Oncology Letters
·
2017
·Vol. 14
·期 5
·5307-5312
·
IF 1.39
Binggao Wang,Zhibo Xing,Fengmei Wang,Xinyan Yuan,Yanhui Zhang
In order to improve outcomes after breast cancer treatment, it is essential to understand the mechanisms of action of potential therapeutic agents. The effect of fangchinoline (FAN) on migration and apoptosis of human breast cancer MDA-MB-231 cells and its underlying mechanisms were investigated. MDA-MB-231 cells were treated with different concentrations of FAN, growth inhibition rates were measured by MTT assay and morphological changes of apoptotic cells were observed by Hoechst staining. The wound-healing assay was used to determine of the effect of FAN on the migration of MDA-MB-231 cells. ELISA was used to detect the expression of MMP-2 and -9 in MDA-MB-231 cells treated with different concentrations of FAN and western blot analysis was used to quantify expression of NF-κβ and Iκβ proteins in the same cells. Our results showed that FAN significantly inhibited the growth of MDA-MB-231 cells in concentration-dependent manner and it induced MDA-MB‑231 cell apoptosis. With the high FAN concentrations and long exposure times, the levels of MMP-2 and -9 decreased and the expression of NF-κβ decreased, while the expression of Iκβ protein increased. Based on these results, the antitumor effects of FAN on breast cancer cells can be explained at least partially by inducing apoptosis and inhibiting the migration of MDA-MB-231 cells.
研究领域:
肿瘤学
·
药理学
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细胞生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2021
·Vol. 22
·期 21
·11466
·
IF 5.924
Miaomiao Qi,Xiang Liu,Ying Zhou,Haoyu Wang,Ying Zhao,Jing Ren,Jin Xiang
G protein-coupled estrogen receptor 1 (GPER1) is a potential therapeutic target for treating triple-negative breast cancers (TNBC). However, modulators for GPER1 that can be used to treat TNBC have not appeared. Berberine (BBR) is a bioactive isoquinoline alkaloid with high oral safety. In recent years, BBR has shown an inhibitory effect on TNBC tumors such as MDA-MB-231, but the molecular target remains unclear, which hinders related clinical research. Our work proved that BBR is a modulator of GPER1 that can inhibit cell viability, migration, and autophagy of MDA-MB-231 cells. The inhibitory effect of BBR on MDA-MB-231 cells has a dependence on estrogen levels. Although BBR promoted the proteasome, which is a major factor in the degradation of GPER1, it could still induce the protein level of GPER1. Correspondingly, the transcription of cellular communication network factor 2 (CCN2) was promoted. BBR could bind to GPER1 directly and change the secondary structure of GPER1, as in the case of 17β-estradiol (E2). In addition, BBR induced not only a high degree of co-localization of GPER1 and microtubule-associated protein 1 light chain 3 (MAP1LC3), but also the accumulation of sequestosome 1 (SQSTM1/p62) by the inhibition of the nuclear translocation of the nuclear factor-kappa B (NF-κB) subunit (RELA/p65), which indicates NF-κB inhibition and anti-cancer effects. This result proved that the promotional effect of BBR on the GPER1/NF-κB pathway was closely related to its inhibitory effect on autophagy, which may serve as a new mechanism by which to explain the inhibitory effect of BBR on MDA-MB-231 cells and expand our understanding of the function of both BBR and GPER1.Keywords:berberine;binding;co-localization;GPER1;MAP1LC3;NF-κB
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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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2019
·
IF 3.973
Lingli Zhang,Chengguang Wu,Shansong Mu,Wei Xue,Dong Ma
To enhance the chemotherapy effect to MDA-MB-231, a glutathione (GSH)-sensitive amphiphilic hyperbranched poly (amide-amine) (mPEG-PLGA-HPAA) was synthesized, and the anti-cancer drug, paclitaxel (PTX) was then encapsulated into the mPEG-PLGA-HPAA micelles. The mPEG-PLGA-HPAA containing a large number of disulfide bonds could degrade and then consume the GSH intracellularly, which was expected to enhances the sensitivity of MDA-MB-231 cells to PTX. It was found that the mPEG-PLGA-HPAA/PTX nanoparticles could respond to the GSH and showed a GSH-controlled PTX release. Simultaneously, the mPEG-PLGA-HPAA/PTX nanoparticles significantly enhanced the efficacy of PTX by inhibiting MDA-MB-231 cells proliferation and inducing cells apoptosis, performing the self-sensitization effect of chemotherapy. Moreover, the drug carrier of mPEG-PLGA-HPAA exhibited excellent biocompatibility in vitro and in vivo . These results indicated that the self-sensitized drug carrier is a promising route to maximize the therapeutic effect and minimize the side effects of chemotherapy drugs used currently in clinical.
