RSC Advances
·
2019
·Vol. 9
·期 51
·29711-29720
·
IF 3.049
Yan Zhang,Yunyun Wang,Yuxun Zhao,Wen Gu,Yongqiang Zhu,Shifa Wang
A series of novel camphor-based pyrimidine derivatives (3a–3x) have been synthesized; their structures were determined by using conventional methods and compound 3f was further confirmed through single crystal XRD analysis. The cytotoxic activity of the target compounds against a panel of human normal (GES-1) and cancer cell lines (MDA-MB-231, RPMI-8226, A549) was evaluated by MTS assay. Here we found that compound 3f exhibited the strongest anti-tumor activity, comparable to that of etoposide, and had much lower cytotoxicity to normal GES-1 cells (IC50 > 50 μM) than the reference drug (IC50 = 8.89 μM). Subsequent mechanism studies in MDA-MB-231 cells revealed that compound 3f caused G0/G1 phase arrest and apoptosis in a dose dependent manner. Moreover, the loss of mitochondrial membrane potential and enhancement of cellular ROS levels were also observed upon 3f treatment, which indicated that 3f exerted cytotoxic activity by a ROS-mediated mitochondrial apoptosis pathway. This result was confirmed by a significant increase in the expression of pro-apoptotic proteins Bax, cytochrome C and caspase-3, and downregulation of anti-apoptosis protein Bcl-2. Overall, 3f can be adopted for further investigation in the development of antitumor agents based on natural products.
研究领域:
肿瘤学
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药理学
·
细胞生物学
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DOI
PubMed
高影响因子
Frontiers in Cell and Developmental Biology
·
2020
·
IF 5.186
Hong Lin,Chen Jundixia,Wu Fang,Wu Fengjiao,Shen Xin,Zheng Peisen,Shao Rongrong,Lu Kongqin,Liu Zhiguo,Chen Daoxing,Liang Guang,Cai Yuepiao,Zou Peng,Xia Yiqun
Colon cancer is one of the leading causes of cancer-related death in the world. The development of new drugs and therapeutic strategies for patients with colon cancer are urgently needed. Isodeoxyelephantopin (ESI), a sesquiterpene lactone isolated from the medicinal plant Elephantopus scaber L., has been reported to exert antitumor effects on several cancer cells. However, the molecular mechanisms underlying the action of ESI is still elusive. In the present study, we found that ESI potently suppressed cell proliferation in human colon cancer cells. Furthermore, our results showed that ESI treatment markedly increased cellular reactive oxygen species (ROS) levels by inhibiting thioredoxin reductase 1 (TrxR1) activity, which leads to activation of the JNK signaling pathway and eventually cell death in HCT116 and RKO cells. Importantly, we found that ESI markedly enhanced cisplatin-induced cytotoxicity in HCT116 and RKO cells. Combination of ESI and cisplatin significantly increased the production of ROS, resulting in activation of the JNK signaling pathway in HCT116 and RKO cells. In vivo, we found that ESI combined with cisplatin significantly suppressed tumor growth in HCT116 xenograft models. Together, our study provide a preclinical proof-of-concept for ESI as a potential strategy for colon cancer treatment.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED POLYMER SCIENCE
·
2021
·Vol. 138
·期 48
·51537
·
IF 3.125
Haoying Song,Na Hu,Ziwei Gao,Baohui Zhang,Junjie Hu,Zhenpeng Qiu,Guohua Zheng,Cong Chang,Yan Meng
Gold nanoparticles (AuNPs) with size of 12 ~ 25 nm were loaded on the dendritic nanotubes (DNTs), which were self-assembled by the triple-helix polysaccharides from black fungus (AF1). The characterization results proved that the AuNPs were dispersed on the surface of DNTs without affecting their tubular structure. Due to the dendritic structure, the loading content of AuNPs could arrived at 46.4%. Moreover, the potential anticancer activities of the complex (DNT-Au) were evaluated by the induction of apoptosis in HepG2 cells. It was found DNT-Au could be taken up by cells and enter into lysosomes, further inducing apoptosis in HepG2 cells by ROS-mediated mitochondrial dysfunction. This work was benefit for the development of natural polysaccharide as a substrate to stabilize nanoparticles in biomedical fields.
