MOLECULES
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2023
·Vol. 28
·期 5
·2357
·
IF 4.6
Tianxiao Zhou,Kaige Yang,Jin Huang,Wenchang Fu,Chao Yan,Yan Wang
Lung cancer is the most common primary malignant lung tumor. However, the etiology of lung cancer is still unclear. Fatty acids include short-chain fatty acids (SCFAs) and polyunsaturated fatty acids (PUFAs) as essential components of lipids. SCFAs can enter the nucleus of cancer cells, inhibit histone deacetylase activity, and upregulate histone acetylation and crotonylation. Meanwhile, PUFAs can inhibit lung cancer cells. Moreover, they also play an essential role in inhibiting migration and invasion. However, the mechanisms and different effects of SCFAs and PUFAs on lung cancer remain unclear. Sodium acetate, butyrate, linoleic acid, and linolenic acid were selected to treat H460 lung cancer cells. Through untargeted metabonomics, it was observed that the differential metabolites were concentrated in energy metabolites, phospholipids, and bile acids. Then, targeted metabonomics was conducted for these three target types. Three LC-MS/MS methods were established for 71 compounds, including energy metabolites, phospholipids, and bile acids. The subsequent methodology validation results were used to verify the validity of the method. The targeted metabonomics results show that, in H460 lung cancer cells incubated with linolenic acid and linoleic acid, while the content of PCs increased significantly, the content of Lyso PCs decreased significantly. This demonstrates that there are significant changes in LCAT content before and after administration. Through subsequent WB and RT-PCR experiments, the result was verified. We demonstrated a substantial metabolic disparity between the dosing and control groups, further verifying the reliability of the method.Keywords:H460 lung cancer cells;short-chain fatty acids;polyunsaturated fatty acids;untargeted metabolism;targeted metabolism
研究领域:
肿瘤学
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代谢组学
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细胞生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2026
·
IF 8.5
Xin-xin Yang,Si-qi Zhang,Ya-long Chen,Cui-xia Ma,Wei Lv,Fen-li He,Ke Guo,Qiao Zhang,Yu-wei Wang,Hao Yan,Ting-ting Zhang,Peng Zhao
In this study, a novel polysaccharide (TGT-S) was successfully extracted from the medicinal residue of Marsdenia tenacissima (Roxb.) Wight et Arn. To enhance its anti-lung cancer efficacy and exploit the therapeutic potential of selenium nanoparticles (SeNPs), we developed TGT-S-functionalized SeNPs (TGTs-SeNPs). The nanocomposites were systematically characterized in terms of size, morphology, structural features, colloidal stability, and thermal properties using multiple analytical techniques. Through response surface methodology optimization, TGTs-SeNPs with uniform spherical morphology and narrow size distribution were obtained, exhibiting an average particle size of 128.96 nm. The optimized synthesis parameters were established as follows: selenium-to-polysaccharide mass ratio of 1:5.483, selenium-to-ascorbic acid molar ratio of 1:4.213, selenite concentration of 9.474 mM, and reaction time of 4.175 h. The resulting TGTs-SeNPs demonstrated remarkable stability under physiological and alkaline conditions. The anti-cancer mechanism of TGTs-SeNPs (4.5–18 μg/mL) was elucidated in H460 lung cancer cells. The nanoparticles significantly inhibited cell proliferation by inducing S-phase cell cycle arrest and promoting apoptosis, as determined by flow cytometry. WB and RT-qPCR analysis further confirmed this dual mechanism, revealing downregulation of key cell cycle regulators (Cyclin A/D and CDK2/4) and activation of the mitochondrial apoptotic pathway, characterized by an increased Bax/Bcl-2 ratio and caspase-3 activation. This study not only presents a sustainable strategy for utilizing Marsdenia tenacissimaresidue but also highlights the promise of polysaccharide-based nanodrugs in cancer therapy.