研究领域:
药学
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肿瘤学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Heliyon
·
2024
·
IF 3.4
Wen-Juan Tang,Di Xu,Ming-Xing Liang,Guan-Qun Wo,Wen-Quan Chen,Jin-Hai Tang,Wei Zhang
Triple-negative breast cancer (TNBC) is more prone to recurrence and metastasis relative to other subtypes of breast cancer, leading to an extremely poor prognosis. The increasing potential chemoresistance of TNBC patients is mainly due to that tumor cells escape from apoptosis. In recent years, statins have demonstrated extensive anti-tumor effects. It is worth noting that statins have more effective anti-tumor effects on TNBC cells and drug-resistant breast cancer cells. Therefore, this study examines the superior cytotoxic effects of statins on TNBC cell lines and further explores their potential therapeutic mechanisms. We detected different cell phenotypes and found that statins significantly reduced the cell viability of TNBC cells. Specifically, pitavastatin showed an obvious induction in cell death, cell cycle arrest and oxidative stress in TNBC MDA-MB-231 cells. The reversal effect of iron chelator desferrioxamine (DFO) on the morphological and molecular biological changes induced by pitavastatin has revealed a new mode of cell death induced by pitavastatin: ferroptosis. This ferroptotic effect was strengthened by the decreased expression of glutathione peroxidase 4 (GPx4) as well as newly discovered ferroptosis suppressor protein 1 (FSP1). The data showed that ferroptotic death of MDA-MB-231 cells is autophagy-dependent and mediated by the mevalonate pathway. Finally, we found that therapeutic oral doses of statins can inhibit the growth of transplanted tumors, which establishes statins as a potential treatment for TNBC patients. In conclusion, we found pitavastatin could induce autophagy-dependent ferroptosis in TNBC cells via the mevalonate pathway which may become a potential adjuvant treatment option for TNBC patients.
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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癌症研究
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DOI
PubMed
高影响因子
JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2020
·Vol. 72
·期 7
·969-978
·
IF 2.571
Ding Ting,Yang Luo-Jie,Zhang Wei-Dong,Shen Yun-Heng
ObjectivesTo screen the cytotoxic activity of six secondary metabolites isolated from soil fungus Aspergillus niger. Importantly, to investigate the mechanism that pyoluteorin induced human triple-negative breast cancer MDA-MB-231 cells apoptosis in vitro.MethodsThe cell viability assay was tested with CTG assay. Cell cycle, apoptosis and intracellular reactive oxygen species (ROS) production assay were tested with flow cytometry. Additionally, intracellular ROS production assay and mitochondrial membrane potential assay were determined with laser scanning confocal microscopy. The expression of apoptosis-related proteins was determined with Western blot.Key findingsPyoluteorin displayed significantly selective cytotoxicity against human triple-negative breast cancer MDA-MB-231 cells (IC50 = 0.97 µm) with low toxicity against human breast epithelial cell MCF-10A. It was found that pyoluteorin could arrest MDA-MB-231 cells cycle at G2/M phase and induce cell apoptosis. Further experiments demonstrated that the apoptosis-inducing effect of pyoluteorin was related to reduction of mitochondrial membrane potential, accumulation of ROS and change of apoptosis-related protein expressions.ConclusionOur studies revealed that pyoluteorin had potent proliferation inhibition against MDA-MB-231 cells through arresting cell cycle at G2/M phase and inducing caspase-3-dependent apoptosis by mitochondrial pathway, implying that pyoluteorin may be a potential lead compound for drug discovery of human triple-negative breast 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
CHEMISTRY & BIODIVERSITY
·
2023
·Vol. 20
·期 4
·e202200523
·
IF 2.9
Zhonghua An,Xuelin Feng,Mengjia Sun,Yifan Wang,Hongbo Wang,Yanling Gong
Chamomile essential oil (CEO) is extracted from chamomile and mainly used in aromatherapy. The chemical constituents and its antitumor activity on Triple-negative breast cancer (TNBC) was explored in the present study. Gas chromatography-mass spectrometry (GC/MS) was employed to analyze the chemical constituents of CEO. The cell viability, migration and invasion of TNBC cell MDA-MB-231 were measured using MTT, wound scratch and Transwell assay, respectively. The protein expression of PI3K/Akt/mTOR signaling pathway was determined by Western blot. CEO is rich in terpenoids (63.51 %), among which the identified terpenoids and their derivatives are mainly Caryophyllene (29.57 %), d-Cadinene (12.81 %), Caryophyllene oxide (14.51 %), etc. Three concentration of CEO (1, 1.5, 2 μg/mL) significantly inhibited the proliferation, migration and invasion of MDA-MB-231 cells with a dose dependent manner. Moreover, the phosphorylation of PI3K, Akt and mTOR was inhibited by CEO. The results revealed that there was abundant terpenoids in the CEO which account for 63.51 %. CEO significantly inhibited the proliferation, migration and invasion of MDA-MB-231 cells, exhibiting antitumor effect on TNBC. The antitumor effect of CEO might attribute to its inhibition on PI3K/Akt/mTOR signaling pathway. However, further study should be conducted in more TNBC cell lines and animal models to provide further evidence for TNBC treatment by CEO.
