CHEMISTRY OF NATURAL COMPOUNDS
·
2018
·Vol. 54
·期 1
·106-111
·
IF 0.45
Huang Jia-yan,Yang Lin-dong,Su Chun-hua,Chu Xiang-wu,Zhang Jiang-yu,Deng Sheng-ping,Cheng Ke-guang
Using a reported pharmacophore, 4-[N,N-bis(2-chloroethyl)-amino]phenol, and pentacyclic triterpenes, pharmacologically and structurally diverse components of natural products, six pentacyclic triterpene-4-[N,N-bis(2-chloroethyl)-amino]phenol conjugates were synthesized by click chemistry. Their cytotoxicities against the BEL-7404 and NCI-H460 tumor cell lines were evaluated by the MTT assay. The in vitro results from the cytotoxicity assay indicated that at a compound concentration of 20 μM, these conjugates showed low toxicity (< 16%) toward the tested tumor cells in culture.
研究领域:
药理学
·
肿瘤学
·
有机化学
✓ 已验证
DOI
高影响因子
ONCOLOGY REPORTS
·
2020
·Vol. 43
·期 6
·1995-2003
·
IF 3.417
Li Lv,Wenhui Zhang,Tingting Li,Lifeng Jiang,Xinyan Lu,Jie Lin
Hispidulin is a medicinal natural compound isolated from S. involucrata, which exhibits potent anticancer properties. However, there are few reports on its effects on lung cancer cells. Therefore, the current study investigated the effects of hispidulin on cell viability and apoptosis in human non‑small‑cell lung cancer (NSCLC) cell lines NCI‑H460 and A549 in vitro and in vivo. Methyl thiazolyl tetrazolium, colony formation assay, Hoechst 33342 staining, flow cytometry and western blotting were performed on Human NCI‑H460 and A549 cells. A mouse xenograft model was also established using NCI‑H460 cells. The results showed that the growth of NCI‑H460 and A549 cells was inhibited, while apoptosis was promoted by hispidulin via increased generation of reactive oxygen species (ROS) in a dose‑dependent manner. Furthermore, hispidulin triggered apoptosis in NSCLC cells through upregulating the expression of cleaved caspase‑3 and cleaved poly [ADP‑ribose] polymerase. All these effects were reversed upon pretreatment with glutathione, a selective ROS inhibitor. In addition, endoplasmic reticulum stress (ER stress) in NCI‑H460 cells was activated by hispidulin. Pretreatment with tauroursodeoxycholic acid, a specific ER stress inhibitor, effectively reduced the cell apoptosis induced by hispidulin. In conclusion, hispidulin induces ROS‑mediated apoptosis via activating the ER stress pathway. The current study provides theoretical basis for the antitumor effect of hispidulin in NSCLC.
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
Journal of Materials Chemistry B
·
2014
·Vol. 3
·期 1
·119-126
·
IF 0
Yinan Zhao,Shubiao Zhang,Yuan Zhang,Shaohui Cui,Huiying Chen,Defu Zhi,Yuhong Zhen,Shufen Zhang,Leaf Huang
Several novel tri-peptide cationic lipids were designed and synthesized for delivering DNA and siRNA. They have tri-lysine and tri-ornithine as headgroups, a carbamate group as a linker and 12 and 14 carbon atom alkyl groups as tails. These tri-peptide cationic lipids were prepared into cationic liposomes for the study of the physicochemical properties and gene delivery. Their particle size, zeta potential and DNA-binding were characterized to show that they were suitable for gene transfection. Further results indicate that these lipids can transfer DNA and siRNA very efficiently into NCI-H460 and Hep-2 tumor cells. The selected lipid, CDO14, was able to deliver combined siRNAs against c-Myc and VEGF for silencing distinct oncogenic pathways in lung tumors of mice, with little in vitro and in vivo toxicity.
