SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2016
·
IF 2.653
Li-Na Wen,Meng-Xia Xie
KRAS promoter can form G-quadruplex structure and regulate gene transcription. The drugs which can bind with G-quadruplex of KRAS promoter may be potential remedy for treatment of cancers associated with KRAS mutation. The interaction mechanism between the G-quadruplex of KRAS promoter and three isoquinoline alkaloids (jatrorrhizine, berberine and sanguinarine) has been investigated by UV-visible, fluorescence and circular dichroism spectroscopic methods. The results showed that the three alkaloids can form complexes with G-quadruplex KRAS promoter with the molecular ratio of 1:1, and the binding constants were (0.90 ± 0.16) × 10 6 L mol − 1 , (0.93 ± 0.21) × 10 6 L mol − 1 and (1.16 ± 0.45) × 10 6 L mol − 1 for jatrorrhizine , berberine and sanguinarine . The absorption spectra, KI quenching and fluorescence anisotropy and polarization studies suggested jatrorrhizine and berberine interacted with G-quadruplex by not only end-stacking binding mode but also grooves or loops binding mode, while sanguinarine by end-stacking binding mode. Sanguinarine was more beneficial to maintain the stability and parallel conformation of KRAS promoter G-quadruplex. MTT assay was performed to evaluate antiproliferation effects of the three isoquinoline alkaloids on SW620 cells, and the antiproliferation effects of the three alkaloids were sanguinarine > berberine > jatrorrhizine. All the three alkaloids can bind with KRAS promoter G-quadruplex, and sanguinarine had the better binding property and antiproliferation effects on SW620 cells. The results obtained are meaningful to explore potential reagents targeting the parallel G-quadruplex structure of KRAS promoter for gene theraphy of colorectal carcinomas.
研究领域:
分子生物学
·
癌症研究
·
药理学
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
Botanical Studies
·
2014
·Vol. 55
·期 1
·1-8
·
IF 0.809
Lin Jian,Li Xican,Han Lu,Li Fei,Lu Wenbiao,Bai Ye,Chen Dongfeng
Background In the study, Folium Sennae (FS) was firstly extracted by various solvents to obtain five FS extracts. Then, five FS extracts were evaluated for the protective effects against •OH-induced DNA damage, antioxidant abilities in vitro, and chemical contents using various methods. On this basis, the correlation graphs between the pharmacological effects and chemical contents were plotted to obtain the correlation coefficients (R values). Finally, in order to obtain biological evidence, ethyl acetate extract of FS (EAFS) was investigated for the protective effect against •OH-induced MSCs (mesenchymal stem cells) damage using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl) assay. Results The pharmacological assays indicated that five FS extracts could effectively protect against •OH-induced DNA damage. The correlation analysis suggested that the average R values of total phenolics, total anthraquinones, aloe-emodin, rhein, and emodin were respectively 0.843, 0.833, 0.753, 0.820, and 0.784, while those of total sugars and total saponins were respectively 0.103 and 0.0068. The mechanistic analysis revealed that five FS extracts could also scavenge •OH, •O 2 – , DPPH• & ABTS• + radicals, and reduce Cu 2+ to Cu + . MTT assay revealed that the viability of MSCs which were treated with •OH radicals has been effectively protected by EAFS (3 and 30 μg/mL). Conclusion On this basis, it can be concluded that: ( i ) Folium Sennae exhibits a protective effect against •OH-induced damages to DNA and MSCs; ( ii ) The effects may be attributed to phytophenols (especially aloe-emodin, rhein, and emodin), not sugars or saponins; ( iii ) They exert the protective action via hydrogen atom transfer (HAT) and/or sequential electron proton transfer (SEPT) mechanisms which make phenolic –OH moiety be oxidized to stable semi-quinone form; ( iv ) The stability of semi-quinone form can ultimately be responsible for the protective or antioxidant effect of phytophenols.