研究领域:
肿瘤学
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药理学
·
分子生物学
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细胞生物学
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分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2020
·
IF 7.1
Xin Liu,Dawei Fan,Chenchen Zhang,Xinrong Shao,Hongmin Ma,Yong Zhang,Xueying Wang,Qin Wei,Huangxian Ju
An ultrasensitive photoelectrochemical (PEC) antifouling immunosensor was proposed using BiOBr/FeTPPCl/BiOI as matrix and polyacrylic acid (PAA)/polyethylene glycol (PEG) as hybrid antifouling interface for MDA-MB-231 detection. An indium tin oxide (ITO) electrode was successively modified with bismuth oxybromide (BiOBr) with layered crystal structure, which was sensitized with tetraphenyl iron(Ⅲ) porphyrin chloride (FeTPPCl) to widen the absorption range of visible light, and decorated with bismuth oxyiodide (BiOI) nanosheets to improve the PEC response. The joint action of PAA and PEG could offset the adsorption of non-specific proteins on the immunosensing interface for obtaining good antifouling performance. Based on the specific interaction of sialic acid (SA) on the cytomembrane with 3-aminophenylboronic acid (APBA), and the synergistic antifouling effect of PEG and PAA, a simple PEC immunosensing method was developed for the quantitative determination of MDA-MB-231 cells. This proposed antifouling PEC immunosensor exhibited a wide linear range (1 × 10 2 ∼ 1 × 10 6 cells·mL -1 ) and a low detection limit (30 cells·mL -1 ). The development of antibody-free immunosensors may improve the application for the diagnosis of human breast cancer.
研究领域:
材料科学
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分析化学
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生物化学
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癌症诊断
✓ 已验证
产品关联
DOI
高影响因子
Cancer Medicine
·
2020
·Vol. 9
·期 7
·2564-2578
·
IF 3.491
Yubo Guo,Yingyi Fan,Xiaohua Pei
Triple-negative breast cancer (TNBC) is a basal-like cancer which is considered to be more intrusive, have a poorer prognosis and chemoresistance. TNBC is characterized by the presence of epithelial to mesenchymal transition (EMT) that plays a major role in the progression of the cancer. In the present study, we first use a classic prescription of Chinese medicine Fangjihuangqi Decoction to treat TGFβ1-induced MDA-MB-231 cells in vitro. Our data showed that TGFβ1-induced MDA-MB-231 cell morphology change, promoted MDA-MB 231 invasion, increased Vimentin expression, and decreased E-cadherin expression. Further, Fangjihuangqi Decoction-medicated serum (FHS) treated both MDA-MB 231 cells and TGFβ1-induced MDA-MB-231 cells. Results showed that Fangjihuangqi Decoction could inhibit cell proliferation, reduce cell invasion, increase E-cadherin expression, and decrease EMT markers. Secondly, we established a xenograft tumor zebrafish model to assess Fangjihuangqi Decoction inhibition of cancer cell proliferation and invasion. Our results indicated that Fangjihuangqi Decoction could inhibit tumor growth, restrain the sprouts number of tumor neovascularization, and reduce the length of tumor neoplastic lymphatics by increasing E-cadherin expression and decreasing EMT markers in TNBC xenograft tumor zebrafish model. Overall, our studies provide evidences that Fangjihuangqi Decoction could inhibit TNBC, reverse EMT, and contribute to antimetastasis by increasing E-cadherin expression and decreasing EMT markers, which provide an experimental basis for clinical application of Fangjihuangqi Decoction on TNBC treatment.
