Journal of Medical and Biological Engineering
·
2024
·
IF 1.6
Shakila Baby,Muruganantham Bharathi,Sukumar Kalpana,Hirad Abdurahman Hajinur,Alarfaj Abdullah A.,Hussein-Al-Ali Samer Hasan,Surya Parthasarathy
Purpose To develop a drug delivery system (DDS) that is responsive to pH, redox conditions, and near-infrared (NIR) irradiation for the treatment of lung cancer. Methods The DDS was constructed by encapsulating cabazitaxel (CTX) into mesoporous silica nanoparticles (MSNs), which were then coated with polydopamine (PDA). Graphene oxide (GO) nanosheets were added to enhance the photothermal conversion efficiency. The system was further modified with hydrogels made from carboxymethyl cellulose (CMC) and l-Cysteine (IC) co-encapsulating curcumin (Cur) through an amidation reaction. The final product, CTX/GO@PDA@MSNs/Cur/CLC, was tested for cytotoxicity against human lung H1299 cancer cells. Apoptosis in treated cells was analyzed by flow cytometry. Results The developed DDS demonstrated effective inhibition of H1299 lung cancer cell growth. Cytotoxicity assays and flow cytometry confirmed apoptosis progression in cells treated with the DDS. Conclusion The tri-responsive DDS shows promise as an effective delivery system for cabazitaxel and curcumin in the treatment of lung cancer, inhibiting cancer cell growth through mechanisms responsive to pH, redox, and NIR irradiation.
研究领域:
药学
·
纳米技术
·
癌症研究
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
Cancer Management and Research
·
2025
·
IF 2.6
Mengzhu Chen,Jian Li,Shaodan Hu,Yuhan Wang,Keju Wang,Tan Wang
Background Lung cancer has high incidence and mortality rates. In consideration of the high toxicity and side effects of traditional chemical drugs and drug resistance, researchers have substituted some natural products for anti-lung cancer drugs. Ziziphi spinosae semen (ZSS) is a famous traditional Chinese herb, and ZSS-based formulas have been used against lung cancer in clinic, such as Xiaoyi Sanjie Formula. Jujuboside B (JUB) is one of the main bioactive components in ZSS; however, JUB’s roles in the treatment of lung cancer, and the mechanism have not been well reported.Objective This study intends to evaluate the effects of JUB on the proliferation and migration of non-small cell lung cancer H1299 cells (NC-1299 cells), as well as the potential related regulatory mechanism.Methods The viability, migration and invasive ability of NC-1299 cells were analyzed by CCK8, wound-healing, transwell invasion, and the expression of proteins was analyzed through Western blotting experiments.Results It showed that 160 and 320 μmol/L JUB significantly inhibited the proliferation of NC-1299 cells, reduced the cell migration in the wound healing test, and decreased the cell number of clonal assay (P < 0.05). JUB also significantly inhibited the expression of Vimentin, MMP2, and MMP9 proteins related to the migration and invasion of tumor cells, as well as inhibited the PI3K/AKT and Wnt/β-catenin pathways.Conclusion The results indicate JUB has a significant inhibitory effect on NC-1299 cells, and such inhibitory effect is associated with inhibiting the expression of migration and invasive proteins such as MMP2, as well as inhibiting the PI3K/AKT and Wnt/β-catenin pathways. The findings provide some references for the application of JUB in the substitution of anti-lung cancer drugs.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR BIOCHEMISTRY
·
2020
·Vol. 476
·期 2
·1075-1082
·
IF 2.795
Zhang Xiaowei,Dong Yu,Gao Miao,Hao Minfeng,Ren Hui,Guo Ling,Guo Hua
The tumor necrosis factor receptor-associated protein 1 (TRAP1) is associated with the occurrence and development of various diseases, including inflammation and cancer. However, the role and mechanism of TRAP1 in the development of lung cancer need to be further explored. Therefore, the purpose of this study is to investigate the role of TRAP1 in the regulation of apoptosis by cisplatin and its special mechanism. The RT-qPCR and Western blot were used to detect the mRNA and protein expression of ANGPTL4 in A549 and H1299 cells, respectively. And the cell apoptosis and cell cycle were measured by flow cytometry (FCM). The expression of genes related to apoptosis and drug resistance as well as the cell cycle regulators, including MDM2, CyclinB1, and CDK1, were detected by Western blot. Finally, the reactive oxygen species (ROS) indicator DCFH-DA was performed to detect the generation of ROS, and the mitochondrial membrane potential (ΔΨm) was detected by JC-1 staining. The results showed that the expression of TRAP1 was significantly increased in A549/DDP and H1299/DDP than A549 and H1299 cells. Further research found that knockdown of TRAP1 induced apoptosis and caused G2/M cell cycle arrest in A549/DDP and H1299/DDP cells. What is more, siTRAP1 reduced the relative JC-1 polymer monomer fluorescence ratio and decreased the ΔΨm, up-regulated the expression of Cytochrome C. Importantly, siTRAP1 induces ROS-dependent mitochondrial dysfunction. It is suggested that that TRAP1 suppresses cisplatin-induced apoptosis by promoting ROS-dependent mitochondrial dysfunction.