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高影响因子
CHEMISTRY OF NATURAL COMPOUNDS
·
2018
·Vol. 54
·期 1
·106-111
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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
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肿瘤学
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有机化学
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DOI
高影响因子
Medicinal Chemistry
·
2017
·Vol. 13
·期 8
·753-760
·
IF 2.331
Guo Ping,Xie Zixin,Zhang Huan,Zhang Zaikui,Han Chao,Cheng Donghua,Lin Dan,Zhang Yuan,Wang Xuebao,Guo Xin,Ye Faqing
Background: Thienopyrimidinone is a newly designed, selective fibroblast growth factor receptor 1 (FGFR1) inhibitor with an excellent anticancer effect. Objective: The goal of the present study was to design and synthesize better FGFR1 inhibitors through modifications of the lead
compound thienopyrimidinone. Methods: In the present study, a series of C-2 substituted derivatives of thienopyrimidinone, namely L1-L16, were synthesized, and their inhibitory effects on FGFR1 were evaluated. The anti-proliferative activities of these compounds were assessed by MTT assay.
Results: Among the novel derivatives, L11 was found to exert remarkable FGFR1 inhibitory activity (79.93% at 10 μM) and anti-proliferative activity, with IC50 values of 2.1, 2.5, and 3.5 µM in the FGFR1-overexpressing cell lines, H460, HT-1197, and B16F10, respectively.
Conclusion: Our newly synthesized thienopyrimidinone derivatives may be candidate FGFR1 inhibitors for future development as novel anticancer agents.
研究领域:
药理学
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肿瘤学
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药物化学
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PubMed
高影响因子
JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
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2014
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IF 0.968
Ping Guo,Yue-Wu Wang,Bi-Xia Weng,Xiao-Kun Li,Shu-Lin Yang,Fa-Qing Ye
Using curcumol that was extracted from the volatile oil of Rhizoma Curcumae as the raw material, its derivatives were synthesized and purified. The structures of these compounds were confirmed by 1H, 13C NMR, and mass spectral data. The test compounds were evaluated for their in vitro anti-tumor activity against gastric cancer cell lines SGC-7901 and lung carcinoma cell line H460 by methyl thiazolyl tetrazolium chromatometry. Distinct structure–activity relationships of these curcumol derivatives were also revealed for inhibiting cell proliferation. Presence of electron-withdrawing groups or amino could increase the activity significantly, whereas esterification of 8-hydroxy diminished the anti-tumor activity. Many of the tested candidates exhibited higher inhibition efficiency than curcumol, suggesting that structural modifications could enhance its activity effectively.
研究领域:
药理学
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化学
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肿瘤学
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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
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分子生物学
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癌症研究
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PubMed
ONCOLOGY REPORTS
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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
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药理学
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细胞生物学
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PubMed
高影响因子
Frontiers in Pharmacology
·
2021
·
IF 5.811
Jiahui Ye,Longfei Mao,Luoyijun Xie,Rongjun Zhang,Yulin Liu,Lizeng Peng,Jianxue Yang,Qingjiao Li,Miaomiao Yuan
Chemotherapy is the most common clinical treatment for non-small cell lung cancer (NSCLC), but low efficiency and high toxicity of current chemotherapy drugs limit their clinical application. Therefore, it is urgent to develop hypotoxic and efficient chemotherapy drugs. Theophylline, a natural compound, is safe and easy to get, and it can be used as a modified scaffold structure and hold huge potential for developing safe and efficient antitumor drugs. Herein, we linked theophylline with different azide compounds to synthesize a new type of 1,2,3-triazole ring-containing theophylline derivatives. We found that some theophylline1,2,3-triazole compounds showed a good tumor-suppressive efficacy. Especially, derivative d17 showed strong antiproliferative activity against a variety of cancer cells in vitro, including H460, A549, A2780, LOVO, MB-231, MCF-7, OVCAR3, SW480, and PC-9. It is worth noting that the two NSCLC cell lines H460 H and A549 are sensitive to compound d17 particularly, with IC50 of 5.929 ± 0.97 μM and 6.76 ± 0.25 μM, respectively. Compound d17 can significantly induce cell apoptosis by increasing the ratio of apoptotic protein Bax/Bcl-2 by downregulating the expression of phosphorylated Akt protein, and it has little toxicity to normal hepatocyte cells LO2 at therapeutic concentrations. These data indicate that these theophylline acetic acid-1,2,3-triazole derivatives may be potential drug candidates for anti-NSCLC and are worthy of further study.
研究领域:
肿瘤学
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药物化学
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药理学
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DOI
PubMed
高影响因子
Oncotarget
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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
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药理学
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细胞生物学
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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
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药学
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分子生物学
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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
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药理学
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细胞生物学
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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
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药物化学
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癌症研究
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药学
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）