FITOTERAPIA
·
2016
·
IF 2.408
Wen-Jia Kang,Da-Hong Li,Tong Han,Lin Sun,Yan-Bin Fu,Chun-Mei Sai,Zhan-Lin Li,Hui-Ming Hua
Investigation of the roots of Flemingia philippinensis resulted in the isolation of two new chalcones , flemiphilippinones B ( 1 ) and C ( 2 ), and one new pterocarpoid, demethylwedelolactone-11-methyl ether ( 3 ), together with 12 known compounds ( 4 - 15 ). The antiproliferative activity against PC-3 cells was evaluated and most compounds showed cytotoxicity, among which, compound 2 exhibited GI 50 value of 14.12 μM. The antiproliferative activity of 2 against Bel-7402 and CaEs-17 cells was also measured, with GI 50 values of 1.91 and 2.58 μM, respectively. Intensive mechanism study showed that 2 caused cell-cycle arrest at S/G 2 phase and induced apoptosis in Bel-7402 cells through mitochondria-related pathway.
研究领域:
药用植物化学
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肿瘤生物学
·
细胞信号通路研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF INORGANIC BIOCHEMISTRY
·
2013
·
IF 3.197
Zhen Zhang,Caifeng Bi,Daniela Buac,Yuhua Fan,Xia Zhang,Jian Zuo,Pengfei Zhang,Nan Zhang,Lili Dong,Q. Ping Dou
Although cadmium (Cd) is a widespread environmental contaminant and human carcinogen, our studies indicate an organic Cd complex to be a potent inhibitor of proteasomal chymotrypsin-like (CT-like) activity, further capable of inducing apoptosis in a cancer cell-specific manner. It has been reported that the ligands indole-3-butyric acid (L1) and indole-3-propionic acid (L2) have cancer-fighting effects when tested in a rat carcinoma model. In addition, 3, 5-diaminobenzoic acid o-vanillin Schiff bases (L3) have high antimicrobial activity and a large number of Schiff base complexes have been reported to have proteasome-inhibitory activity. We therefore hypothesized that synthetic forms of Cd in combination with L1, L2 and L3 may have proteasome-inhibitory and apoptosis-inducing activities, which would be cancer cell-specific. To test this hypothesis, we have synthesized three novel Cd-containing complexes: [Cd 2 (C 12 H 12 O 2 N) 4 (H 2 O) 2 ]·2H 2 O (Cd1), [Cd 2 (C 11 H 10 O 2 N) 4 (H 2 O) 2 ]·2H 2 O (Cd2) and [Cd(C 7 H 4 N 2 O 2 )(C 8 H 6 O 2 ) 2 ]·2H 2 O (Cd3), by using these three ligands. We sought out to characterize and assess the proteasome-inhibitory and anti-proliferative properties of these three Cd complexes in human breast cancer cells. Cd1, Cd2 and Cd3 were found to effectively inhibit the chymotrypsin-like activity of purified 20S proteasome with IC 50 values of 2.6, 3.0 and 3.3 μΜ, respectively. Moreover, inhibition of cancer cell proliferation also correlated with this effect. As a result of proteasomal shutdown, the accumulation of ubiquitinated proteins and the proteasome target IκB-α protein as well as induction of apoptosis were observed. To account for the cancer specificity of this effect, immortalized, non-tumorigenic breast MCF10A cells were used under the same experimental conditions. Our results indicate that MCF10A cells are much less sensitive to the Cd1, Cd2 and Cd3 complexes when compared to MDA MB 231 breast cancer cells. Therefore, our study suggests that these Cd organic complexes are capable of inhibiting tumor cellular proteasome activity and consequently induce cancer cell-specific apoptotic death.
研究领域:
肿瘤学
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药理学
·
分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Kai Sun,Lingling Ma,Jiantong Hou,Yinglan Li,Haojing Jiang,Wenhui Liu,Ruyu Cao,Linsu Zhang,Yuanqiang Guo
Selenium nanoparticles (SeNPs) have attracted considerable attention in the field of cancer therapy due to their remarkable biological activities and advantageous nanoscale properties. However, their inherent instability presents a considerable challenge for broader applications. To address this issue, the heteropolysaccharide extracted from golden berries (the fruits of Physalis peruviana ), designated as DLG, was utilized to synthesize heteropolysaccharide-conjugated selenium nanoparticles, named DLG-SeNP3. Subsequent characterization showed that the nanoparticles DLG-SeNP3 were spherical, with an average particle size of 77 nm, a zeta potential of −14.4 mV, and excellent stability under physiological pH conditions. Further biological investigations showed that DLG-SeNP3 effectively inhibited tumor cell proliferation, exhibiting an IC 50 value of 41.60 μg/mL against A549 cells, and induced apoptosis, with a proportion of 31.30 % at 100 μg/mL. Moreover, in vivo experiments demonstrated that DLG-SeNP3 not only inhibited angiogenesis, resulting in a 26.51 % decrease at 2 μg/mL, but also suppressed tumor growth and invasion, with reductions of 76.90 % and 66.67 % in the intensity and foci of red fluorescence, respectively, at 2 μg/mL. In conclusion, DLG-SeNP3, stabilized with polysaccharides derived from golden berries, shows promising potential for application in cancer treatment.
