RSC Advances
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2021
·Vol. 11
·期 53
·33219-33234
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IF 3.361
Zhen Wu,Ruiping Gao,Hong Li,Yongde Wang,Yang Luo,Jiang Zou,Bo Zhao,Shiqi Chen
The combinatorial use of dietary jujube (Ziziphus jujuba) and ginger play a critical role in traditional Chinese medicines, folk medicine and dietary therapy. Joint effects were investigated from the viewpoint of the antioxidant (scavenging DPPH˙) and antitumor activities (against SW620 cells) of jujube polysaccharides and ginger 6-gingerol (G6G) alone and in combination. Jujube polysaccharides were extracted, purified, and characterized, and then their inhibiting and apoptotic effects alone and in combination with G6G were evaluated by the cytological tests, including Cell Counting Kit-8, colony-forming, Annexin V-FITC and propidium iodide, TdT-mediated dUTP nick end labeling (TUNEL) staining, and cell cycle assays. Results showed that the purified polysaccharide fraction (ZJPs-II) with average molecular weight of 115 kDa consisted of arabinose, rhamnose, glucose, xylose, and galactose. ZJPs-II and G6G alone dose-dependently scavenged DPPH˙ and inhibited the proliferation of SW620 cells, while their combination showed synergistic interactions (all combination index < 1). The studies further demonstrated that ZJPs-II and G6G alone reduced the cell colony-formation, induced apoptosis and arrested the cell-cycle at G2/M phase, while their combination achieved better effects and significantly arrested the growth at the G0/G1 phase. Collectively, our findings suggest enhancing the intake of jujube polysaccharides and G6G in a combinatorial approach for maintaining health and preventing cancer.
研究领域:
药理学
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肿瘤学
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营养保健品
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传统中药
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产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2018
·Vol. 23
·期 12
·3082
·
IF 3.098
Wei Liu,Fan Wang,Yongchao Zhu,Xue Li,Xiaojing Liu,Jingjing Pang,Weisan Pan
Targeted drug delivery to colon cancer cells can significantly improve the efficiency of treatment. We firstly synthesized carboxyl-modified mesoporous silica nanoparticles (MSN–COOH) via two-step synthesis, and then developed calcium leucovorin (LV)-loaded carboxyl-modified mesoporous silica nanoparticles based on galactosylated chitosan (GC), which are galectin receptor-mediated materials for colon-specific drug delivery systems. Both unmodified and functionalized nanoparticles were characterized by scanning electron microscopy (SEM), transmission electron microscope (TEM), X-ray diffraction (XRD), Fourier transform infrared (FT-IR), nitrogen sorption, and dynamic light scattering (DLS). Drug release properties and drug loading capacity were determined by ultraviolet spectrophotometry (UV).[email protected]–COOH/GC had a high LV loading and a drug loading of 18.07%. In vitro, its release, mainly by diffusion, was sustained release. Cell experiments showed that in SW620 cells with the galectin receptor, the[email protected]–COOH/GC metabolized into methyl tetrahydrofolic acid (MTHF) and 5-fluorouracil (5-FU)@MSN–NH2/GC metabolized into FdUMP in vivo. MTHF and 5-fluoro-2′-deoxyuridine 5′-monophosphate (FdUMP) had combined inhibition and significantly downregulated the expression of thymidylate synthase (TS). Fluorescence microscopy and flow cytometry experiments show that MSN–COOH/GC has tumor cell targeting, which specifically recognizes and binds to the galectin receptor in tumor cells. The results show that the nano-dosing system based on GC can increase the concentrations of LV and 5-FU tumor cells and enhance their combined effect against colon cancer.Keywords:calcium leucovorin;MSN–COOH;galactosylated chitosan (GC);[email protected]–COOH/GC;galectin receptor;SW620 cells
研究领域:
药学
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纳米技术
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癌症研究
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
Gastroenterology Report
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2020
·Vol. 8
·期 6
·465-475
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IF 2.96
Hou Yong-Qiang,Wang Ying-Ying,Wang Xing-Can,Liu Yao,Zhang Chun-Ze,Chen Zhe-Sheng,Zhang Zhe,Wang Wei,Kong De-Xin
BackgroundColorectal cancer (CRC) is one of the leading causes of cancer death worldwide. Novel drugs for CRC therapy are urgently needed. Digoxin has been in clinical use for treatment of heart failure and atrial arrhythmias for many years. Fragmentary reports suggested that digoxin might have antitumor efficacy on CRC. Here, we aimed to investigate the antitumor effect of digoxin on human CRC cells and the underlying mechanism.MethodsCell viability was determined using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and plate colony formation assay. The effects of digoxin on cell-cycle distribution and apoptosis were analysed by flow cytometry. The anti-metastatic effect on tumor cells was determined by wound-healing assay and transwell assay. Anti-angiogenic effect was examined by determining the inhibition against proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). Mechanism study was performed by Western blot, enzyme-linked immunosorbent assay (ELISA), and gelatin-zymography assay.ResultsDigoxin potently inhibited cell proliferation, induced G1-phase and G2/M-phase arrest in colorectal-cancer HCT8 and SW620 cells, respectively. No obvious apoptosis was observed in the treated cells. Anti-metastatic activities were shown on HCT8 cells by inhibiting the migration and invasion. Meanwhile, the expression of MMP2, MMP9, and phosphorylated Integrinβ1 were decreased. Digoxin inhibited the proliferation, migration, and tube formation of HUVECs and reduced HIF1α expression and vascular endothelial growth factor A (VEGF-A) secretion in HCT8 cells, suggesting anti-angiogenic activity. Furthermore, digoxin significantly reversed ABCB1-mediated multidrug resistance on SW620/Ad300 cells.ConclusionOur findings suggest that digoxin has the potential to be applied as an antitumor drug via inhibiting proliferation and metastasis as well as reversing the ABCB1-mediated multidrug resistance of colorectal cancer.