研究领域:
药学
·
分子生物学
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
Oncotarget
·
2016
·
IF 5.008
Lanmei Chen,Guodong Li,Fa Peng,Xinming Jie,Guangzhi Dongye,Kangrong Cai,Ruibing Feng,Baojun Li,Qingwang Zeng,Kaiyi Lun,Jincan Chen,Bilian Xu
In the present study, it was found that the ruthenium (II) imidazole complex [Ru(Im) 4 (dppz)] 2+ (Ru1) could induce significant growth inhibition and apoptosis in A549 and NCI-H460 cells. Apart from the induction of apoptosis, it was reported for the first time that Ru1 induced an autophagic response in A549 and NCI-H460 cells as evidenced by the formation of autophagosomes, acidic vesicular organelles (AVOs), and the up-regulation of LC3-II. Furthermore, scavenging of reactive oxygen species (ROS) by antioxidant NAC or Tiron inhibited the release of cytochrome c , caspase-3 activity, and eventually rescued cancer cells from Ru1-mediated apoptosis, suggesting that Ru1 inducing apoptosis was partially caspase 3-dependent by triggering ROS-mediated mitochondrial dysfunction in A549 and NCI-H460 cells. Further study indicated that the extracellular signal-regulated kinase (ERK) signaling pathway was involved in Ru1-induced autophagy in A549 and NCI-H460 cells. Moreover, blocking autophagy using pharmacological inhibitors 3-methyladenine (3-MA) and chloroquine (CQ) enhanced Ru1-induced apoptosis, indicating the cytoprotective role of autophagy in Ru1-treated A549 and NCI-H460 cells. Finally, the in vivo mice bearing A549 xenografts, Ru1 dosed at 10 or 20 mg/kg significantly inhibited tumor growth.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2019
·
IF 3.131
Chuanmin Zhang,Shubiao Zhang,Defu Zhi,Yinan Zhao,Shaohui Cui,Jingnan Cui
This work designed a new delivery system (L-PTX-PSur), which could efficiently co-deliver paclitaxel (PTX) and survivin siRNA (Sur) to overcome the dose-limiting toxicity by effectively accumulating PTX in tumor and obtain enhanced therapy by synergistic effect. In this co-delivery system, protamine was selected to condense siRNA into a compacted ‘core’, and a carbamate-linked cationic lipid was used to develop PTX-loaded liposome to entrap the core. L-PTX-PSur with protamine could facilitate Sur entry into NCI-H460 cells and exhibited high encapsulation efficiency of PTX. In vitro studies on the NCI-H460 lung cancer cells revealed that L-PTX-PSur offered significant advantages over the control groups, and it had the highest cellular uptake, the lowest cell viability and the strongest apoptosis. Western blot result showed that survivin protein expression could be noticeably suppressed by L-PTX-PSur in NCI-H460 cells. And the down-regulation of survivin protein could lower the apoptotic threshold of cancer cells and render PTX more effective with low doses. Collectively, L-PTX-PSur with a low dose of PTX could induce a synergistic inhibitory effect on cancer cells growth by the collaboration of PTX and Sur. This work provides a promising strategy for the treatment of lung cancer.
研究领域:
肿瘤学
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF INTERNATIONAL MEDICAL RESEARCH
·
2022
·
IF 1.573
Wen Zhao,Ye Xu,Qingkui Guo,Wenliang Qian,Chen Zhu,Min Zheng
ObjectiveTo synthesize a novel chalcone-1,3,4-thiadiazole hybrid and investigate its anticancer effects against NCI-H460 cells.Methods(E)-3-(4-bromophenyl)-1-(4-hydroxyphenyl)prop-2-en-1-one, 1,3-dibromopropane and 1,3,4-thiadiazole-2-thiol were used as chemical materials to synthesize compound ZW97. The NCI-H460 lung cancer cell line was selected to explore the antitumor effects of compound ZW97 in vitro and in vivo.ResultsCompound ZW97 selectively inhibited cell proliferation against lung cancer cell lines NCI-H460, HCC-44 and NCI-H3122 with IC50 values of 0.15 μM, 2.06 μM and 1.17 μM, respectively. ZW97 suppressed migration and the epithelial–mesenchymal transition process in NCI-H460 cells in a concentration-dependent manner. Based on the kinase activity results and docking analysis, compound ZW97 is a novel tyrosine-protein kinase Met (c-Met kinase) inhibitor. It also inhibited NCI-H460 cell growth in xenograft models without obvious toxicity to normal tissues.ConclusionsCompound ZW97 is a potential c-Met inhibitor that might be a promising agent to treat lung cancer by inhibiting the epithelial–mesenchymal transition process.
