JOURNAL OF INORGANIC BIOCHEMISTRY
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2020
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IF 3.212
Ying Wang,Qianqian Han,Feng Bai,Qiang Luo,Mingliang Wu,Gang Song,Hongmei Zhang,Yanqing Wang
In this work, the new polysaccharide-platinum conjugates of 5-aminosalicylic acid modified lycium barbarum polysaccharide linking platinum compounds were designed in order to construct an anticancer metal drug delivery system. The multiple analysis methods were used to describe the chemical structure and physical properties of the polysaccharide-metal conjugates . The results showed that 5-aminosalicylic acid successfully acted as linker which was covalently bound between polysaccharide and platinum compound. The morphology and rheological properties of polysaccharide have been changed by the formation of conjugates, which exhibited certain inhibition specificity to A549 (human lung cancer cell line). The agarose gel electrophoresis and fluorescence microscopy results demonstrated that such conjugates promoted the unwinding of DNA and could significantly damage the nucleus of A549 cells. Cell cycle analyzing the Pt complex of conjugates could cause intracellular DNA damage and induced G2 phase arrest . So, polysaccharide-platinum conjugates might find a range of applications, for example in metal anticancer drug delivery.
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
CHEMICO-BIOLOGICAL INTERACTIONS
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2022
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IF 5.168
Yudong Yin,Li Sun,Lixin Sheng,Liqiong Zhang,Jingjing Liu,Xiaoan Wen,Weibin Mo,Quande Wang,Keguang Cheng
In order to discover more effective and less toxic drugs in the field of anti-tumor, the backbone structure of 17 β -estradiol was modified, and 11 target compounds were synthesized. Compounds 5 and 10 , which exhibited better anti-tumor activity and higher selectivity (more than 10-fold), were chosen for further biological investigation. Flow cytometry results indicated that 5 and 10 could arrest MCF-7 cells in the G2 phase and induce apoptosis . Immunohistochemical analysis revealed that 5 and 10 could bind to the estradiol receptor alpha in MCF-7 cells. Western blotting and real-time PCR assays were performed to detect the effects of compounds on apoptosis-related targets at the protein and gene levels. These results showed that both 5 and 10 could dosed-dependently increase the expression of Apaf-1, Bax, caspase-3,8,9 and reduce the expression levels of the anti-apoptotic factors Bcl-2 and Bcl-xL. Besides, the Human apoptosis array assay demonstrated the expression level of death receptor Trail R2/DR5 was upregulated obviously while the expression of TNF R1, IAPs and Hsp27/60/70 were downregulated. On the whole, 5 induced MCF-7 cell death through the endogenous pathway in mitochondria and the exogenous pathway with death receptor Trail R2/DR5.
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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分子生物学
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产品关联
DOI
PubMed
高影响因子
FASEB JOURNAL
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2021
·Vol. 35
·期 10
·e21923
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IF 5.192
Peiling Wang,Xiangmei Hua,Yang Sun,Hongyu Li,Yuge Han Bryner,Richard P. Hsung,Jun Dai
Our recent studies have shown that haspin, a protein kinase imperative for mitosis, is engaged in the interphase progression of HeLa and U2OS cancer cells. In this investigation, we employed the Fucci reporter system and time-lapse imaging to examine the impact of haspin gene silencing on cell cycle progressions at a single-cell level. We found that the loss of haspin induced multiple cell cycle defects. Specifically, the S/G2 duration was greatly prolonged by haspin gene depletion or inhibition in synchronous HeLa cells. Haspin gene depletion in asynchronous HeLa and U2OS cells led to a similarly protracted S/G2 phase, followed by mitotic cell death or postmitotic G1 arrest. In addition, haspin deficiency resulted in robust induction of the p21 CIP1/WAF1 checkpoint protein, a target of the p53 activation. Also, co-depleting haspin with either p21 or p53 could rescue U2OS cells from postmitotic G1 arrest and partially restore their proliferation. These results substantiate the haspin's capacity to regulate interphase and mitotic progression, offering a broader antiproliferative potential of haspin loss in cancer cells.
研究领域:
癌症生物学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2015
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IF 3.65
Lejiao Jia,Zhenyu Li,Jingyi Shen,Dandan Zheng,Xiaona Tian,Hejian Guo,Ping Chang
The objective of the study is to fabricate multifunctional mesoporous silica nanoparticles for achieving co-delivery of conventional antitumor drug paclitaxel (PTX) and the multidrug resistance reversal agent tetrandrine (TET) expecting to overcome multidrug resistance of MCF-7/ADR cells. The nanoparticles were facile to prepare by self-assemble in situ drug loading approach. Namely, PTX and TET were solubilized in the cetyltrimethylammonium bromide (CTAB) micelles and simultaneously silica resources hydrolyze and condense to form nanoparticles. The obtained nanoparticles, denoted as PTX/TET-CTAB@MSN, exhibited pH-responsive release property with more easily released in the weak acidic environment. Studies on cellular uptake of nanoparticles demonstrated TET could markedly increase intracellular accumulation of nanoparticles. Furthermore, the PTX/TET-CTAB@MSN suppressed tumor cells growth more efficiently than only delivery of PTX (PTX-CTAB@MSN) or the free PTX. Moreover, the nanoparticle loading drugs with a PTX/TET molar ratio of 4.4:1 completely reversed the resistance of MCF-7/ADR cells to PTX and the resistance reversion index was 72.3. Mechanism research showed that both TET and CTAB could arrest MCF-7/ADR cells at G1 phase; and besides PTX arrested cells at G2 phase. This nanocarrier might have important potential in clinical implications for co-delivery of multiple drugs to overcome MDR.