研究领域:
生物医学工程
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肿瘤学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2013
·Vol. 1
·期 9
·1326-1332
·
IF 0
Wei Cui,Yue Cui,Jie Zhao,Junbai Li
Layer-by-layer assembled TRAIL/ALG shells have been successfully coated on the surface of highly loaded doxorubicin (DOX) calcium carbonate (CaCO3) nanoparticles as drug carriers. The assembled core/shell structure was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and confocal laser scanning microscopy (CLSM). They show that the assembled TRAIL/ALG coated DOX@CaCO3 nanocomposites can be internalized by cancer cells. The outer layer of the system is TRAIL which can be specifically recognized by tumors and leads to the apoptosis of tumors. The release of DOX can directly kill the cancer cells. This demonstrates that the core/shell nanocomposites of TRAIL/ALG-CaCO3 loaded with DOX have good potential applications in the treatment of cancer.
研究领域:
生物医学工程
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纳米医学
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肿瘤学
✓ 已验证
DOI
PubMed
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2015
·
IF 3.368
Wei Cui,Anhe Wang,Jie Zhao,Xiaoke Yang,Peng Cai,Junbai Li
Crosslinked albumin nanoparticles which loaded with doxorubicin (DOX) were fabricated with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and biocompatible polysaccharide, alginate (ALG), using layer-by-layer technique. Albumin nanoparticles exhibited narrow size distribution and fluorescent property. The assembled core/shell structure of the nanoparticles can be internalized more easily with the cancer cells, which attributes to TRAIL binding with death receptors. TRAIL still hold bioactive properties after assembled onto the particles. In addition, after loaded into the albumin core nanoparticles, DOX (as the chemotherapeutics) display a synergistic cytotoxic effect on cytotoxicity in combination with TRAIL in vitro . The core/shell nanostructured nanoparticles realized in this study would be used as a promising candidate for novel drug carriers.
研究领域:
药剂学
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肿瘤学
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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-26
·
IF 15.7
Li Kai,Yu Xuan,Xu Yanteng,Wang Haixia,Liu Zheng,Wu Chong,Luo Xing,Xu Jiancheng,Fang Youqiang,Ju Enguo,Lv Shixian,Chan Hon Fai,Lao Yeh-Hsing,He Weiling,Tao Yu,Li Mingqiang
Non-nucleotide stimulators of interferon gene (STING) agonists hold promise as immunotherapeutic agents for postsurgical adjuvant treatment of tumors. However, their limited effect duration hampers therapeutic effectiveness, necessitating prolonged administration of multiple doses that heightens infection risk and impacts patient compliance. Here, we develop an implantable dual-drug depot in a sandwich-like configuration, with a non-nucleotide STING agonist (MSA-2) in the outer layers of 3D-printed scaffolds and an immunogenic apoptosis inducer (doxorubicin, DOX) in the inner layer of electrospun fibers. We discover that MSA-2 can elicit endoplasmic reticulum stress-mediated and general immunogenic apoptosis of cancer cells. The stimulations with tumor-associated antigens and damage-associated molecular patterns from cancer cells, along with proinflammatory factors secreted by matured dendritic cells and M1-polarized macrophages, can depolymerize intracellular microtubules guiding activated STING trafficking towards lysosomes for degradation. Collectively, the dual-drug depots can initiate a long-lasting cascaded immunotherapy and chemotherapy, suppressing postsurgical tumor recurrence and metastasis.