研究领域:
肿瘤学
·
药理学
·
分子生物学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Ming Ying,Qin Li,Jingbo Wu,Yihang Jiang,Zhourui Xu,Mingze Ma,Gaixia Xu
Breast cancer is characterized by the uncontrolled proliferation of breast epithelial cells under the action of a variety of carcinogens. Although HER2-inhibitors were currently applied for HER2-positive breast cancer patients, they didn’t work for patients with resistance to HER2-targeted anti-cancer drugs. In this work, we prepared novel CuS@BSA-NB2 nanoparticles (NPs) for breast cancer photothermal therapy (PTT). The NPs had good biocompatibility due to the Bovine Serum Albumin (BSA) encapsulating and excellent targeting to HER2 because of nanobody 2 (NB2). Under 808 nm laser irradiation, CuS@BSA-NB2 NPs had high photothermal conversion efficiency and photothermal stability. Meanwhile, we constructed a stable cell line of MDA-MB-231/HER2 with a high expression of HER2 protein. Immunofluorescence and ICP-MS assays showed that CuS@BSA-NB2 NPs can be specifically enriched and be ingested in MDA-MB-231/HER2 cells. Furthermore, CuS@BSA-NB2 NPs had shown a more significant photothermal treatment effect than CuS@BSA under certain treatment conditions for MDA-MB-231/HER2. In addition, the cytotoxicity assay demonstrated that CuS@BSA-NB2 NPs had a low toxicity for MDA-MB-231/HER2 cells. The above results suggested that CuS@BSA-NB2 NPs were great photothermal therapeutic agents to reduce the malignant proliferation of breast epithelial cells and have potential for breast cancer therapy.Keywords: CuS@BSA-NB2 nanoparticles, photothermal therapy, HER2, NB2, MDA-MB-231/HER2
研究领域:
癌症研究
·
纳米技术
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2025
·
IF 6.8
Wei Wu,Jiaen Huang,Yuling Li,Jiaxi Chen,Xiaowei Kuang,Manzhen Ye,Rui Chen,Junli An,Zunnan Huang,Jing Sun
Cancer immunotherapy has revolutionized oncology by leveraging host immunity to eliminate malignant cells. In this study, five iridium(III) complexes (Ir1–Ir5) were synthesized and evaluated for their in vitro antitumor activity against various tumor cell lines. Among these, Ir4 and Ir5 exhibited the highest cytotoxicity and the most rapid cellular uptake in MDA-MB-231 cells. Colocalization experiments confirmed their accumulation in the endoplasmic reticulum (ER) and their ability to induce pyroptosis. Additionally, both complexes triggered ER stress, leading to increased calreticulin exposure on the cell surface, high-mobility group box 1 secretion, and ATP release, which collectively promoted immunogenic cell death. In vivo, a triple-dose Ir4 vaccine regimen significantly suppressed tumor growth compared to other treatment groups. These findings highlight the potential of Ir4-based novel triple-dose vaccination as a promising cancer immunotherapy strategy.
研究领域:
肿瘤学
·
免疫学
·
生物化学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Natural Product Communications
·
2022
·
IF 1.496
Ruolan Yang,Jingjing Ma,Hui Guo,Qinghua Meng,Yuwei Wang,Hao Yan,Ruyi Jin,Zhi Li,Lingjie Meng
MS, and IR, 1H NMR and 13C NMR spectroscopy were employed to elucidate 4 novel evodiamine (EVO) derivatives with nitro, amino, and methoxy groups, namely 2-NO2-EVO (7a), 10-OCH3-2-NO2-EVO (7b), 2-NH2-EVO (8a), and 10-OCH3-2-NH2-EVO (8b). The amino compounds (8a, 8b) were obtained by the reduction of nitro derivatives (7a, 7b) with SnCl2/HCl. The antiproliferative activities of these compounds were tested by Cell Counting Kit-8 assay for 48 h against the MDA-MB-231 and sw620 cancer cell lines, as well as the normal LO2 cells. The in vitro experiment showed that 8a possesses the most potent inhibitory activities against MDA-MB-231 and SW620 cells, with IC50 values of 0.79 and 1.28 μM, respectively. The cytotoxicity of 8a against the 2 cancer cell lines was higher than that of EVO.
研究领域:
药物化学
·
肿瘤学
·
有机合成
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF THE INDIAN CHEMICAL SOCIETY
·
2025
·
IF 3.4
Xinxin Zhou,Yicheng Mei,Baowei Yang,Jing Wang,Huiling Tang,Xiaolong Zhang,Changchun Liu
Eight 4-(morpholinyl arylamino)quinazoline-6-carbamoyl carboxylic acid methyl esters and four 4-(morpholinyl arylamino)quinazoline-6-carbamoyl hydroxamic acid derivatives were designed and synthesized by integrating morpholine moieties into the 4-aminoquinazoline scaffold, with additional modifications at the 6-position of quinazoline ring. The antitumor potential of these twelve derivatives was evaluated against human lung cancer A549 cells and breast cancer MDA-MB-231 cells using the Cell Counting Kit-8 (CCK-8) proliferation assays. The bioassay results indicated that most of the derivatives exhibited moderate to potent in vitro antiproliferative activity against both cancer cells. Particularly, compound 7bb demonstrated superior potency against MDA-MB-231 cells and A549 cells, with half maximal inhibitory concentration (IC 50 ) values of 4.286 and 4.720 μM, respectively, compared to the reference drug afatinib (IC 50 = 7.640 and 5.173 μM, respectively). This study provides valuable insights for the development of novel antitumor agents based on the 4-aminoquinazoline scaffold.
研究领域:
药物化学
·
肿瘤学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）