MOLECULES
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2023
·Vol. 28
·期 16
·6014
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IF 4.6
Shanbin Chen,Dong Zhao,Chunguang Luan,Jia Zheng,Wei Liu,Zheng Feng,Ruiqi Luo,Xinglin Han,Deliang Wang
Ferulic acid (FA) is a bioactive compound found in traditional Chinese herbal medicine; for example, it is present in Xinjiang Ferula, but also in strong-flavor Chinese baijiu. FA has been shown to play a crucial role in treating oxidative stress, skin whitening, and eye diseases. In this study, the potential role of FA as a means of inducing apoptosis and inhibiting colon cancer induced by the transplantation of CT26 cells was investigated. The results show that FA adjuvant treatment caused an upregulation in the expression of genes related to autophagy while simultaneously suppressing the expression of inflammatory response elements and improving the bodyweight, glutamic pyruvic transaminase (ALT), and glutamic oxaloacetic transaminase (AST) in vivo. Furthermore, FA inhibited the proliferation of CT26 cells and induced apoptosis, specifically by activating the phosphorylation of ERK and JNK to enhance the essential proteins BCL-2 and BAX in the apoptosis pathway. These results suggest that FA could be a promising auxiliary therapeutic agent for the treatment of colon cancer. Further research is needed to better understand the mechanisms underlying the beneficial effects of FA and its synergistic effects with other compounds.Keywords:ferulic acid;apoptosis;autophagy;MAPK pathway
研究领域:
药理学
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肿瘤学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
XENOBIOTICA
·
2023
·
IF 1.8
Chunhong Wu,Yifei Xiao,Caimei Wu,Dihao Xie,Meixue Luo,Dingyi Yao,Min Chen,Danyi Lu
BCRP (breast cancer resistance protein) is a crucial efflux transporter involved in the regulation of the pharmacokinetics and pharmacodynamics of a wide range of drugs. Herein, we aimed to investigate a potential role for the nuclear receptor REV-ERBα in the regulation of BCRP expression and sulfasalazine (a BCRP probe substrate) pharmacokinetics.Regulation of BCRP expression by REV-ERBα was assessed using Rev-erbα-/- mice and AML12 and CT26 cells. Pharmacokinetic analysis was performed with Rev-erbα-/- and wild-type mice after sulfasalazine administration.We found that the expression levels of BCRP mRNA and protein were downregulated in the liver and small intestine of Rev-erbα-dificient mice. In line with this, Rev-erbα ablation increased the systemic exposures of oral sulfasalazine.Positive regulation of BCRP expression and function by REV-ERBα was furtherly confirmed in AML12 and CT26 cells. Moreover, indirect regulation of Bcrp expression by REV-ERBα was potentially mediated by a negative transcription factor DEC2, which is a downstream target of REV-ERBα.In conclusion, REV-ERBα positively regulates BCRP expression in mice, thereby affecting sulfasalazine pharmacokinetics.
研究领域:
药理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
NANOTECHNOLOGY
·
2020
·Vol. 31
·期 25
·255101
·
IF 3.551
Yi Zhang,Shuxin Jia,Jintao Yuan,Peide Zhu,Ying Gan,Guangfang Fan,Shuling Yu,Jiahua Shi
Drug delivery carriers hold tremendous promise for improving cancer treatment, and polyrotaxane (PR) has shown excellent drug-carrying properties. However, there have been some reports that, when used as a drug carrier, water-soluble PR is not easily labeled with organic fluorescent dyes. Herein, we synthesized a drug-loaded fluorescent porphyrin-terminated PR (PR-COOH) which can be used as a tracer material in drug and gene delivery. The structure, morphology and zeta potential of PR-COOH were characterized by nuclear magnetic resonance, high-resolution transmission electron microscopy and zeta potentiometry. In this research, cisplatin (CDDP) is used as a model drug. The zeta potential, drug encapsulation efficiency and drug release of CDDP-loaded PR (PR-COOH-Pt) were studied. Confocal laser scanning microscopy showed that PR-COOH could be internalized by HeLa and CT26 cells. The antitumor efficacy of PR-COOH-Pt was investigated in vitro by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and in vivo by a xenograft tumor model. The results showed that PR-COOH-Pt could significantly inhibit tumor growth; thus PR-COOH-Pt has a promising role in cancer therapy.