研究领域:
肿瘤学
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免疫疗法
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药学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Jianhao Xie,Juan Su,Wanqi Zhou,Simin Cai,Wenfeng Liao,Jianing Zong,Junfeng Peng,Huanhuan Qu,Fei He,Kan Ding
Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant cancer with limited treatment options. Recent pharmacological studies suggested that Lamiophlomis rotata might contain components with antitumor activities. In this study, we aimed to investigate the potential of polysaccharides as active components in Lamiophlomis rotata . Our findings suggest that a polysaccharide, LRP01B, from Lamiophlomis rotata induces PDAC cells apoptosis by causing mitochondrial dysfunction and oxidative stress in vitro and in vivo . LRP01B is a homogeneous polysaccharide with a molecular weight of 15.9 kDa, composed of galactose, glucose, xylose, arabinose, rhamnose, and galacturonic acid in a molar ratio of 0.7: 0.3: 0.1: 1.1: 1.0: 4.3. The backbone of LRP01B mainly consists of 1,4-linked α-Gal p A, 1,2-linked α-Rha p , and 1,3-linked α-Gal p A, with existence of arabinose and xylose on the side chain. In vivo experiments demonstrate that LRP01B significantly inhibits pancreatic tumor growth in a patient-derived xenograft nude mouse model. Mechanism studies uncover that LRP01B induces apoptosis of PDAC cells through mitochondrial dysfunction and oxidative stress by recruiting TNF-related apoptosis-inducing ligand (TRAIL) to TRAIL-R1, which leads to the binding of LRP01B to both TRAIL and TRAIL-R1. Our results demonstrate that LRP01B is a dual-targeting polysaccharide with anti-PDAC activity and may be a promising anti-PDAC drug candidate.
研究领域:
癌症生物学
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药理学
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生物化学
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分子生物学
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药物化学
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DOI
PubMed
高影响因子
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
·
2014
·Vol. 20
·期 1
·109-121
·
IF 3.164
Zhang Zhongyu,Bi Caifeng,Fan Yuhua,Zhang Nan,Deshmukh Rahul,Yan Xingchen,Lv Xiuwen,Zhang Pengfei,Zhang Xia,Dou Q. Ping
Abstract Ubiquitin–proteasome system (UPS) plays a crucial role in many cellular processes such as cell cycle, proliferation and apoptosis. Aberrant activation of UPS may result in cellular transformation or other altered pathological conditions. Previous studies have shown that metal-based complexes could inhibit proteasome activity and induce apoptosis in certain human cancer cells. In the current study, we report that the cadmium and copper complexes with heterocycle-ornithine Schiff base are potent inhibitors of proteasomal chymotrypsin-like (CT-like) activity, leading to induction of apoptosis in cancer cells. Two novel copper-containing complexes and two novel cadmium-containing complexes with different heterocycle-ornithine Schiff base structures as ligands were synthesized and characterized. We found that complexes Cu1, Cd1 and Cd2 show proteasome-inhibitory activities in human breast cancer MDA-MB-231 and human prostate cancer LNCaP cells, resulting in the accumulation of p27, a natural proteasome substrate and other ubiquitinated proteins, followed by the induction of apoptosis. Our results suggest that metal complexes with heterocycle-ornithine Schiff base have proteasome-inhibitory capabilities and have the potential to be developed into novel anticancer drugs. Graphical Abstract
研究领域:
化学
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肿瘤学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
Acta Biomaterialia
·
2019
·
IF 6.638
Kang Chen,Xiu Xin,Lipeng Qiu,Wenpan Li,Guannan Guan,Gang Li,Mingxi Qiao,Xiuli Zhao,Haiyang Hu,Dawei Chen
P53 inactivation is often achieved through gene mutation and the excessive activity of its major negative regulator, murine double minute 2 protein (MDM2). In the present study we utilized a PAMAM-OH derivative (PAMSPF) to co-deliver p53 plasmid and MDM2 inhibitor (RG7388) to the tumor site and evaluated the synergistic anti-tumor effect of p53 plasmid and RG7388. PAMSPF was able to condense DNA and encapsulate RG7388 to form spherical nanoparticles (PAMSPF/p53/RG) with particle sizes of around 200 nm, and remain stable in the presence of heparin and nuclease . The drug loading capacity and encapsulation efficiency of RG7388 in PAMSPF/p53/RG were 0.5% and 92.5%, respectively. The p53 expressions in MDA-MB-435, p53-wild type MCF-7 cells (MCF-7/WT) and p53-silenced MCF-7 cells (MCF-7/S) treated with PAMSPF/p53/RG were promoted significantly. As a result, PAMSPF/p53/RG was able to inhibit cell proliferation , arrest cell cycle , and induce cell apoptosis of MDA-MB-435, MCF-7/WT and MCF-7/S cells. PAMSPF/p53/RG suppressed human umbilical vascular endothelial cells (HUVECs) migration, invasion and tube formation through decreasing the VEGF expression. And the biological activities described