研究领域:
药理学
·
生物化学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
MEDICAL SCIENCE MONITOR
·
2020
·
IF 1.918
Yan Dong,Jun Yang,Liyuan Yang,Ping Li
Background Quercetin (Que) is reported to induce apoptosis of lung cancer cells. Src is closely related to the progression of non-small cell lung cancer (NSCLC) and can be modulated by Que in macrophages. In the current study, the interaction between Que and Src signaling in NSCLC cells was explored to explain the anti-NSCLC function of Que. Material/Methods NSCLC cell line HCC827 was subjected to the administrations of Que at different concentrations. The effect of Que on tumor cell proliferation was detected using MTT and colony formation assays. Then the effect on the migration and invasion abilities was assessed using scratch and Transwell assays. At molecular level, the changes in Src/Fn14/NF-κB signaling were determined using western blotting assays. The role of Src in the function of Que was further explored by inducing the expression of Src gene in NSCLC cells before Que administration. The results of the in vitro assays were verified using a NSCLC mice model. Results Que inhibited the proliferation and anchorage-independent growth of NSCLC cells. Additionally, Que delayed in the gap closure rate in scratch assays and decreased the membrane-penetrating cell number in Transwell assays. At a molecular level, Que suppressed the expression of Src, which subsequently inhibited Fn14/NF-κB signaling. In in vivo assays, Que inhibited the growth of solid tumors. After the overexpression of Src in NSCLC cells, the anti-NSCLC effect of Que was blocked by inducing NSCLC proliferation and metastasis, and by activating Fn14/NF-κB signaling. Moreover, the induced level of Src promoted the growth and metastasis potential of solid tumors in mice. Conclusions Que exerted the anti-NSCLC effect by inhibiting Src-mediated Fn14/NF-κB pathway both in vitro and in vivo .
研究领域:
肿瘤学
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药理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ChemNanoMat
·
2021
·Vol. 7
·期 12
·1361-1368
·
IF 3.154
Zhaoyu Han,Yue Qian,Yiyang Wu,Yanfei Cai,Jian Jin,Zhaoqi Yang
Graphical A hybrid drug delivery system based on ZIF-90 encapsulated with Doxorubicin and Ce6-G3139 has been established to induce apoptosis for enhanced chemotherapy. Metal-organic frameworks are highly porous and biodegradable and have found numerous applications in biomedicine. However, the traditional chemotherapy of MOF-drug delivery system remains a great challenge because of adverse side effects and cell tolerance. In this work, we have fabricated a hybrid drug delivery system based on ZIF-90 encapsulated with Doxorubicin (DOX) and Ce6-G3139 for enhanced chemotherapy. The released DOX can enter cell nucleus and trigger cell death. In addition, the G3139 binds to the anti-apoptotic gene Bcl-2 in tumor cells and related proteins are downregulated to inhibit cell proliferation. Meanwhile, the photosensitizer Ce6 carried by the nucleic acid will generate abundant reactive oxygen species under a near-infrared (NIR) laser irradiation thus induces more cell apoptosis. It was worth mentioning that in vitro MTT test in the MCF-7 cells assays revealed that DOX@ ZIF-90/Ce6-G3139 nanoparticles possessed stronger anticancer capability than free DOX or DOX@ ZIF-90 nanoparticles indicating that the investigation offers an exciting new therapeutic strategy for the treatment of chemotherapy.