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
JOURNAL OF INORGANIC BIOCHEMISTRY
·
2024
·
IF 3.8
Wujiu Jiang,Qing Luo,Wei Huang,Yuxing Tan,Yiyuan Peng
Diorganotin acylhydrazone complexes with mitochondrial targeting demonstrate significant potential as replacements for platinum-based complexes due to their potent anticancer properties. Twelve methylphenyltin arylformylhydrazone complexes have been synthesized by microwave “one-pot” reaction. The complexes have been characterized by FT-IR, multinuclear NMR ( 1 H, 13 C, and 119 Sn), TGA, and HRMS. Crystal structures were determined for 10 out of the 12 complexes under study. Structures 1 through 8 , 10 and 12 possessed a central symmetric structure of a di-nuclear Sn 2 O 2 tetrahedral ring. All complexes were tested for their inhibitory activity against human cell lines NCI-H460, MCF-7, and HepG2. Complex 8 exhibited the most effective inhibitory effect on HepG2 cells, with an IC 50 value of 1.34 ± 0.04 μM. Preliminary studies on the anticancer mechanism suggest that complex 8 induces apoptosis in HepG2 cells via the mitochondrial pathway, accompanied by G2/M phase cell cycle arrest.
研究领域:
无机化学
·
药物化学
·
癌症研究
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2020
·
IF 5.573
Jincan Chen,Jie Wang,Yuanyuan Deng,Baojun Li,Chengpeng Li,Yuxue Lin,Dongbin Yang,Huanyun Zhang,Lanmei Chen,Tao Wang
Two novel cyclometalated Ru(II) complexes containing isoquinoline ligand, [Ru(bpy) 2 (1-Ph-IQ)](PF 6 ), (bpy = 2,2′-bipyridine; 1-Ph-IQ = 1-phenylisoquinoline; RuIQ-1 ) and [Ru(phen) 2 (1-Ph-IQ)](PF 6 ) (phen = 1,10-phenanthroline; RuIQ-2 ) were found to show high cytotoxic activity against NCI–H460, A549, HeLa and MCF-7 cell lines. Notably, both of them exhibited IC 50 values that were an order of magnitude lower than those of clinical cisplatin and two structurally similar Ru(II)-isoquinoline complexes [Ru(bpy) 2 (1-Py-IQ)](PF 6 ) 2 ( Ru3 ) and [Ru(phen) 2 (1-Py-IQ)](PF 6 ) 2 ( Ru4 ) (1-Py-IQ = 1-pyridine-2-yl). The cellular uptake and intracellular localization displayed that the two cyclometalated Ru(II) complexes entered NCI–H460 cancer cells dominantly via endocytosis pathway, and preferentially distributed in the nucleus. Further investigations on the apoptosis-inducing mechanisms of RuIQ-1 and RuIQ-2 revealed that the two complexes could cause S, G2/M double-cycle arrest by regulating cell cycle related proteins. The two complexes also could reduce the mitochondrial membrane potential (MMP), promote the generation of intracellular ROS and trigger DNA damage, and then lead to apoptosis-mediated cell death . More importantly, RuIQ-2 exhibits low toxicity both towards normal HBE cells in vitro and zebrafish embryos in vivo . Accordingly, the developed complexes hold great potential to be developed as novel therapeutics for effective and low-toxic cancer treatment.
研究领域:
化学
·
药学
·
肿瘤学
·
细胞生物学
·
毒理学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）