-CSs uptaken by MGC80-3 cells increased as incubation time. Confocal microscopy study showed that the NCTD-CSs were internalized into cells by endocytosis and mainly localized in lysosomes within 24 h. It was found that the NCTD-CSs arrested MGC80-3 cell cycle at G2/M phase and induced cell death via cell apoptosis similarly to NCTD. These results indicated that the NCTD-CSs might be an efficient NCTD delivery system for cancer therapy.
研究领域:
药学
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肿瘤学
·
材料科学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2019
·
IF 4.18
Jun-Shan Liu,Chu-Ying Huo,Hui-Hui Cao,Chun-Lin Fan,Jian-Yang Hu,Li-Juan Deng,Zi-Bin Lu,Hua-Yi Yang,Lin-Zhong Yu,Zhi-Xian Mo,Zhi-Ling Yu
Background Hepatocellular carcinoma (HCC) ranks third among the most common causes of cancer-related deaths worldwide. The chemotherapy for HCC is still insufficient, so far. In searching for effective anti-HCC agents from traditional Chinese medicine , we discovered that aloperine (ALO), a quinolizidine alkaloid from Sophora alopecuroides L., exerts anti-HCC activities. However, the effects of ALO on HCC have been rarely studied, and its underlying mechanisms remain unknown. Purpose This study aims to evaluate the anti-HCC activities of ALO and explore its underlying mechanisms. Methods MTT assay and colony formation assay were used to investigate the anti-proliferative effects of ALO on human HCC Hep3B and Huh7 cells. Hoechst 33258 staining was used to observe the morphological changes of cells after ALO treatment . Flow cytometry was used to analyze apoptosis induction, the collapse of the mitochondrial membrane potential and cell cycle distribution. Western blotting was used to examine the expression levels of proteins associated with apoptosis and cell cycle arrest , and key proteins in the PI3K/Akt signaling pathway . Small interfering RNA (siRNA) transfection was used to investigate the role of Akt in ALO-induced apoptosis and cell cycle arrest. Zebrafish tumor model was used to evaluate the anti-HCC effects of ALO in vivo. Results ALO inhibited the proliferation of Hep3B and Huh7 cells. ALO induced apoptosis in HCC cells, which was accompanied by the loss of mitochondrial potential, the release of cytochrome c into cytosol, as well as the increased cleavages of caspase-9, caspase-3 and PARP . Moreover, ALO induced G2/M cell cycle arrest by downregulating the expression levels of cdc25C, cdc2 and cyclin B1 . In addition, ALO inhibited activation of the PI3K/Akt signaling pathway by decreasing the expression levels of p110α , p85, Akt and p-Akt (Ser473) . Further study showed that inhibition of Akt by siRNA augmented ALO-mediated apoptosis and G2/M cell cycle arrest in HCC cells. Critically, ALO inhibited the growth of Huh7 cells in vivo. Conclusion We first demonstrated that ALO induced apoptosis and G2/M cell cycle arrest in HCC cells through inhibition of the PI3K/Akt signaling pathway. This study provides a rationale for ALO as a potential chemotherapeutic agent for HCC.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Xiaoliang Li,Mingyan Zhou,Zhe Zhu,Zhe Wang,Xuguang Zhang,Lu Lu,Zhenrui Xie,Bingshu Wang,Yipeng Pan,Junqing Zhang,Jian Xu
Ethnopharmacological relevance Alpinia officinarum Hance ( A . officinarum ), a perennial herb known for its medicinal properties, has been used to treat various ailments, such as stomach pain, abdominal pain, emesis, and digestive system cancers. A . officinarum is extensively cultivated in the Qiongzhong and Baisha regions of Hainan, and it holds substantial therapeutic value for the local Li people of Hainan. Kaempferol, a flavonoid derived from A . officinarum , has demonstrated anticancer properties in various experimental and biological studies. Nevertheless, the precise mechanisms through which it exerts its anti-hepatocellular carcinoma (HCC) effects remain to be comprehensively delineated. Aim of the study This investigation aims to elucidate the anti-HCC effects of kaempferol derived from A . officinarum and to delve into its underlying mechanistic pathways. Materials and Methods Using ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry (UPLC-MS/MS) to identify active compounds in A. officinarum . HCCLM3 and Huh7 cells were used to study the anti-HCC effect of kaempferol from A . officinarum . The cytotoxicity and proliferation of kaempferol and A . officinarum were measured using CCK-8 and EDU staining. Wound-healing assays and three-dimensional tumor spheroid models were further used to evaluate migration and the anti-HCC activity of kaempferol. The cell cycle and apoptosis were evaluated by flow cytometry. Western blot and qRT-PCR were used to detect the expression of proteins and genes associated with the cell cycle checkpoints. Finally, bioinformatics was used to analyze the relationship between the differential expression of core targets in the ATM/CHEK2/KNL1 pathway and a poor prognosis in clinical HCC samples. Results UPLC-MS/MS was employed to detect five active compounds in A . officinarum , such as kaempferol. The CCK-8 and EDU assays showed that kaempferol and A . officinarum significantly inhibited the proliferation of HCC cells. A wound-healing assay revealed that kaempferol remarkably inhibited the migration of HCC cells. Kaempferol significantly suppressed the growth of tumor spheroids. In addition, kaempferol markedly induced G2/M arrest and promoted apoptosis of HCC cells. Mechanically, kaempferol significantly reduced the protein and mRNA expression levels of ATM, CHEK2, CDC25C, CDK1, CCNB1, MPS1, KNL1, and Bub1. Additionally, the combination of kaempferol and the ATM inhibitor KU55933 had a more significant anti-HCC effect. The results of bioinformatics showed that ATM, CHEK2, CDC25C, CDK1, and KNL1 were highly expressed in patients with HCC and cancer tissues, indicating that these genes have certain value in the clinical diagnosis of HCC. Conclusions Collectively, our results revealed that kaempferol from A . officinarum inhibits the cell cycle by regulating the ATM/CHEK2/KNL1 pathway in HCC cells. In summary, our research presents an innovative supplementary strategy for HCC treatment.
研究领域:
药理学
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肿瘤学
·
细胞生物学
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分子生物学
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生物信息学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Chemistry
·
2025
·
IF 4.2
Zhihong Hu,Xixi Hou,Yongjing Ren,Ziyuan Wu,Dong Yan,Hong Chen,Lan Wang
Cervical cancer ranks as the fourth most common cancer among women. However, the current treatments have significant side effects and limited therapeutic effects on advanced diseases, so it is necessary to discover better treatments for cervical cancer. The current study investigated the potential anticancer effects of a series of gefitinib-1,2,3-triazole derivative on Hela cells. Among the investigated, the target compound c13 showed good anticancer activity against Hela cells (IC50 = 5.66 ± 0.35 μM) compared with gefitinib (IC50 = 14.18 ± 3.19 μM). Moreover, compound c13 significantly inhibited the colony formation ability of Hela cells in a dose-dependent manner, accompanied by morphological changes in HeLa cells. Further investigations demonstrated that compound c13 triggered cell apoptosis and arrested the cell cycle at the G2/M phase in Hela cells. In addition, western blot analysis revealed that compound c13 upregulated the Bax/Bcl-2 ratio, and increased the levels of active caspase 3 and PARP1 cleavage, which suggested the involvement of the mitochondrial pathway in compound c13-induced apoptosis. In brief, these results indicated that compound c13 is a promising compound for the treatment of cervical cancer.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
✓ 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）