研究领域:
生物医学工程
·
癌症治疗
·
纳米技术
·
药学
✓ 已验证
产品关联
DOI
高影响因子
INORGANIC CHEMISTRY
·
2022
·
IF 5.436
Yuhao Wu,Yirong Wang,Yun Sun,Zhen Li,Xianghong Li,Zhiguo Zhou,Dingguo Tang
A novel family of ruthenium nitrosyl complexes [Ru(bpy)(C∧N)(MeCN)NO](PF6)2 (2a–2e, bpy = 2,2′-bipyridine, HC∧N = 2-phenylpyridine and its derivatives) has been prepared by reacting cyclometalated ruthenium complexes [Ru(bpy)2(C∧N)][PF6] (1a–1e) with NO+, which were comprehensively characterized by mass, IR, NMR, and UV–vis spectra as well as the single-crystal X-ray structure determinations. Herein, the coordination geometry of Ru atoms in 2a–2e is a distorted octahedron and {RuII–NO+}6 is present in these complexes. Theoretical calculations suggest that the reactions involving dissociation of one bipyridine and coordination with NO+ proceed spontaneously (ΔG < 0) and the transformation from 1a–1e to the intermediates is dominated by substituents (ΔGRI varies from −1.19 to −1.53 eV), which influence the binding energy between Ru(II) and NO+ in complexes 2a–2e (−89.42 to −101.17 kcal/mol) and thus control the photorelease of NO on a certain scale. The weak absorption bands in the visible region could be attributed to the contribution of dπ(RuII) → π*(NO+), which were enhanced greatly under light, indicating the possible release of NO. The photoinduced NO, as well as singlet oxygen (1O2), was then confirmed by EPR spectra, and the amount of NO released from 2a–2e was estimated via Griess reagent assay. The cytotoxicity of these complexes with or without visible light irradiation was also investigated using an MTT assay.
研究领域:
无机化学
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配位化学
·
光化学
·
生物化学
✓ 已验证
DOI
高影响因子
Journal of Biobased Materials and Bioenergy
·
2022
·Vol. 16
·期 1
·117-126
·
IF 0.687
Feng Nianjie,She Shaowen,Hu Chuanqin,Wu Qian
To find new plant-derived antitumor drugs, hydrolysate and fractions of poplar were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for their inhibitory effect against liver cancer HepG-2 cells. Strong cytotoxicity of hydrolysate was revealed at
processing temperature of 180 °C or above. The hydrolysate formed at 180 °C was sequentially extracted using organic solvent to obtain five fractions, and only the diethyl ether-soluble fraction (F
De) showed specific cytotoxicity. The eluted fraction of acetone/n-hexane
(F
1) was further isolated by column chromatography separation from the F
De fraction at a yield of 70%, and could severely decrease cell viability. LC-MS chromatography indicated that 5-hydroxymethyl furfural, ρ-hydroxybenzoic acid and syringaldehyde
were the main compounds in the F
1 fraction. Furthermore, the results of flow cytometry, Western blotting, and polymerase chain reaction indicated that syringaldehyde could tightly control the growth and metabolism of HepG-2 cells. The findings could move forward the value-added
applications of lignocellulosic hydrolysate on traditional medicines.
研究领域:
植物学
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遗传学
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肿瘤学
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药理学
·
分析化学
✓ 已验证
DOI
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2023
·
IF 3.8
Huiling Zhou,Chenxin Duan,Huimin Qin,Chaonan Huang,Jingxuan Hou,Yanming Chen,Jin Zhu,Cangcang Xu,Jian Jin,Tao Zhuang
ABSTRACT Palbociclib (PAL), a highly selective inhibitor of cell cycle protein-dependent kinases (CDK) 4/6, is primarily used for treating advanced breast cancer. However, the use of PAL has been limited by its poor tabletability and dose-related toxic side effects. In this study, to improve the tabletability of PAL and reduce its effective dose, a flavonoid–kaempferol (KAE) was selected as the coformer to synthesize cocrystal with PAL. The novel cocrystal PAL-KAE was prepared by antisolvent cocrystallization and characterized by various techniques including X-ray diffraction (SCXRD and PXRD), thermal analysis (DSC and TG), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), Hirshfeld surface (HS), HOMO−LUMO analysis, and molecular electrostatic potential (MEP). Powder compaction experiments indicated that PAL-KAE cocrystal significantly improved the tabletability of PAL. The cytotoxicity test suggested that PAL-KAE also exerted synergistic antitumor effect against human ovarian cancer cell line OVCAR3 in MTT assay. Docking results indicated that PAL-KAE had lower binding energy with CDK 6 than PAL. Furthermore, the cocrystal PAL-KAE exhibits excellent stability in long-term testing, accelerated testing and stressing test. This paper provides a promising strategy for improving the tabletability of PAL and enhancing its anticancer activity, thus reducing the dose-related side effects of PAL.