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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生物医学工程
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产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
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2024
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IF 5.3
Siyu Li,Zhaorong Ouyang,Mengjie Zhang,Shuai Guo,Biao Cai,Houli Liu
Selenomethionine (SeM) holds great potential applications in tumor therapy. However, the tumor-targeting ability of SeM in vivo remains challenging. Herein, we utilize extracellular vesicles (EV) as tumor-targeted drug delivery systems to achieve enhanced specific targeting and antitumor efficacy. The carboxyl groups of SeM are conjugated with the amino groups of EV derived from low-pH culture medium reprogrammed CT26 cells (LEV) to obtain the SeM-based formulations (SMLEV), which can actively target tumor cells and enhance uptake efficacy through specific behaviors of LEV to their parent cells. Mechanistic studies indicate that SMLEV can induce reactive oxygen species (ROS) overproduction, mitochondrial dysfunction, as well as Caspase-9 and Caspase-3 activation. Here, SMLEV exhibit enhanced cytotoxic potential toward colon tumor (CT26) cells. After systemic administration, the growth of tumors is inhibited in vivo using CT26 tumor-bearing mice. Our findings can provide insights and a strategy in developing SeM delivery for tumor treatment.
研究领域:
肿瘤学
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药学
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生物技术
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产品关联
DOI
高影响因子
Acta Biomaterialia
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2023
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IF 9.7
Yuan-Fu Ding,Xun Xu,Junyan Li,Ziyi Wang,Jingwei Luo,Greta S.P. Mok,Shengke Li,Ruibing Wang
Dual- or multi-modality combination therapy has become one of the most effective strategies to overcome drug resistance in cancer therapy, and the optimized ratio of the therapeutic agents working on the tumor greatly affects the therapeutic outcomes. However, the absence of a facile method to optimize the ratio of therapeutic agents in nanomedicine has, at least in part, impaired the clinical potential of combination therapy. Herein, a new cucurbit[7]uril (CB[7])-conjugated hyaluronic acid (HA) based nanomedicine was developed, in which both chlorin e6 (Ce6) and oxaliplatin (OX) were co-loaded non-covalently at an optimized ratio via facile host-guest complexation, for optimal, combined photodynamic therapy (PDT)/chemotherapy. To maximize the therapeutic efficacy, a mitochondrial respiration inhibitor, atovaquone (Ato), was also loaded into the nanomedicine to limit consumption of oxygen by the solid tumor, sparing oxygen for more efficient PDT. Additionally, HA on the surface of nanomedicine allowed targeted delivery to cancer cells with over-expressed CD44 receptors (such as CT26 cell lines). Thus, this supramolecular nanomedicine platform with an optimal ratio of photosensitizer and chemotherapeutic agent not only provides an important new tool for enhanced PDT/chemotherapy of solid tumors, but also offers a CB[7]-based host-guest complexation strategy to facilely optimize the ratio of therapeutic agents for multi-modality nanomedicine. Statement of significance Chemotherapy remains the most common modality for cancer treatment in clinical practice. Combination therapy by co-delivery of two or more therapeutic agents has been recognized as one of the most effective strategies to improve therapeutic outcome of cancer treatment. However, the ratio of loaded drugs could not be facilely optimized, which may greatly affect the combination efficiency and overall therapeutic outcome. Herein, we developed a hyaluronic acid based supramolecular nanomedicine with facile method to optimize the ratio of two therapeutic agents for improved therapeutic outcome. This supramolecular nanomedicine not only provides an important new tool for enhanced photodynamic therapy/chemotherapy of solid tumors, but also offers insights in using macrocyclic molecule-based host-guest complexation to facilely optimize the ratio of therapeutic agents in multi-modality nanomedicine.
研究领域:
纳米技术
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药学
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肿瘤学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Journal of Pharmaceutical Analysis
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2022
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IF 14.026
Min Mu,Xiaoyan Liang,Na Zhao,Di Chuan,Bo Chen,Shasha Zhao,Guoqing Wang,Rangrang Fan,Bingwen Zou,Bo Han,Gang Guo
Traditional microtubule inhibitors fail to significantly enhance the effect of colorectal cancer; hence, new and efficient strategies are necessary. In this study, a supramolecular nanoreactor ( [email protected] 3+ ) based on tannic acid (TA), iron ion (Fe 3+ ), and docetaxel (DOC) with microtubule inhibition, reactive oxygen species (ROS) generation, and glutathione peroxidase 4 (GPX4) inhibition, is prepared for ferroptosis/apoptosis treatment. After internalization by CT26 cells, the [email protected] 3+ nanoreactor escapes from the lysosomes to release payloads. The subsequent Fe 3+ /Fe 2+ conversion mediated by TA reducibility can trigger the Fenton reaction to enhance the ROS concentration. Additionally, Fe 3+ can consume glutathione to repress the activity of GPX4 to induce ferroptosis. Meanwhile, the released DOC controls microtubule dynamics to activate the apoptosis pathway. The superior in vivo antitumor efficacy of [email protected] 3+ nanoreactor in terms of tumor growth inhibition and improved survival is verified in CT26 tumor-bearing mouse model. Therefore, the nanoreactor can act as an effective apoptosis and ferroptosis inducer for application in colorectal cancer therapy.
研究领域:
肿瘤学
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纳米技术
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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
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