TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2026
·
IF 3.6
Yihong Shen,Leping He,Chenglong Zheng,Dongmeng Liu,Zongmao He,Yuxia Zou,Guo-Sheng Wu,Chengwei He,Xiaofeng Wang,Ren-Bo Ding,Jiaolin Bao
Sertraline, a widely used antidepressant, has shown emerging anticancer activity, but its metabolic mechanism in colorectal cancer (CRC) remains unclear. In this study, we evaluated the in vivo antitumor effect of sertraline using a CT26 tumor-bearing BALB/c mouse model, and performed UPLC-MS-based untargeted metabolomics to characterize serum metabolic alterations. Our results found that sertraline significantly inhibited tumor growth in BALB/c mice and partially reversed tumor-associated metabolic disturbances. Notably, levels of arachidonic acid (AA), 11,12-epoxyeicosatrienoic acid (11,12-EET), and 12-KETE were markedly elevated in the tumor model group but shifted toward normal levels after sertraline treatment. Pathway analysis identified arachidonic acid metabolism as the most significantly affected pathway, and Western blot confirmed that sertraline downregulated ALOXE3 expression in both tumor tissues and CT26 cells. ROC analysis revealed that a panel of only two metabolites achieved an AUC of 0.845, demonstrating good discriminatory ability between the tumor model and sertraline-treated groups, while expanding to ten metabolites further improved the AUC to 0.975 (95% CI: 0.800–1.000). These findings suggest that sertraline exerts antitumor effects in CRC associated with metabolic remodeling of arachidonic acid metabolism and altered ALOXE3 expression, providing preclinical evidence supporting further investigation of sertraline as a potential drug-repurposing candidate for CRC.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
·
2023
·
IF 8.8
Ziyan Zhou,Dingding Wu,Hao Wu,Boming Fu,Xinhao Wang,Jingyi Ling,Xin Jin,Cheng Gu
Sertraline is one of the most commonly used antidepressant pharmaceuticals with ubiquitous distribution in the aqueous environment. However, the environmental behavior of sertraline in the co-presence of low-molecular-weight organic acid (LMWOA) and iron oxide mineral is still poorly understood. In this study, the photodegradation of sertraline was systematically investigated in a common photosensitizing system (ferrihydrite (Fh)-LMWOA). Six LMWOAs, including citrate acid (CA), tartrate acid (TA), malate acid (MA), lactate acid (LA), succinate acid (SA) and malonic acid (MOA) were chosen as the representatives. Our results implied that the different Fe 3+ dissolution rates would lead to rather different sertraline degradation patterns following the order of Fh-CA > Fh-TA > Fh-MA > Fh-LA > Fh-SA > Fh-MOA. The reaction was initiated by the interaction between LMWOA and Fh via ligand-promoted-dissolution mechanism. Furthermore, the Fe 3+ dissolution rates also showed a strong correlation with the metal-organic complexation constants, indicating that the photodegradation process is strongly related to the complexation ability of LMWOA with Fe 3+ . •OH, O 2 •- and CO 2 •- were detected, indicating that they contributed to the photodegradation of sertraline. •OH was demonstrated to be the dominant Reactive oxygen species (ROS) for the degradation of sertraline, and the detailed transformation pathways were proposed based on the product analysis and theoretical calculation. According to the ecological structure activity relationship estimation, the photodegradation products of sertraline possessed lower toxicity compared to the parent compound. These findings contribute to a more comprehensive understanding of the environmental fate of sertraline and evaluate its potential ecotoxicity in natural systems.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2024
·Vol. 29
·期 16
·3733
·
IF 4.2
Leping He,Yuxi Tian,Qingqing Liu,Jiaolin Bao,Ren-Bo Ding
Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide. It is important to discover new therapeutic regimens for treating CRC. Depression is known to be an important complication of cancer diseases. Repurposing antidepressants into anticancer drugs and exploring the combinational efficacy of antidepressants and chemotherapy are potentially good options for developing CRC treatment regimens. In this study, sertraline, an antidepressant drug, and paclitaxel, an anticancer drug, were chosen to study their antitumor effects in the treatment of colorectal cancer, alone or in combination, and to explore their underlying mechanisms. The data showed that sertraline exerted a dose-dependent cytotoxic effect on MC38 and CT26 colorectal cancer cell lines with IC50values of 10.53 μM and 7.47 μM, respectively. Furthermore, sertraline synergistically sensitized chemotherapeutic agent paclitaxel efficacy in CRC cells with combination index (CI) values at various concentrations consistently lower than 1. Sertraline remarkably augmented paclitaxel-induced autophagy by increasing autophagosome formation indicated by elevated LC3-II/I ratio and promoting autophagic flux by degrading autophagy cargo receptor SQSTM1/p62, which may explain the synergistically cytotoxic effect of sertraline and paclitaxel combination therapy on CRC cells. This study provides important evidence to support repurposing sertraline as an anticancer agent and suggests a novel combinational regimen for effectively treating CRC as well as in the simultaneous treatment of CRC and depression.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Therapeutics