研究领域:
药学
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材料科学
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癌症研究
·
药物递送
✓ 已验证
产品关联
DOI
高影响因子
Molecular Medicine Reports
·
2015
·Vol. 12
·期 3
·3869-3873
·
IF 1.554
Shi‑Min Yu,Dong‑Hui Hu,Jian‑Jun Zhang
Hepatocellular carcinoma (HCC) is a highly malignant tumor, associated with poor patient prognoses, and high rates of morbidity and mortality. To date, the therapeutic strategies available for the treatment of HCC remain limited. The present study aimed to elucidate the anticancer activity of umbelliferone, a naturally occurring coumarin derivative isolated from Ferula communis, against the HepG2 HCC cell line. A 3‑(4,5‑dimthylthaizol‑2‑yl)‑2,5, diphenyltetrazolium bromide assay was used to evaluate cell viability following umbelliferone treatment, and the effects of umbelliferone on cell cycle progression and apoptosis were evaluated using flow cytometry. The presence of morphological features characteristic of apoptosis, including cell shrinkage, membrane blebbing, nuclear condensation and apoptotic body formation, were evaluated in HepG2 cells following umbelliferone treatment. Cell cycle analysis conducted via propidium iodide (PI) staining indicated that umbelliferone treatment induced cell cycle arrest at S phase in HepG2 cells. Analysis with Annexin V and PI staining revealed that umbelliferone induced apoptotic events in HepG2 cells in a concentration‑dependant manner (0‑50 µM). Umbelliferone also induced dose‑dependant DNA fragmentation. In conclusion, umbelliferone was found to exhibit significant anticancer effects via the induction of apoptosis, cell cycle arrest and DNA fragmentation in HepG2 cancer cells.
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
CHEMISTRY & BIODIVERSITY
·
2018
·Vol. 15
·期 4
·e1800024
·
IF 1.617
Qi-Zhe Gong,Di Xiao,Feng Feng,Xiao-Dong Wen,Wei Qu
ent -Sauchinone, a lignan isolated from Saururus chinensis ( Lour .) Baill ., was reported that it could modulate the expression of signal transducer and activator of transcription 3 (STAT3). Since STAT3 plays a key role in invasion, migration, and metastasis of cancer, we investigated whether ent -sauchinone could exert promising inhibitory effects on the invasion and migration of the metastatic human liver cancer cell line SMMC-7721 in the present study. ent -Sauchinone was extracted from dried herbs of Saururus chinensis ( Lour .) Baill . Human liver cancer cell lines SMMC-7721 and HCCLM3 were used to test the effect of ent -sauchinone on cell viability. The IC 50 values and time-dependent effect of ent -sauchinone were determined by MTT assay. Cell migration and invasion of SMMC-7721 were evaluated by the wound healing test and transwell assay respectively, the known anti-metastasis agent curcumin was used as a positive control. Western blotting assay was used to investigate relevant molecular mechanisms of cell invasion and migration. Though ent -sauchinone didn't show high cytotoxicity, the wound healing assay and transwell migration assay revealed a profound impairment in the metastatic potential of SMMC-7721 cells due to down-regulation of N-cadherin, MMP-2, and MMP-9 proteins induced by inhibiting the phosphorylation of STAT3. These findings suggest that ent -sauchinone could be used as a promising agent to treat cancer metastasis.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Omega
·
2023
·
IF 4.1
Yimei Tang,Kuan Yang,Siyu Zhao,Qingqing Chen,Lan Qin,Bei Qin
To solve the problems associated with poorly water-soluble nonsteroidal anti-inflammatory drugs (NSAIDs), naproxen-based ionic liquids (ILs) containing naproxen as an active pharmaceutical ingredient (API) anion were prepared with benzalkonium (tetradecyldimethylbenzyl ammonium), choline, and 1-octyl-3-methylimidazole as the cation. The structures and thermal properties were analyzed. Through the conductivity method, the solubility at 25 and 37 °C and the critical micelle concentration (CMC) at 25 °C were determined in water and ethanol. The octanol–water partition coefficients (Kow) at 25 °C were measured with the shake-flask method. The cytotoxicity was evaluated with the MTT method. The results showed that the conversion of naproxen into the API-ILs increased the API’s solubility in water by more than 850 times compared with the original API, and the thermostability was satisfactory with a lower glass transition temperature (tg). Moreover, the variation trends of solubility, hydrophilicity, and Kow were consistent with the different structures of naproxen-based ILs, except for benzalkonium naproxen. The CMC (10–5–10–6 M) in water and ethanol demonstrated that the naproxen-based ILs were surface activite ILs. The IC50 values exhibited the low cytotoxicity of the naproxen-based ILs, which was better than 100 μM. The results provide essential information and a research basis for future topical and transdermal administration and oral administration of naproxen-based ILs.