above of PAMSPF/p53/RG were significantly higher than those of PAMSPF/53 and PAMSPF/RG, exhibiting the synergistic actions of p53 plasmid and RG7388. In addition, intravenous administration of PAMPSF/p53/RG inhibited tumor growth of MDA-MB-435 and MCF-7/WT xenograft mice models, and induced no substantial weight loss. PAMSPF/p53/RG also reduced cell proliferation, and induced cell apoptosis in vivo based on the immunohistochemistry results. Collectively, PAMSPF/p53/RG is an excellent system for gene and drug co-delivery, and the combined treatment of p53 plasmid and RG7388 possesses a synergistic antitumor activity both in vitro and in vivo . Statement of significance In the present study we utilized a PAMAM-OH derivative (PAMSPF) to co-deliver p53 plasmid and RG7388 (MDM2 inhibitor) and evaluated their synergistic anti-tumor effect. PAMSPF could condense p53 plasmid and encapsulate RG7388 to form nanoparticles (PAMSPF/p53/RG). The p53 expressions in MDA-MB-435, p53-wild type MCF-7 cells (MCF-7/WT) and p53-silenced MCF-7 cells (MCF-7/S) treated with PAMSPF/p53/RG were promoted significantly. As a result, PAMSPF/p53/RG could inhibit cell proliferation, arrest cell cycle, and induce cell apoptosis of three kinds of cells. In addition, intravenous administration of PAMPSF/p53/RG inhibited tumor growth of MDA-MB-435 and MCF-7/WT xenograft mice models. Collectively, PAMSPF/p53/RG is an excellent system for gene and drug co-delivery, and the combined treatment of p53 plasmid and RG7388 possesses a synergistic antitumor activity.
研究领域:
癌症治疗
·
药学
·
纳米技术
·
分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Jingshuai Wang,Xuemin Gu,Yiqin Ouyang,Lei Chu,Mengjiao Xu,Kun Wang,Xiaowen Tong
Purpose Although the neutrophil membrane (NM)-based nanoparticulate delivery system has exhibited rapid advances in tumor targeting stemmed from the inherited instinct, the antitumor effect requires further improvement due to inefficient cellular internalization in the absence of specific interactions between NM-coated nanoparticles and tumor cells.Methods Herein, we fabricated drug-paclitaxel loaded NM camouflaging nanoparticles (TNM-PN) modified with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), favorable for the cellular internalization.Results The results showed that TNM-PN exerted a significant cytotoxicity to tumor cells by TRAIL-mediated endocytosis and strong adhesion to inflamed endothelial cells in vitro. Due to TRAIL modification as well as the adhesive interactions between neutrophil and inflamed tumor vascular endothelial cells, tumors in TNM-PN group exhibited almost 2-fold higher fluorescence intensities than that of NM camouflaging nanoparticles and 3-fold higher than that of bare nanoparticles, respectively. Significant tumor inhibition and survival rates of mice were achieved in TNM-PN group as a consequence of prolonged blood circulations to 48 h and preferential tumor accumulations, which was ascribed to targeting adhesion originated from NM to immune evasion and subsequent excellent cellular internalization.Conclusion The research unveiled a novel strategy of amplifying cellular internalization based on NM coating nanotechnology to boost antitumor efficacy.
研究领域:
药学
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纳米技术
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癌症研究
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2019
·
IF 7.901
Anwei Zhou,Junjie Du,Mengying Jiao,Daping Xie,Qianqian Wang,Lingjing Xue,Caoyun Ju,Zichun Hua,Can Zhang
The combined therapy of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and heat shock protein 70-targeting siRNA (siHSP70) has shown an improved anti-tumor effect on TRAIL-resistant tumor. However, vehicles to co-deliver these two biopharmaceuticals are challenging because of the distinct location of their targets on the cell surface and in the cytosol. Here we developed a hierarchically modular assembly formulation (TH-s-RSC) via the copper-free click reaction to co-encapsulate the positively-charged TRAIL and negatively-charged siHSP70 and release them in the extracellular space and cytoplasm. We demonstrate that TH-s-RSC can protect the packaged biopharmaceuticals through its hyaluronic acid shell in vivo , and sequentially release TRAIL in response to extracellular molecular including hyaluronidase (HAase) and matrix metalloproteinase 2 (MMP2), followed by the release of siHSP70 triggered by the reductive conditions in the cytoplasm. We showed that the complementary activity of TRAIL and siHSP70 exhibited superior synergistic anticancer efficacy in both A549 lung cancer xenograft models and 4T1 lung metastatic breast cancer models, compared to either treatment alone. Our strategy provides a promising platform for safe and effective co-delivery and dual-site targeting of biopharmaceuticals in cancer treatment that may be applicable in the future.
研究领域:
癌症治疗
·
生物制药
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纳米技术
·
药学
·
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）