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
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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
Acta Biomaterialia
·
2021
·
IF 8.947
Suleixin Yang,Ka Hong Wong,Peng Hua,Chengwei He,Hua Yu,Dan Shao,Zhi Shi,Meiwan Chen
Ferroptosis is a newly discovered non-apoptotic cell death form but its therapeutic efficacy triggered by traditional iron-based nanomaterials or classic drug inducers has been far from satisfactory due to the high glutathione (GSH) level in cancer cells and insufficient lipid peroxide production. Here we reported a ferroptosis/apoptosis combinational therapy by depleting GSH and downregulating GPX4 to disrupt redox homeostasis and amplify ferroptosis-related oxidation effect. In this study, we developed reactive oxygen species (ROS)-responsive serum-resistant nanoparticles with thioketal-crosslinked fluorinated polyethyleneimine 1.8K ( TK PF) as the core, which were wrapped with hyaluronic acid (HA) as the shell ( TK PFH NP) to co-deliver shGPX4 and shMTHFD2 plasmids for cancer treatment. The highly efficient and tumor-selective gene carrier TK PFH NPs revealed outstanding transfection efficiency (∼100 %) and sustained the efficiency (∼50 %) even in media containing 90 % FBS. Mediated by HA, TK PFH NPs actively targeted CD44 receptors, thus enabling efficient uptake by tumor cells and experiencing surface charge conversion to induce subsequent lysosomal escape. Then the TK PF NPs were effectively disintegrated by the abundant ROS in cancer cells, which facilitated the release of plasmids and avoided the cytotoxicity of cationic polymers. shGPX4 plasmid induced ferroptosis by producing ROS and lipid peroxides via downregulating GPX4, while shMTHFD2 triggered apoptosis by modulating NADPH/NADP and depleting GSH of the cancer cells. Moreover, GSH consumption caused by shMTHFD2 indirectly suppressed GPX4 and further augmented ferroptosis, showing synergistic anticancer effect against B16-F10 cells. Taken together, the rationally designed dual-gene loaded TK PFH NPs provided a safe and high-performance platform for enhanced ferroptosis-apoptosis combined anticancer efficacy based on gene therapy. Statement of significance The therapeutic efficacy of ferroptosis has been far from satisfactory due to high GSH level and insufficient lipid peroxide production in cancer cells. Herein, we reported a ferroptosis/apoptosis combinational therapy by depleting GSH and downregulating GPX4 to disrupt redox homeostasis and amplify ferroptosis-related oxidation effect. ROS-responsive serum-resistant nanoparticles were fabricated with thioketal-crosslinked fluorinated PEI 1.8K ( TK PF) as the core and hyaluronic acid (HA) as the shell ( TK PFH NP) to co-deliver shGPX4 and shMTHFD2 plasmids. The shGPX4 plasmid induced ferroptosis by producing ROS and lipid peroxides via downregulating GPX4, while shMTHFD2 triggered apoptosis by modulating NADPH/NADP and depleting GSH. The rationally designed dual-gene loaded TK PFH NPs provided a safe and high-performance platform aimed for enhanced ferroptosis-apoptosis combined anticancer efficacy.
研究领域:
癌症治疗
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纳米技术
·
基因递送
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生物医学工程
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2022
·
IF 5.395
Wei Guo,Wenchang Liu,Pengqi Wan,Hao Wang,Chunsheng Xiao,Li Chen,Xuesi Chen
Cancer has become the leading cause of human death worldwide, and there is an urgent need to design and develop new oncology drugs. In this study, we report series of cationic amphiphilic dendrons with different hydrophobic alkyl chains (Cn) and different generations (Gx) and demonstrate their use for anticancer applications. The results revealed that lower-generation dendrons (G1) with a longer hydrophobic alkyl chain (C12 and C18) have stronger antitumor activity. Among these dendrons, a lead candidate C12–G1 was identified that demonstrated excellent broad-spectrum antitumor activity in 7 cancer cell lines including highly metastatic tumor cells, while simultaneously, hemolysis was negligible. Mechanistic studies showed that C12–G1 could lead to cytoplasmic leakage and induce cancer cell necrosis through membrane disruption. In addition, C12–G1 showed potent inhibition of tumor growth in a B16–F10 melanoma model. In conclusion, these findings demonstrate that the cationic amphiphilic dendron might be a promising agent for anticancer application.
研究领域:
药学
·
肿瘤学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Xing Zhao,Haifei Guo,Hriday Bera,Huiyang Jiang,Yang Chen,Xiong Guo,Xidong Tian,Dongmei Cun,Mingshi Yang
Paclitaxel (PTX) remains a cornerstone in the treatment of locally advanced and metastatic lung cancer. To improve its therapeutic indices against lung cancer, novel redox-sensitive pullulan/PTX-based prodrug NPs (PULL–SS–PTX NPs) were accomplished, which were further surface-decorated with transferrin (TF), a cancer cell-targeting ligand, to afford TF–PULL–SS–PTX NPs. These prodrug NPs (drug content, >37% and average size, 134–163 nm) rapidly dismantled their self-assembled architecture upon exposure to simulated reducing conditions, causing a triggered drug release as compared to the control scaffold (PULL–CC–PTX NPs). These scaffolds also evidenced outstanding colloidal stability, cellular uptake efficiency, and discriminating cytotoxicity between the cancer and healthy cells. Intravenously delivered redox-sensitive NPs exhibited improved tumor-suppressing properties as compared to the control nanovesicles (PULL–CC–PTX NPs) in a B16–F10 melanoma lung metastasis mice model. The targeting efficiency and associated augmented anticancer potentials of TF–PULL–SS–PTX NPs relative to TF-free redox-responsive NPs and Taxol intravenous injection were also established on the transferrin receptor (TFR) overexpressed Lewis lung carcinoma (LLC–luc) cell-bearing mice model. Moreover, the TF-functionalized scaffold displayed a reduced systemic toxicity compared to that of Taxol intravenous injection. Overall, the proposed TF-decorated prodrug NPs could be a promising nanomedicine for intracellular PTX delivery against metastatic lung cancer.
