ONCOLOGY REPORTS
·
2017
·Vol. 38
·期 6
·3583-3591
·
IF 2.662
Shilei Zang,Qiling Tang,Fangrui Dong,Huan Liu,Lili Li,Fang Guo,Xuediao Pan,Haorong Lin,Weibin Zeng,Zhaoxu Cai,Qibin Zhong,Ning Zang,Linquan Zang
Curcumol, a polyphenol compound derived from the rhizome of Curcuma, has been established as an antitumor compound against multiple types of cancer, including gastric (GC), lung, liver and breast cancer. However, the molecular mechanisms undelying its anticancer activity in GC are still unclear. In this study, the antitumor efficacy of curcumol was ascertained in human gastric adenocarcinoma MGC-803 cells. An MTT assay was used to assess the viability of the MGC-803 cells treated by curcumol. The results of the Annexin V/propidium iodide (PI) staining followed by fluorescence activated cell sorting (FACS) analysis demonstrated that the cell cycle was arrested in the G2/M phase by curcumol. Annexin V-FITC/PI double staining followed by FACS analysis revealed that curcumol induced apoptosis of MGC-803 cells. FACS analysis after the cells were loaded with a DFCH-DA probe revealed that the level of reactive oxygen species (ROS) increased after the cells were treated with curcumol. In adittion, FACS analysis after the cells were loaded with JC-1 revealed that the level of mitochondrial membrane potential (MMP) decreased after the cells were treated with curcumol. Furthermore, the downregulation of isocitrate dehydrogenase 1 (IDH1) was observed in the MGC-803 cells after being treated with curcumol as determined by western blotting and RT-qPCR. In conclusion, we elucidated the antitumor effect of curcumol on MGC-803 cells and the involved mechanisms related to the induction of apoptosis, the increase of ROS, the decrease of MMP and the downregulation of IDH1.
研究领域:
肿瘤学
·
细胞生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Analytical Methods
·
2019
·Vol. 11
·期 11
·1516-1521
·
IF 2.378
Fujuan Luan,Zuhong Yu,Ling Yin,Xia Leng,Yuxue Shi,Jie Wang,Haibin Shi,Weichang Chen
Matrix metalloproteinase-2 (MMP-2) plays an important role in tumorigenesis and metastasis of gastric cancer. Therefore, specific and sensitive detection of MMP-2 is of great significance for clinical diagnosis and therapeutic evaluation of gastric cancer. Herein, we developed a new approach for accurate detection of MMP-2 activity both in gastric cancer cells and clinical tissues using a fluorescent probe Dab-PLGVRGY-FITC. The capability of the probe for detecting MMP-2 was systematically evaluated in gastric cancer MGC-803 cells and clinical gastric cancer tissues. Around 40-fold fluorescence enhancement at a wavelength of 520 nm was determined for the assays of the probe with recombinant MMP-2. The detection limit of MMP-2 was as low as 42 ng mL−1. Strong fluorescence signals were detected in MGC-803 cells and mouse gastric cancer tissues. Fluorescence signal enhancements of 11 clinical gastric cancer tissue lysates were 5.8 ∼ 9 times (7.53 ± 0.77 on average) higher than those from gastritis patients. This probe could be potentially used for early diagnosis of gastric cancer in clinics.
研究领域:
肿瘤学
·
生物医学工程
·
临床诊断
✓ 已验证
产品关联
DOI
高影响因子
MOLECULES
·
2019
·Vol. 24
·期 21
·3851
·
IF 3.06
Yandong Zhang,Chao Xin,Junqiang Qiu,Zhenyu Wang
Pinecone is a traditional folk herb, which has been used in China for many years. In this paper, the essential oil fromPinus koraiensispinecones (PEO) was obtained by hydrodistillation and 41 compounds were identified by gas chromatography–mass spectrometry (GC-MS), mainly including α-Pinene (40.91%), Limonene (24.82%), and β-Pinene (7.04%). The purpose of this study was to investigate the anti-tumor activity of PEO on MGC-803 cells and its mechanism. Anti-tumor experiments in vitro showed PEO could significantly inhibit the proliferation and migration of MGC-803 cells, and it also could arrest the cell cycle in the G2/M phase, decrease the mitochondrial membrane potential, and induce apoptosis. Finally, the effects of PEO on genes expression on MGC-803 cells were analyzed by RNA sequencing, and results showed that after treatment with PEO, 100 genes were up-regulated, and 57 genes were down-regulated. According to the KEGG pathway and GSEA, FAT4, STK3, LATS2, YAP1, and AJUBA were down-regulated, which were related to HIPPO signaling pathway. Real-time PCR and western blot further confirmed the results of RNA sequencing. These results indicated that PEO may exert anti-tumor activity via the HIPPO/YAP signaling pathway. The anti-tumor mechanism of this oil can be further studied, which is important for the development of anti-tumor drugs.Keywords:pinecone;essential oil;gastric cancer;RNA sequencing;HIPPO/YAP signaling pathway
研究领域:
药理学
·
肿瘤学
·
分子生物学
·
植物科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2022
·Vol. 27
·期 15
·4996
·
IF 4.927
Guang-Xi Yu,Ying Hu,Wei-Xin Zhang,Xin-Yi Tian,Sai-Yang Zhang,Yan Zhang,Shuo Yuan,Jian Song