研究领域:
纳米技术
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药物科学
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癌症研究
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药物递送系统
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生物医学工程
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2022
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IF 5.988
Sun Chao-Yue,Talukder Milton,Cao Di,Chen Cun-Wu
Abemaciclib is a cyclin-dependent kinases 4/6 (CDK4/6) inhibitor approved for the treatment of metastatic breast cancer. Preclinical studies suggest that abemaciclib has the potential for lung cancer treatment. However, several clinical trials demonstrate that monotherapy with abemaciclib has no obvious superiority than erlotinib to treat lung cancer patients, limiting its therapeutic options for lung cancer treatment. Here, we show that the US Food and Drug Administration (FDA)-approved drug, gilteritinib, enhances the cytotoxicity of abemaciclib through inducing apoptosis and senescence in lung cancer cells. Interestingly, abemaciclib in combination with gilteritinib leads to excessive accumulation of vacuoles in lung cancer cells. Mechanistically, combined abemaciclib and gilteritinib induces complete inactivation of AKT and retinoblastoma (Rb) pathways in lung cancer cells. In addition, RNA-sequencing data demonstrate that combination of abemaciclib and gilteritinib treatment induces G2 phase cell-cycle arrest, inhibits DNA replication, and leads to reduction in homologous recombination associated gene expressions. Of note, abemaciclib-resistant lung cancer cells are more sensitive to gilteritinib treatment. In a mouse xenograft model, combined abemaciclib and gilteritinib is more effective than either drug alone in suppressing tumor growth and appears to be well tolerated. Together, our findings support the combination of abemaciclib with gilteritinib as an effective strategy for the treatment of lung cancer, suggesting further evaluation of their efficacy is needed in a clinical trial.
研究领域:
肿瘤学
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药理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2022
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IF 16.744
Xiaoyang Liang,Ping Liu,Wen Li,Long Binh Vong,Tingting Wang,Lujing Geng,Yue Zhou,Siyu Wang,Qiang Lu,Fengping Tan,Xinxing Wang,Nan Li
Reactive oxygen species (ROS)-mediated cell cycle arrest mechanism shows distinguished potential for the inhibiting of cancer cells. However, poly ADP-ribose polymerase (PARP), an enzyme which can contribute to the repair of single-strand DNA nicks, largely limited the efficiency in cell cycle arrest. Here, polydopamine (PDA)/hyaluronic acid (HA) decorated and protein translation inhibitor homoharringtonine (HHT) loaded tellurium (Te)-prussian blue (PB) nanorods ( [email protected] @PDA-HA/HHT NRs) were synthesized for boosted G2 cell cycle arrest to realize tumor ablation. Under NIR-II irradiation, Te and Fe elements can collectively generate ROS and deplete GSH due to the fenton-like reaction and metal-reducing reaction under tumor microenvironment (TME), thus disturbing the DNA structure to induce cell cycle arrest. More importantly, HHT suppresses PARP production to induce DNA repair dysfunction, thereby boosting DNA oxidative damage. Remarkably, this nanoplatform degrades into ionic form under acid condition, illustrating inherently TME-responsive biodegradability. The anti-tumor evaluation illustrated that [email protected] @PDA-HA/HHT NRs could notably destroy tumor cells in both cellular experiments and mouse models. This study made a successful attempt in boosted cell cycle arrest and encouraged more biological explorations on biodegradation nanomaterials, especially in combating cancers.
研究领域:
癌症生物学
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纳米技术
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生物医学工程
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药学
✓ 已验证
产品关联
DOI
高影响因子
MEDICINAL CHEMISTRY RESEARCH
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2025
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IF 3.1
Wu Xinhua,Wu Lifang,Li Zhaoquan,Tian Wei,Li Tao
Three series of (dimethyl-, dibutyl-, and diphenyl-) new organotin(IV) complexes based on chlorine substituted aryl ligands were synthesized and characterized by UV, 1 H NMR, 13 C NMR, 119 Sn NMR, HRMS, and X-ray crystallography analysis. MTT results showed that chlorine substitution at different positions on the aryl group exhibited different anticancer activities. Among them, 5-chloro substituents > 3,5-dichloro substituents > 3-chloro substituents on the aryl ring of salicylaldehyde on Schiff base ligand. In addition, different substituents on the tin atom also demonstrated extreme differences in anticancer activities, where dibutyltin > diphenyltin > dimethyltin. Interestingly, the complex LTDB2 exhibited excellent anti-proliferative activity against breast cancer MDA-MB-231 cells (superior to cisplatin) and lower toxicity against human embryonic kidney HEK-293 cells in vitro. Flow cytometry showed that LTDB2 not only induced apoptosis, but also induced cell cycle arrest in G2 phase. These findings provide new insights for further research and development of novel organotin(IV) complexes as anticancer drugs. Complex LTDB2 exhibited excellent anti-proliferative activity against breast cancer MDA-MB-231 cells in vitro and was superior to cisplatin. Flow cytometry showed that LTDB2 not only induced apoptosis, but also induced cell cycle arrest in G2 phase.
研究领域:
化学
·
药理学
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肿瘤学
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材料科学
✓ 已验证
DOI
高影响因子
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