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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分子生物学
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DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
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2017
·
IF 1.74
Jing Wang,TongMing Li,Linquan Zang,Xuediao Pan,Sujun Wang,Yanyan Wu,Guixiang Wang
Apigenin is a nonmutagenic flavonoid that has antitumor properties. Polyamines are ubiquitous cellular polycations, which play an important role in the proliferation and differentiation of cancer cells. Highly regulated pathways control the biosynthesis and degradation of polyamines. Ornithine decarboxylase (ODC) is the rate-limiting enzyme in the metabolism, and spermidine/spermine-N1-Acetyl transferase (SSAT) is the rate-limiting enzyme in the catabolism of polyamines. In the current study, the effect of increasing concentrations of apigenin on polyamine levels, ODC and SSAT protein expression, mRNA expression, cell proliferation and apoptosis, and the production of reactive oxygen species (ROS) was investigated in SW620 colon cancer cells. The results showed that apigenin significantly reduced cell proliferation, decreased the levels of spermidine and spermine, and increased previously downregulated putrescine contents. Apigenin also enhanced SSAT protein and mRNA levels and the production of reactive oxygen species in SW620 cells, though it had no significant effect on the levels of ODC protein or mRNA. Apigenin appears to decrease the proliferation rate of human SW620 cells by facilitating SSAT expression to induce polyamine catabolism and increasing ROS levels to induce cell apoptosis.
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Bioscience-Landmark
·
2022
·Vol. 27
·期 5
·160
·
IF 3.115
Yuzhu Cao,Keqin Lu,Yawen Xia,Yufei Wang,Aiyun Wang,Yang Zhao
Background: The interactions between platelets and tumor cells are well-known to play important roles in the progression of malignant tumors. Danshensu, a main water-soluble component of Salvia miltiorrhiza, can resist platelet aggregation and exert significant anti-tumor effects on various types of tumors. However, whether Danshensu could inhibit the progression of malignant tumors by suppressing the activities of platelets had not been reported. Methods: The effects of Danshensu on the platelet activity and epithelial-mesenchymal transformation (EMT)-like invasive phenotype of SW620 colon cancer cells were assessed by stimulating with the supernatants from co-cultured platelets and SW620 cells with direct contact (SCP). The expression and secretion of proteins were determined by western blot and enzyme-linked immunosorbent assay (ELISA), respectively. Hematoxylin and eosin (H&E) staining was performed to analyzed the histopathology of tumor tissues and immunohistochemical staining was conducted to examine the protein expression in tumors. Results: Co-incubation of SW620 cells with platelets directly or SCP both generated long spindle-shaped invasive phenotype. Pretreatment of platelets with Danshensu (25 μM) inhibited the morphological changes of SW620 cells induced by SCP, which was associated with the inhibitory effects of Danshensu on platelet secretion. Danshensu diminished the secretion of a list of biological factors in SCP, including interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), IL-1β and vascular endothelial growth factor (VEGF) that are all involved in tumor cell EMT and chemoresistance. Moreover, Danshensu up-regulated the expression of E-cadherin but down-regulated the levels of N-cadherin and Vimentin, resulting in the repression of SW620 cell migration. It was also shown that Danshensu enhanced the sensitivity of SW620 cells to oxaliplatin by suppressing the expression of MDR1. Furthermore, Danshensu could not only reduced the growth of subcutaneous tumors and liver metastasis that induced by SCP, but also down-regulated the expression of MDR1 in vivo. Mechanistic studies revealed that Danshensu suppressed the activation of the TGF-β/Smad signaling pathway. Conclusions: Danshensu attenuated EMT-like characteristics and chemoresistance by inhibiting secretion capability of platelets and activation of the TGF-β/Smad signaling pathway, suggesting that it may be optimized to be a therapeutic agent for fighting against colon cancer.
研究领域:
肿瘤学
·
药理学
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细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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