MOLECULES
·
2023
·Vol. 28
·期 13
·5047
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IF 4.6
Yan Wang,Youbin Li,Dong Liu,Danyang Zheng,Xiaogang Li,Chang Li,Caihui Huang,Yun Wang,Xuesong Wang,Qifu Li,Junyu Xu
Glioblastoma (GBM) is a deadly brain tumor characterized by signaling dysregulation and aberrant cell cycle control. The CDK4/6-Rb axis is dysregulated in approximately 80% of all GBM cases. In this study, the anti-GBM effect of a novel pyrimidin-2-amine, LH20 was evaluated in vitro using the primary GBM cell lines U87MG and U251. GBM cells were administered LH20 at concentrations of 0.1, 1, 4, 8, 10, 20, 100, and 200 µM for 24 and 48 h, and the proliferation rate was evaluated using a CCK8 assay. Migration, apoptosis, and cell cycle were also assessed using a wound healing assay, Annexin V-FITC/PI apoptosis assay, and cell cycle staining, respectively. The targets of LH20 were predicted using SwissTargetPrediction and molecular docking. Western blotting analysis was performed to confirm the anti-GBM mechanism of LH20. We found that at concentrations of 4, 8, and 10 µM, LH20 significantly inhibited the proliferation and migration of U87MG and U251 cells, induced late phase apoptosis, promoted tumor cell necrosis, and arrested the G2/M phase of the cell cycle. LH20 also inhibited CDK4 and CDK6 activities by decreasing the phosphorylation of Rb. Our results suggest LH20 as a potential treatment strategy against GBM.Keywords:LH20;glioblastoma;apoptosis;G2/M;mitochondrial;CDKs
研究领域:
肿瘤学
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分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
SOUTH AFRICAN JOURNAL OF BOTANY
·
2021
·
IF 2.315
Kiren Mustafa,Shaoxuan Yu,Wen Zhang,Hassan Mohamed,Tahira Naz,Haifang Xiao,Yingxin Liu,Yusuf Nazir,Abu Bakr Ahmad Fazili,Shaista Nosheen,Xueyuan Bai,Yuanda Song
Liver cancer is one of the most frequent causes of cancer-related deaths worldwide. The current study sought to screen, for the first time, a Ficus carica variety from the Shandong province of China against hepatocellular (HepG2) cells. Crude extracts of F. carica with various polarities were prepared and screened against HepG2 cells. The acetone extract of the leaf (FLA) exhibited significant antiproliferative effects against HepG2 cells (IC 50 = 0.179 mg/mL) while producing the least toxicity on normal human umbilical vein endothelial cells (HUVECs). Biochemical evidence of apoptosis was confirmed by staining with DAPI and AO/EB. FLA also exhibited moderate anti-colonization potential against the population of HepG2 cells. It selectively arrested the cell cycle of HepG2 cells at the S phase and exerted anticancer activity by significantly increasing the reactive oxygen species (1.59 fold) inside the cells, which subsequently resulted in loss of the mitochondrial membrane potential as revealed by JC-1 probe assay. FLA downregulated the expression of tumor-promoter Transcription Factor (TP53), anti-apoptotic proteins (Bcl-2), and cell cycle regulatory kinases (CDK1, 5, 9) with respect to untreated cells for 24 h, 48 h, and 72 h. High-performance liquid chromatography (HPLC) of FLA revealed the presence of gallic acid and quercetin as major antiproliferative compounds along with trace amounts of rutin, luteolin, apigenin, benzoic acid, and β-sitosterol. Notably, our study showed FLA operating via novel mechanisms involving reactive oxygen species (ROS) generation and CDKs involvement in HepG2 cells. Thus, it suggests that FLA may be a potential source of new drugs in the treatment of liver cancer.
研究领域:
肿瘤学
·
药理学
·
植物学
·
分子生物学
✓ 已验证
DOI
高影响因子
AQUACULTURE
·
2025
·
IF 3.9
Lukuan Li,Zhe Wang,Tong Wang,Nannan Zhou,Fang Qiao,Zhen-Yu Du,Mei-Ling Zhang
Short-chain fatty acids (SCFAs) can enhance the growth of aquatic animals and improve flesh quality through the gut-muscle axis. However, the effects of valeric acid, one of the SCFAs, on aquatic animals remain unreported. This study sought to explore the effects of valeric acid on Nile tilapia ( Oreochromis niloticus ). A total of 360 Juvenile tilapia (mean weight, 1.820 ± 0.007 g) with 3 tanks for each treatment were randomly assigned to 12 rectangular acrylic tanks and fed with four isolipidic (6 % lipid) and isonitrogenous (37 % protein) diets for 60 days, including a control diet (CK) and three experimental diets supplemented with 500 mg/kg (CK + LV), 1000 mg/kg (CK + MV), and 2000 mg/kg (CK + HV) of sodium valerate. The results discovered that the enhanced flesh hardness ( p < 0.01) of tilapia caused by valerate was attributed to decreased myofiber size ( p < 0.001). Transcriptome analysis revealed significant enrichment of the Forkhead box O (FOXO) signaling pathway in the valerate-treated group ( p < 0.001). Subsequent qPCR, western blot, immunohistochemistry, and immunofluorescence analyses demonstrated that valerate inhibited muscle cell proliferation by activating the FOXO signaling pathway, suppressing FOXO nuclear export, and consequently downregulating cyclins and cyclin-dependent kinases (CDKs) ( p < 0.01). Furthermore, valerate suppressed muscle differentiation by inhibiting the transcription and protein levels expression of myogenic regulatory factors (MRFs) ( p < 0.001). Additional validation in C2C12 myoblasts and myotubes confirmed that valerate indeed inhibited myoblasts proliferation and myotubes differentiation ( p < 0.001). These findings indicated that valerate reduced myofiber size by suppressing myoblasts proliferation and myotubes differentiation. This study elucidated the effects and mechanisms of valerate on skeletal muscle and introduced a novel approach to enhance fish flesh hardness.
研究领域:
水产养殖
·
营养学
·
分子生物学
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动物生理学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）