·
2024
·
IF 3.7
Leping He,Xijun Guo,Wanrong Wang,Weifeng Xu,Xiaoli Feng,Yuanfeng Fu,Yuxi Tian,Zongmao He,Sulan Luo,Jiaolin Bao,Ren-Bo Ding
Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer-related death worldwide. More than 30% of CRC patients will experience treatment failure and tumor recurrence after standard-of-care treatment. Therefore, it is important to discover new therapeutic regimens for treating CRC. Repurposing existing clinically used drugs into new anticancer agents represents a feasible way and has become increasingly popular. In this study, the aim is to investigate the anticancer effect of sertraline on CRC and to elucidate its underlying mechanism. The data showed that sertraline exhibited a potent anticancer effect against CRC in vitro and in vivo. Sertraline inhibited Akt- and STAT3-mediated cell proliferation but do not affect several programmed cell deaths in CRC, such as apoptosis, pyroptosis, ferroptosis, and mitophagy. Meanwhile, sertraline induced autophagosome accumulation but blocked autophagic flux in CRC cells. Further investigations reveal that sertraline impeded late autophagic flux at the stage of autolysosomal degradation rather than autophagosome-lysosomal fusion in CRC. Furthermore, it is also demonstrated that sertraline synergistically sensitized chemotherapeutic agents against CRC. Overall, the study reveals the great potential of sertraline as a novel therapeutic candidate for CRC, which is worthy of further development in the future.
✓ 已验证
产品关联
DOI
高影响因子
ANALYTICAL CHEMISTRY
·
2025
·
IF 6.7
Qianqian Shang,Yangyang Liu,Menghan Hou,Zhuangzhuang Dong,Stig Pedersen-Bjergaard,Chuixiu Huang,Xiantao Shen
Commercialization of sample preparation techniques is crucial for ensuring standard operating procedures and routine analysis capability. However, current devices for liquid-phase microextraction (LPME) are usually homemade and hardly commercialized due to the storage difficulty of manually prepared supported liquid membranes (SLMs). To address this challenge, a novel strategy for automated formation of SLMs by molecular self-assembly was proposed in this study. Specifically, the SLM solvent was directly added into the aqueous acceptor solution and self-assembled into the pores of the polymeric membrane with the assistance of a surfactant, automatically forming the SLM (in situ SLM). The in situ SLM successfully formed during the initial phase of extraction and caused no delay of the mass transfer, which could rationally solve the storage difficulty for manually prepared SLMs. Based on this strategy, a mass-producible three-dimensional printed extraction device incorporated with the in situ SLM was developed for drug analysis in urine samples. Under optimal conditions, exhaustive extraction (recovery >85%) was attained using the electrical-assisted LPME (i.e., electromembrane extraction, EME). Finally, the electromembrane extraction–liquid chromatography–tandem mass spectrometry (EME-LC-MS/MS) method based on the in situ SLM was validated using spiked urine samples, showing satisfactory limits of detection (0.87–2.97 ng mL–1), accuracy (87–105%), precision (RSD ≤ 9%), and matrix effects (92–110%). In summary, this approach could further simplify the extraction process, ensure the standard operating procedures, and enhance operational robustness, which is essential for facilitating the commercialization and routine application of SLM-based microextraction techniques.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DIAMOND AND RELATED MATERIALS
·
2025
·
IF 5.1
Siyu Xu,Xiaoyu Li,Yueling Zhang,Danhong Zhang,Nan Gao
Boron-doped diamond (BDD) is suitable for use as an electrochemical analytical electrode for real-time detection because of its ultra-wide electrochemical potential window and low background current. However, the practical application of planar BDD electrodes is limited by their low conductivity, few active sites, and insufficient detection sensitivity, which need to be improved by surface modification. In this study, submicron carbon spheres (SMCS) were deposited on BDD substrate by a simple CVD method. The composite structure (SMCS/BDD) has a large specific surface area and high conductivity, which improves the sensitivity for drug detection. These results indicate that BDD-based all‑carbon materials have the potential to be used as electrodes for medical sensors.
✓ 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）