研究领域:
肿瘤学
·
细胞生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Huanchen Yao,Dayang Wang,Jiashuo Ye,Hailin Cong,Bing Yu
Ethnopharmacological relevance Lung cancer is a common respiratory cancer worldwide, which seriously threatens people's lives. The current treatment of lung cancer is not satisfactory. Traditional Chinese medicine records that Hedyotis diffusa Willd (HDW) has effects that include clearing heat and detoxifying, promoting diuresis and dehumidification, relieving pain and resolving masses, and exhibiting anti-cancer properties. It has shown extraordinary therapeutic value in the clinical practice of traditional Chinese medicine. It is commonly used to treat various tumors, inflammation, and other diseases. Aim of the study The purpose of this experiment is to isolate the components with anti-lung cancer effects from HDW and to explore its anti-lung cancer effect and mechanism through network pharmacology and in vitro cell experiments in order to find more effective and less side effects—anticancer drugs. Materials and methods We used ethanol to extract HDW preliminarily and then used ethyl acetate, n-butanol, petroleum ether, and water to extract it, obtaining the ethyl acetate fraction with the highest inhibition rate on lung cancer H1299 cells. The silica gel column purification, TOF, and nuclear magnetic resonance analysis yielded the Fisetin, which has an inhibitory effect on H1299 cells. The mechanism and application of Fisetin in inhibiting lung cancer were explored by network pharmacology and in vitro cell experiments. Results Using network pharmacology to explore the mechanism of Fisetin inhibiting lung cancer, 115 Fisetin targets, and 26,857 lung cancer targets were obtained, and 90 GO functions and 19 KEGG pathways were obtained (P < 0.01). Molecular docking results demonstrated that target protein-drug binding was stable. Afterward, the toxicity of Fisetin to H1299 cells was verified by in vitro cell experiments. MTT, live-dead staining, and confocal microscopy all showed that Fisetin had a good inhibitory effect on H1299 cells and had good cell compatibility. Through Western blot analysis, Fisetin can reduce the protein content of PI3K, MTOR, HIF1A and VEGFA. And it can reduce the mRNA expression levels of HIF1A and VEGFA. Moreover, Fisetin can also increase the expression of tumor suppressor molecule PTEN protein and mRNA in H1299 cells. Conclusions Fisetin and HDW can successfully stop lung cancer H1299 cells from growing. The mechanism of Fisetin may be related to the inhibition of PI3K/MTOR/HIF1A/VEGFA signaling pathway.