研究领域:
药学
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纳米技术
·
肿瘤学
·
药物递送系统
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2024
·
IF 7.6
Yanyan Meng,Shaoqing Chen,Pengyin Li,Cheli Wang,Xinye Ni
Melanoma is a highly invasive and lethal skin cancer with a strong tendency to metastasize and has a poor prognosis. Radiotherapy is one of the important treatments for melanoma. In this study, monoglyceride solid lipid nanoparticles (MG SLNs) were wrapped with the B16-F10 cell membrane (B16 CM) for the fabrication of B16@MG. B16@MG had low toxicity and specifically targeted B16-F10 cells. B16-F10 tumor–bearing mouse model showed that indocyanine green (ICG) -loaded B16@MG achieved long-term accumulation in the tumor and facilitated the localization of the tumor boundary. MG SLNs were encapsulated with methyl 5-aminolevulinate (MLA) and desferrioxamine (DFO), and B16 CM was wrapped around their surfaces to obtain B16@MG–MLA–DFO.MLA was metabolized to protoporphyrin IX (PpIX) in the cells and DFO reduced the content of iron ion in the cells, blocked the biotransformation of PpIX, and promoted the accumulation of PpIX in the cells. The results of mitochondrial reactive oxygen species (ROS) and membrane potential detection showed that PpIX enhanced the generation of ROS, caused DNA and mitochondrial damage, and led to the apoptosis of tumor cells under radiotherapy. In B16-F10 tumor–bearing mice, B16@MG–MLA–DFO can improve the efficacy of radiotherapy and allow the integration of diagnosis and treatment.
研究领域:
肿瘤学
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纳米技术
·
药理学
·
放射生物学
✓ 已验证
产品关联
DOI
高影响因子
MOLECULES
·
2024
·Vol. 29
·期 20
·4962
·
IF 4.2
Yu-Dan Wang,Lu-Sheng Han,Gen-Yue Li,Kai-Li Yang,Yan-Long Shen,Hao Zhang,Jian-Feng Hou,En-Peng Wang
This study was conducted to investigate the differences in chemical composition between red (RGBs) and yellow ginseng berries (YGBs) and their whitening and anti-aging skincare effects. The differences in the chemical composition between RGB and YGB were analyzed by ultra-high-performance liquid chromatography tandem quadrupole electrostatic field orbit trap mass spectrometry (UHPLC-Q-Exactive-MS/MS) combined with multivariate statistics. An aging model was established using UVB radiation induction, and the whitening and anti-aging effects of the two ginseng berries were verified in vitro and in vivo using cell biology (HaCaT and B16-F10 cells) and zebrafish model organisms. A total of 31 differential compounds, including saponins, flavonoids, phenolic acids, and other chemical constituents, were identified between the two groups. Superoxide dismutase (SOD) activity was more significantly increased (p< 0.05) and malondialdehyde (MDA) content was more significantly decreased (p< 0.01) in RGB more than YGB induced by UVB ultraviolet radiation. In terms of whitening effects, YGB was more effective in inhibiting the melanin content of B16-F10 cells (p< 0.01). The results of zebrafish experiments were consistent with those of in vitro experiments and cell biology experiments. The DCFH fluorescence staining results revealed that both ginseng berries were able to significantly reduce the level of reactive oxygen species (ROS) in zebrafish (p< 0.01). Comparison of chemical composition and skin care activities based on RGB and YGB can provide a theoretical basis for the deep development and utilization of ginseng berry resources.
研究领域:
药用植物学
·
化妆品科学
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分析化学
·
细胞生物学
·
动物模型
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2023
·Vol. 415
·期 12
·2249-2260
·
IF 4.3
Guo Fei-Fei,Li Tong,Mu Xi-Ping,Zhang Xue,Xu Zhi-Hao,Sun Ping,Yu Ri-Lei,Xia Ya-Mu,Gao Wei-Wei
In this work, we design and synthesize 2,2′-(7,9-dimethyl-2,4,6,8-tetraoxo-6,7,8,9-tetrahydropyrimido[5,4-g]pteridine-1,3(2H,4H)-diyl)bis( N,N -bis(2-chloroethyl)acetamide) (PT-MCA) as a novel DNA intercalator and potential antitumor agent. Electrochemical analysis reveals the redox process of PT-MCA on the electrode surface. The bioelectrochemical sensors are obtained by modifying the surface of GCE with calf thymus DNA (ctDNA), poly (dG), poly (dA), and G-quadruplex, respectively. The DNA oxidative damage induced by PT-MCA is investigated by comparing the peak intensity change of dGuo and dAdo and monitoring the peaks of the oxidation products of guanine and/or adenine (8-oxoGua and/or 2,8-oxoAde). UV–vis absorption and fluorescence spectra and gel electrophoresis are further employed to understand the intercalation of PT-MCA into DNA base pairs. Moreover, PT-MCA is proved to exhibit stronger anti-proliferation activity than mitoxantrone against both 4T1 and B16-F10 cancer cells. At last, the oxidative damage of PT-MCA toward ctDNA is not interfered by the coexistence of ions and also can be detected in real serums. Graphical abstract
研究领域:
药物化学
·
生物化学
·
癌症研究
·
电化学
·
分子生物学
✓ 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）