研究领域:
药学
·
化学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BULLETIN DU CANCER
·
2023
·
IF 1.2
Siyan Zhang,Xingyao Zhang,Dong Zhang,Liang Wei,Bin Xiong,Qi Meng,Shougang Jiang
Summary Introduction Gambogic acid (GA) as an active compound isolated from Gamboge, have been investigated for many years and proved to be a promising natural anticancer agent for clinical treatment . This study aimed to investigate the inhibitory effect of docetaxel (DTX) combined with gambogic acid on bone metastasis of lung cancer. Methods The anti-proliferation effect of the combination of DTX and GA on Lewis lung cancer (LLC) cells was determined by MTT assays . The anticancer effect of the combination of DTX and GA on bone metastasis of lung cancer in vivo was explored. Evaluation of the efficacy of drug therapy was performed by comparing the degree of bone destruction and the pathological section of bone tissue of the treated mice with that of the control mice. Results In vitro cytotoxicity, cell migration, and osteoclast-induced formation assay showed that GA enhanced the therapeutic effect of DTX in Lewis lung cancer cell with a synergistic effect. In an orthotopic mouse model of bone metastasis, the average survival of the DTX + GA combination group (32.61d ± 1.06 d) was significantly increased compared with that of the DTX group (25.75 d ± 0.67 d) or GA group (23.99 d ± 0.58 d), * P < 0.01. Conclusion The combination of DTX and GA has synergistic effect and resulted in more effective inhibition of tumor metastasis , providing a strong preclinical rationale for the clinical development of the DTX + GA combination for treating bone metastasis of lung cancer.
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MEDICINAL CHEMISTRY RESEARCH
·
2021
·Vol. 31
·期 1
·165-176
·
IF 1.965
Zhang Fuli,Lai Qingfu,Lai Weihong,Li Ming,Jin Xiaobao,Ye Lianbao
Phloroglucinol compounds isolated from Dryopteris fragrans (L.) Schott showed a variety of biological activities, such as anticancer and anti-inflammatory. In this study, we have made a number of modifications around the scaffold of phloroglucinol and synthesized phloroglucinol derivatives A1–A9, B1–B9 , and C1–C3 . We synthesized these compounds and investigated their effect on four human cancer cell lines (A-549, MCF-7, Hela, HepG2 cell lines) via MTT assay in vitro. The results revealed that all compounds exhibited certain antiproliferative activities on cancer cell lines and excellent inhibitory effects on MCF-7, in which compound C2 was the best with the IC 50 value of 18.49 μM, exceeding that of 5-fluorouracil. Moreover, the cell apoptosis test showed that compound C2 induced apoptosis in a concentration-dependent manner. Furthermore, the results of molecular docking analysis explained the probable interaction between the active compounds and active sites of target protein 4I22 and 1OG5.
研究领域:
药理学
·
化学
·
肿瘤学
·
分子生物学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）