研究领域:
药理学
·
肿瘤学
·
生物信息学
·
细胞生物学
·
药物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Omega
·
2024
·
IF 3.7
Tengjiao Fan,Lin Shen,Yaxin Huang,Xin Wang,Lijiao Zhao,Rugang Zhong,Peng Wang,Guohui Sun
Lung cancer ranks as the second most diagnosed cancer and the leading cause of cancer-related deaths worldwide. Novel chemotherapeutic strategies are crucial to efficiently target tumor cells while minimizing toxicity to normal cells. In this study, we proposed a combination strategy using energy blocker lonidamine (LND) and cytotoxic drug nimustine (ACNU, 1-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-3-(2-chloroethyl)-3-nitrosourea) to enhance the killing of a human lung cancer cell line and investigated the potential chemo-sensitizing mechanism of LND. LND was found to remarkably increase the cytotoxicity of ACNU to A549 and H1299 cells without significantly affecting normal lung BEAS2B cells. The combination of LND and ACNU also produced significant effects on cell apoptosis, colony formation, cell migration, and invasion assays compared to single drug treatment. Mechanistically, LND decreased intracellular ATP levels by inhibiting glycolysis and inducing mitochondrial dysfunction. Furthermore, the combination of LND and ACNU could intensify cellular oxidative stress, decrease cellular GSH contents, and increase reactive oxygen species (ROS) production. Notably, LND alone dramatically downregulated the expression of DNA repair protein MGMT (O6-methylguanine-DNA methyltransferase), enhancing DNA interstrand cross-link formation induced by ACNU. Overall, LND represents a potential chemo-sensitizer to enhance ACNU therapy through energy inhibition, disrupting redox homeostasis and downregulating MGMT expression in human lung cancer cell line under preclinical and clinical background.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2018
·Vol. 42
·期 6
·3093-3104
·
IF 2.784
Yang Zhou,Tao Hong,Li Tong,Wei Liu,Xueting Yang,Jianghan Luo,Fuling Wang,Jian Li,Lijun Yan
Non‑small cell lung carcinoma (NSCLC) is a life‑threatening malignancy. The level of the cell growth regulator mitogen‑activated protein kinase kinase kinase kinase 3 (MAP4K3) has been shown to be correlated with a high risk of NSCLC recurrence and poor recurrence‑free survival rate. The present study examined the effects of Astragalus polysaccharide (APS) and 10‑hydroxycamptothecin (HCPT), which are associated with marked suppression and dephosphorylation of the MAP4K3/mammalian target of rapamycin (mTOR) signaling pathway, in the H1299 NSCLC cell line. APS and HCPT decreased H1299 cell viability, induced apoptosis and altered the cell cycle stages, as evaluated using an 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide assay and flow cytometric analysis. Furthermore, APS increased the expression of apoptosis‑associated genes B‑cell lymphoma 2 (Bcl‑2) and Bcl‑2‑associated X protein (BAX), of proteases cysteine‑aspartic acid protease (caspase)‑3 and ‑9, and of cytochrome c. HCPT promoted autophagy in H1299 cells, with concomitant suppression of the expression of MAP4K3 and downregulation of mTOR signaling. Notably, combination treatment with the two agents reduced the migration and invasion of H1299 cells compared with the single treatments. It was also demonstrated that the overexpression of MAP4K3 promoted the migration and invasion of H1299 cells, and that the kinase activity was essential to this. These findings suggested that MAP4K3 may be an attractive target for the treatment of NSCLC.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Chemistry
·
2024
·
IF 3.8
Xu Xuemei,Zhu Zhaojingtao,Chen Siyu,Fu Yanneng,Zhang Jinxia,Guo Yangyang,Xu Zhouyang,Xi Yingying,Wang Xuebao,Ye Faqing,Chen Huijun,Yang Xiaojiao