[1,2,4]Triazolo[1,5-a]pyrimidine and indole skeletons are widely used to design anticancer agents. Therefore, in this work, a series of [1,2,4]triazolo[1,5-a]pyrimidine indole derivatives were designed and synthesized by the molecular hybridization strategy. The antiproliferative activities of the target compoundsH1–H18against three human cancer cell lines, MGC-803, HCT-116 and MCF-7, were tested. Among them, compoundH12exhibited the most active antiproliferative activities against MGC-803, HCT-116 and MCF-7 cells, with IC50values of 9.47, 9.58 and 13.1 μM, respectively, which were more potent than that of the positive drug5-Fu. In addition, compoundH12could dose-dependently inhibit the growth and colony formation of MGC-803 cells. CompoundH12exhibited significant inhibitory effects on the ERK signaling pathway, resulting in the decreased phosphorylation levels of ERK1/2, c-Raf, MEK1/2 and AKT. Furthermore, compound12induced cell apoptosis and G2/M phase arrest, and regulated cell cycle-related and apoptosis-related proteins in MGC-803 cells. Taken together, we report here that [1,2,4]triazolo[1,5-a]pyrimidine indole derivatives, used as anticancer agents via the suppression of ERK signaling pathway and the most active compound,H12, might be a valuable hit compound for the development of anticancer agents.Keywords:[1,2,4]triazolo[1,5-a]pyrimidine;indole;antiproliferative activities;ERK signaling pathway
研究领域:
药物化学
·
肿瘤学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
STEROIDS
·
2014
·
IF 2.716
Bin Yu,Ping-Ping Qi,Xiao-Jing Shi,Li-Hong Shan,De-Quan Yu,Hong-Min Liu
A series of novel steroidal pyran–oxindole hybrids were efficiently synthesized in a single operation through the vinylogous aldol reaction of vinyl malononitrile 3 with substituted isatins involving the construction of C–C and C–O bonds. Some compounds displayed moderate to good cytotoxicity against T24, SMMC-7721, MCF-7 and MGC-803 cells. Compounds 4f and 4i were more potent than 5-Fu against T24 and MGC-803 cells with the IC 50 values of 4.43 and 8.45 μM, respectively. Further mechanism studies indicated that compound 4i induced G2/M arrest and early apoptosis in a concentration- and time-dependent manner.
研究领域:
药物化学
·
肿瘤学
·
合成化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2017
·
IF 2.759
Yanyan Zhu,Yameng Jiang,Lei Shi,Linying Du,Xiaodong Xu,Enxia Wang,Yong Sun,Xin Guo,Boyang Zou,Huaxin Wang,Changyuan Wang,Lidan Sun,Yuhong Zhen
7- O -Geranylquercetin (GQ) is a novel O -alkylated derivate of quercetin . In this study, we evaluated its apoptosis induction effects in human gastric cancer cell lines SGC-7901 and MGC-803 and explored the potential molecular mechanisms. The results demonstrated that GQ lowered viability of SGC-7901 and MGC-803 cells in a dose- and time-dependent manner without apparent cytotoxicity to human gastric epithelial cell line GES-1. GQ could induce apoptosis in SGC-7901 and MGC-803cells, and arrest the gastric cancer cells at G2/M phase. Mechanism study showed that GQ triggered generation of reactive oxygen species (ROS), then activated p38 and JNK signaling pathways , subsequently led to mitochondrial impairment by regulating the expression of Bcl-2, Bcl-xl and Bax, and finally promoted the release of cytochrome c and the activation of caspases to induce apoptosis. In addition, Z-VAD-FMK (caspase inhibitor) could reverse GQ-induced apoptosis. SB203580 (p38 inhibitor) and SP600125 (JNK inhibitor) could rescue GQ-induced cell death and attenuate mitochondrial signal pathway activation. Furthermore, NAC (ROS inhibitor) could rescue GQ-induced cell death, reduce ROS generation, decrease the phosphorylation of p38 and JNK, and then attenuate the activation of mitochondrial signal pathway. Taken together, GQ induces caspase-dependent apoptosis in gastric cancer cells through activating ROS-MAPK mediated mitochondrial signal pathway. This study highlights the potential use of GQ as a gastric cancer therapeutic agent.
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
RSC Advances
·
2018
·Vol. 8
·期 54
·31201-31212
·
IF 2.936
Xiaokang Long,Yao-Fu Zeng,Yunmei Liu,Ying Liu,Tangluo Li,Lanqing Liao,Yu Guo
Genistein amino acid derivatives 4a–4d were synthesized and evaluated for their cytotoxic activities against MCF-7, Hela, MGC-803 and HCT-116 cell lines by MTT assays in vitro. The results revealed that compounds 4a–4d showed better activity than the parent compound genistein. Particularly, compound 4b displayed the most significant anticancer activity against MGC-803 with an IC50 value of 12.08 μM. In addition, the mechanisms of interaction between genistein, compounds 4a–4d and BSA were investigated via multi-spectroscopic techniques such as ultraviolet (UV) spectroscopy, fluorescence, circular dichroism (CD), and molecular docking under physiological conditions. The results suggested that endogenous fluorescence of BSA could be quenched by genistein and compounds 4a–4d via forming BSA-compound complex, which meant a static quenching mechanism was involved. The negative values of enthalpy (ΔH) and entropy (ΔS) indicated that interactions between BSA and the ligands were spontaneous, and hydrogen bonding and van der Waals interactions were involved in the BSA-compound complexion formation. The UV, synchronous and 3D fluorescence results revealed that the micro-environment of tryptophan and conformation of BSA were changed after binding to ligands. CD analysis demonstrated the variation in the secondary structure and that the α-helix content of BSA decreased. Eventually, molecular docking was executed to forecast the binding forces and binding sites between BSA and compounds 4a–4d.
研究领域:
药理学
·
生物化学
·
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）