CHEMICAL RESEARCH IN CHINESE UNIVERSITIES
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2017
·Vol. 33
·期 4
·581-586
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IF 1.024
Guo Jinhua,Tan Bei,Ye Qingmei,Liang Guangping,Yi Min,Jiang Renwang
Two series of novel spin-labeled derivatives of Cinobufagin(compounds 5 and 8 a― 8 f in series 1 with five-membered ring nitroxyl free radical and compounds 6 and 9 a― 9 f in series 2 with six-membered ring nitroxyl free radical) were synthesized. The cytotoxic activities in vitro against two tumor cell lines(HepG2 and HeLa) were evaluated, and the results indicate that all compounds display potent cytotoxicity against HepG2 and HeLa cells, and most compounds show better activities on HeLa cells than on HepG2 cells except for compounds 8 a and 9 d. Generally, the compounds in series 2 have more potent cytotoxic activity against HepG2 than the compounds in series 1. Especially, compounds 6 and 9 f in series 2 exhibit even more potent activities against the two tumor cell lines than Cinobufagin. Thus incorporation of different L -amino acids as the linker changed the cytotoxic profile of the spin-labeled Cinobufagin. In addition, the representative compound 9 f significantly changed the cell cycle distribution and led to HeLa cell cycle arrested at G 2 /M phase.
研究领域:
药物化学
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肿瘤学
·
分子生物学
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药理学
·
有机合成
✓ 已验证
DOI
高影响因子
Nano Research
·
2021
·Vol. 14
·期 11
·3988-3998
·
IF 8.897
He Jiaqi,Chen Guoqin,Zhao Peng,Ou Caiwen
Bufalin is efficacious in treating various tumors, however, the clinical application of which is restricted by the myocardial toxicity. Developing a smart synergetic delivery system is widely considered as a promising therapeutic strategy. To address this issue, a black phosphorus hybrid polypeptides hydrogel was designed to highly load bufalin, and achieved near-infrared (NIR)-controllable drug release with synergistic photothermal-chemo therapeutic effect. Black phosphorus nanosheets (BPNSs) and bufalin were co-loaded in temperature-sensitive supramolecular hydrogel to receive smart hybridization (BP-bufalin@SH). With NIR irradiation (1 W·cm −2 ), BP-bufalin@SH exhibited a rapid and large temperature increase and released bufalin via light-controllable manner, with which the side effects of bufalin were greatly decreased. Combined with photothermal-chemo therapeutic effect, BP-bufalin@SH could collapse the mitochondrial transmembrane potential resulting in the irreversible apoptosis of tumor cells, and realize a highly efficient in vivo tumor elimination with good biosafety and biocompatibility. This work provides a new hydrogel platform for controlling bufalin release, and thus further promotes the practical application on antitumor therapy.
研究领域:
药学
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纳米技术
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癌症治疗
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2020
·
IF 3.69
Li-Juan Zhao,Hai-Yu Zhao,Xiao-Lu Wei,Fei-Fei Guo,Jun-Ying Wei,Hong-Jie Wang,Jian Yang,Zhi-Gang Yang,Nan Si,Bao-Lin Bian
Ethnopharmacological relevance Arenobufagin (ArBu) is an important anti-tumor ingredient of Chan'su which has long been used as traditional Chinese medicine in clinic for tumor therapy in China. Aim of the study The purpose of our study is to investigate the lipid homeostasis regulation effects of ArBu on zebrafish model of liver cancer and hepatoma cells, and to provide a reference for further clarifying its active mechanisms. Materials and methods The zebrafish xenograft model was established by injecting HepG2 cells stained with CM-Dil red fluorescent dye . Both the xenograft model and HepG2 cells were used to evaluate the anti-hepatoma activity of ArBu. High performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was the main method to study lipidomics, proteomics and the semiquantification of endogenous metabolites. Bioinformatics was used as an assistant tool to further explore the antitumor mechanism of ArBu. Results The lipidomics analysis revealed that ArBu caused differential lipids changes in a dose-dependent manner, including PCs, PEs, TGs, SMs, DGs, Cer and PA . PCs, PEs, SMs and TGs were markedly altered in both two models. The influence of glycerophospholipid metabolism was the major and commonly affected pathway. Notably, DGs and Cer were significantly changed only in HepG2 cells. Furthermore, the proteomics research in HepG2 cells fished the target proteins related to lipid homeostasis abnormalities and tumor suppression. ArBu reduced the expression of 65 differential proteins associated with the lipid metabolism, apoptosis and autophagy, such as LCLAT1, STAT3, TSPO and RPS27. Meanwhile, 7 amino acids of 29 determined metabolites were significantly changed, including tyrosine, glutamate , glutamine, leucine , threonine , arginine and isoleucine . Conclusion ArBu has a significant anti-hepatoma effect in vitro and a therapeutic effect on zebrafish xenograft model. It regulated the lipid homeostasis. Activated SM synthase and arginine deiminase , inhibited sphingomyelinase , amino acid supply and JAK-STAT3 signaling pathway, and the affected glycerophospholipid metabolism might explain these results.