Introduction: Cancer, a significant global health concern, necessitates innovative treatments. The pivotal role of chronic inflammation in cancer development underscores the urgency for novel therapeutic strategies. Benzothiazole derivatives exhibit promise due to their distinctive structures and broad spectrum of biological effects. This study aims to explore new anti-tumor small molecule drugs that simultaneously anti-inflammatory and anticancer based on the advantages of benzothiazole frameworks.Methods: The compounds were characterized by nuclear magnetic resonance (NMR), liquid chromatograph-mass spectrometer (LC-MS) and high performance liquid chromatography (HPLC) for structure as well as purity and other related physicochemical properties. The effects of the compounds on the proliferation of human epidermoid carcinoma cell line (A431) and human non-small cell lung cancer cell lines (A549, H1299) were evaluated by MTT method. The effect of compounds on the expression levels of inflammatory factors IL-6 and TNF-α in mouse monocyte macrophages (RAW264.7) was assessed using enzyme-linked immunosorbent assay (ELISA). The effect of compounds on apoptosis and cell cycle of A431 and A549 cells was evaluated by flow cytometry. The effect of compounds on A431 and A549 cell migration was evaluated by scratch wound healing assay. The effect of compounds on protein expression levels in A431 and A549 cells was assessed by Western Blot assay. The physicochemical parameters, pharmacokinetic properties, toxicity and drug similarity of the active compound were predicted using Swiss ADME and admetSAR web servers.Results: Twenty-five novel benzothiazole compounds were designed and synthesized, with their structures confirmed through spectrogram verification. The active compound 6-chloro-N-(4-nitrobenzyl) benzo[d] thiazol-2-amine (compound B7) was screened through a series of bioactivity assessments, which significantly inhibited the proliferation of A431, A549 and H1299 cancer cells, decreased the activity of IL-6 and TNF-α, and hindered cell migration. In addition, at concentrations of 1, 2, and 4 μM, B7 exhibited apoptosis-promoting and cell cycle-arresting effects similar to those of the lead compound 7-chloro-N-(2, 6-dichlorophenyl) benzo[d] thiazole-2-amine (compound 4i). Western blot analysis confirmed that B7 inhibited both AKT and ERK signaling pathways in A431 and A549 cells. The prediction results of ADMET indicated that B7 had good drug properties.Discussion: This study has innovatively developed a series of benzothiazole derivatives, with a focus on compound B7 due to its notable dual anticancer and anti-inflammatory activities. B7 stands out for its ability to significantly reduce cancer cell proliferation in A431, A549, and H1299 cell lines and lower the levels of inflammatory cytokines IL-6 and TNF-α. These results position B7B7 as a promising candidate for dual-action cancer therapy. The study’s mechanistic exploration, highlighting B7’s simultaneous inhibition of the AKT and ERK pathways, offers a novel strategy for addressing both the survival mechanisms of tumor cells and the inflammatory milieu facilitating cancer progression.
研究领域:
药理学
·
肿瘤学
·
药物化学
·
细胞生物学
·
炎症
✓ 已验证
DOI
PubMed
高影响因子
ACS Chemical Biology
·
2024
·
IF 3.5
Xiaorui Shi,Chong Hu,Liangli Fan,Bin Guo,Jingyu Zhang,Chu Tang,Fu Wang
MicroRNAs (miRNAs) play a significant role in tumor progression, and regulating miRNA expression with small molecules may offer a new approach to cancer therapy. Among them, miRNA-20b has been found to be dysregulated in several cancers, including nonsmall cell lung cancer (NSCLC). Herein, an in silico high-throughput computer screen was conducted to identify small molecules that downregulate miR-20b using the three-dimensional structure of the Dicer binding site on pre-miR-20b. Among 1058 small molecule compounds, Methotrexate (MTX), was discovered to be a potential miR-20b-specific inhibitor, which has been found to suppress miR-20b by specifically blocking Dicer processing in p53 wild-type A549 NSCLC cells but not in H1299 cells with p53 depletion. MTX effectively inhibited the proliferation, survival, migration, and invasion of A549 cells in a dose-dependent manner. Furthermore, the treatment of MTX up-regulated the expression of miR-20b target genes PTEN, STAT3, and HIF1α. Notably, MTX also significantly inhibited tumor growth in a mouse xenograft tumor model of NSCLC, with no observed tissue toxicity. Our findings indicate that MTX may have a novel role as an established drug in p53 wild-type NSCLC tumor therapy by down-regulating miR-20b expression. These findings are expected to provide preclinical evidence for miR-20b-targeting NSCLC therapeutic strategies.