研究领域:
纳米技术
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癌症生物学
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生物医学工程
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药学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2018
·
IF 7.877
Xiaopeng Mo,Zening Zheng,Yang He,Huihai Zhong,Xuejia Kang,Mingjie Shi,Tuanbing Liu,Zheng Jiao,Yongzhuo Huang
Effective treatment of malignant glioma still remains a formidable challenge due to lack of the effective BBB-permeable drugs and efficient brain delivery methods, and the pharmacotherapy options are very limited. Therefore, to develop an effective therapeutic strategy is a pressing need. In this work, a noncytotoxic drug combination (i.e., simvastatin and fenretinide) was revealed to be potent for treating glioma, which was co-encapsulated into a TPGS-TAT-embedded lactoferrin nanoparticle system for achieving brain-targeted biomimetic delivery via the LRP-1 receptor. It was shown that the lactoferrin nanoparticle repolarized the tumor-associated macrophages from the M2 phenotype to M1 via regulating the STAT6 pathway, as well as induced the ROS-mediated mitochondrial apoptosis by inhibiting the Ras/Raf/p-Erk pathway in the glioma cells. The antiglioma efficacy was further demonstrated in both the subcutaneous and orthotopic glioma models. The repolarization of tumor-associated macrophages not only prompted the ROS generation but also induced the innate immunity (e.g., antitumor cytokine release). This delivery and therapeutic strategy provides a novel modality for the glioma treatment.
研究领域:
神经肿瘤学
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药理学
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纳米医学
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癌症生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2019
·Vol. 8
·期 23
·1900911
·
IF 6.27
Peng Ji,Haiqin Huang,Shirui Yuan,Le Wang,Siqi Wang,Yiwei Chen,Na Feng,Hanitrarimalala Veroniaina,Ziheng Wu,Zhenghong Wu,Xiaole Qi
Reactive oxygen species (ROS)-mediated apoptosis is considered a crucial therapeutic mechanisms for artesunate (AS). As an Fe(II)-dependent drug, the anticancer effect of AS is often limited due to insufficient Fe(II) concentration in targeted cells. To overcome this problem, a recombinant apoferritin nanocarrier containing ferriferous oxide (M-HFn) is constructed to produce auxiliary exogenous Fe(II) when delivering AS to cancer cells. Here, the newly fabricated AS-loaded M-HFn nanoparticles (M-HFn@AS NPs) can significantly improve the tumor-specific targeting and intracellular uptake efficiency of AS in human cervical carcinoma cells. After being captured in the acidic cavity of endosomes, M-HFn@AS NPs can simultaneously release Fe(II) and allow AS to activate satisfactory ROS-mediated apoptosis. Furthermore, in vivo studies demonstrate that M-HFn@AS NPs can selectively accumulate in tumors to efficiently inhibit tumor growth. Thus, M-HFn@AS NPs are a promising system to enhance the therapeutic effect of Fe(II)-dependent drugs.
研究领域:
药学
·
癌症研究
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纳米技术
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2023
·
IF 14
Zhenzhen Feng,Gui Chen,Min Zhong,Ling Lin,Ziyi Mai,Yan Tang,Guimei Chen,Wen Ma,Guang Li,Yuanyuan Yang,Zhiqiang Yu,Meng Yu
Pyroptosis is an inflammatory form of programmed cell death (PCD) that is regulated by the Gasdermin protein family in response to various stimuli, playing a critical role in the development of tumor therapy strategies. However, cancers are generally known to escape from PCD via immunosuppressive pathways or other resistant mechanisms. In this study, an acid-responsive Fe/Mn bimetal-organic framework nanosystem carrying metal ions and immune adjuvant R848 (FeMn@R@H) was designed for combining pyroptosis and augmented immunotherapy. The FeMn@R@H would be triggered to disintegrate and release Fe 3+ and Mn 2+ ions in response to the acidic tumor microenvironment (TME), thereby initiating Fenton-like reactions for ROS-mediated pyroptosis. On the one hand, the pyroptosis-caused cell rupture would induce the release of proinflammatory cytokines and immunogenic constituents from tumor cells, further resulting in immunogenic cell death (ICD) to promote antitumor immune responses. On the other hand, the co-delivered R848 could reverse suppressive tumor immune microenvironment (TIME) and induce inflammatory responses by activating the TLR7/8 pathway. In conclusion, this tumor-specific therapy system can co-deliver metal ions and R848 to tumor tissues to perform pyroptosis-mediated PCD and augmented anti-tumor immunotherapy.
研究领域:
癌症生物学
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纳米技术
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免疫治疗
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药学
✓ 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）