研究领域:
药理学
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肿瘤学
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生物化学
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分子生物学
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民族药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG RESISTANCE UPDATES
·
2023
·
IF 24.3
Wei Zhang,Yibao Fan,Jinze Zhang,Dan Shi,Jiahui Yuan,Milad Ashrafizadeh,Wei Li,Man Hu,A.M. Abd El-Aty,Ahmet Hacimuftuoglu,Michael Linnebacher,Yongxian Cheng,Weiguang Li,Shuo Fang,Peng Gong,Xianbin Zhang
Aims Multidrug resistance in pancreatic cancer poses a significant challenge in clinical treatment. Bufalin (BA), a compound found in secretions from the glands of toads, may help overcome this problem. However, severe cardiotoxicity thus far has hindered its clinical application. Hence, the present study aimed to develop a cell membrane-camouflaged and BA-loaded polylactic-co-glycolic acid nanoparticle (CBAP) and assess its potential to counter chemoresistance in pancreatic cancer. Methods The toxicity of CBAP was evaluated by electrocardiogram, body weight, distress score, and nesting behavior of mice. In addition, the anticarcinoma activity and underlying mechanism were investigated both in vitro and in vivo . Results CBAP significantly mitigated BA-mediated acute cardiotoxicity and enhanced the sensitivity of pancreatic cancer to several clinical drugs, such as gemcitabine, 5-fluorouracil, and FOLFIRINOX . Mechanistically, CBAP directly bound to nucleotide-binding and oligomerization domain containing protein 2 (NOD2) and inhibited the expression of nuclear factor kappa-light-chain-enhancer of activated B cells. This inhibits the expression of ATP-binding cassette transporters, which are responsible for chemoresistance in cancer cells. Conclusions Our findings indicate that CBAP directly inhibits NOD2. Combining CBAP with standard-of-care chemotherapeutics represents a safe and efficient strategy for the treatment of pancreatic cancer.
研究领域:
肿瘤学
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药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Yichen Liu,Dahai Hou,Hui Wang,Qiuying Yan,Yunzhu Xu,Qibiao Wu,Dan Dong,Weixing Shen,Weiwei Tao,Haibo Cheng,Dongdong Sun
Colorectal cancer, a highly invasive malignancy, poses significant treatment challenges due to the immunosuppressive tumor microenvironment. Tumor-associated macrophages, which primarily exhibit the M2 phenotype, play a key role in cancer progression and immune evasion. Reprogramming these M2 macrophages to the tumor-suppressive M1 phenotype represents a promising therapeutic approach to enhance antitumor immunity. In this study, we developed a calcium lactate nanoparticle-based delivery system (CLBRP) to codeliver bufalin, a potent Na + /K + -ATPase inhibitor with anticancer properties, and CRISPR-Cas9, which targets the immune checkpoint CD47. The system releases its payload under low pH conditions typical of the tumor microenvironment, increasing extracellular Ca 2+ and intracellular osmotic pressure, thereby inducing pyroptosis and immunogenic cell death. Bufalin induces cancer cell apoptosis, inhibits Na + /K + -ATPase, and triggers pyroptosis, which activates a strong immune response. Additionally, bufalin and D-lactic acid synergistically promote macrophage repolarization to the M1 phenotype. CRISPR-Cas9-mediated editing of the CD47 gene on tumor cells blocks antiphagocytic signals, enhancing M1 macrophage phagocytosis and increasing the antitumor immune response. This multimodal strategy triggers strong local antitumor effects and controls metastatic lesions via systemic immune activation, demonstrating significant potential for colorectal cancer treatment. Furthermore, this approach offers a new direction for overcoming resistance to immunotherapies and improving clinical outcomes.
研究领域:
肿瘤学
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免疫治疗
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纳米医学
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基因编辑
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癌症生物学
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肿瘤微环境
✓ 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）