研究领域:
肿瘤学
·
分子生物学
·
药理学
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOSCIENCE REPORTS
·
2021
·Vol. 41
·期 10
·
IF 3.84
Wang Yingying,Hou Yongqiang,Hou Lanjiao,Wang Wei,Li Ke,Zhang Zhe,Du Bo,Kong Dexin
Lung cancer remains the leading cause of cancer mortality because of its metastatic potential and high malignancy. The discovery of new applications for old drugs is a shortcut for cancer therapy. We recently investigated the antitumor effect of digoxin, a well-established drug for treating heart failure, against nonsmall cell lung cancer A549 and H1299 cells. Digoxin inhibited the proliferation and colony-forming ability of the two cell lines and arrested the cell cycle at the G0/G1 phase in A549 cells and the G2/M phase in H1299 cells. Mitochondria-mediated apoptosis was induced in A549 cells but not in H1299 cells after treatment with digoxin. Moreover, digoxin inhibited the migration, invasion, adhesion and epithelial–mesenchymal transition of A549 and H1299 cells. Autophagy was induced in both cell lines after treatment with digoxin, with an increase in autophagosome foci. In addition, digoxin inhibited the phosphorylation of Akt, mTOR and p70S6K, signaling molecules of the PI3K/Akt pathway that are known to be involved in tumor cell survival, proliferation, metastasis and autophagy. Our findings suggest that digoxin has the potential to be used for therapy for human nonsmall cell lung cancer, but further evidence is required.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
·
2022
·Vol. 19
·期 4
·e202100910
·
IF 2.745
Chunlian Li,Qiuyang Cai,Xianyi Wu,Zekai Tan,Shiyuan Huang,Chuqi Wei,Weicheng Zhang,Zhuoyu Chen,Lanyue Zhang,Hongping Xiang
Species of the genus Citrus are cultivated in many regions of China and are widely used for medicinal purposes. In the present study, essential oils (EOs) were extracted from four different Citrus species using steam distillation. The chemical components of these four essential oils were separated using gas chromatography-mass spectrometry, and 52 compounds were confirmed. D-limonene was found to be the most abundant compound. All four essential oils demonstrated varied but remarkable radical scavenging capacity (IC 50 ; 0.77–13.9 %). Citrus paradisi essential oil exhibited excellent antioxidant activity. Compared to ibuprofen, topical application of the four Citrus spp. essential oils significantly inhibited ear edema formation in mice. Furthermore, essential oils from the four Citrus species reduced the expression levels of interleukin-6 (IL-6), cyclooxygenase-2 (COX-2) and nuclear transcription factor kappa B p65 (NF-κB) to different degrees. The cytotoxicity of the four essential oils on BV 2 microglial cells was determined using the MTT assay (IC 50 ; 321.37–1558.87 μg/mL), wherein Citrus limon essential oil showed the lowest cytotoxicity. The essential oils of Citrus limon , Citrus reticulata , and Citrus paradisi had an inhibitory effect on the lung cancer cell lines H1299 by inducing a G0/G1 cell cycle arrest. Cluster and principal component analyses were used to determine the relationship among the Citrus species. These results suggest that the four Citrus essential oils have potential for use as active ingredients in functional foods or cosmeceutical products. Graphical
研究领域:
药理学
·
生物化学
·
植物科学
·
药物化学
✓ 已验证
DOI
PubMed
高影响因子
KAOHSIUNG JOURNAL OF MEDICAL SCIENCES
·
2023
·
IF 3.3
Peng-Cheng Zhong,Zhi-Wen Liu,Qi-Chang Xing,Jia Chen,Rui-Pei Yang
Non-small cell lung cancer (NSCLC) accounts for ~85% of all lung cancer cases. Neferine is used as a traditional Chinese medicine with many pharmacological effects, including antitumor properties; however, it has not been reported whether neferine plays an anticancer role by causing pyroptosis in NSCLC cells. We used two typical lung cancer cell lines, A549 and H1299, and 42 lung cancer tissue samples to investigate the regulatory effects of neferine on TGF-β and MST1. We also treated lung cancer cells with different concentrations of neferine to study its effects on lung cancer cell survival, migration, invasion, and epithelial–mesenchymal transition (EMT) as well as on pyroptosis. Lentivirus-mediated gain-of-function studies of TGF-β and MST1 were applied to validate the roles of TGF-β and MST1 in lung cancer. Next, we used murine transplanted tumor models to evaluate the effect of neferine treatment on the metastatic capacity of lung cancer tissues. With increasing neferine concentration, the viability, migration, invasion, and EMT capacity of A549 and H1299 cells decreased, whereas pyroptosis increased. Neferine repressed TGF-β expression to modulate the induction of reactive oxygen species (ROS) by MST1. Overexpression of TGF-β in either in vitro or mouse-transplanted A549 cells restored the inhibitory effect of neferine on tumor development. Overexpression of MST1 clearly enhanced pyroptosis. Neferine contributed to pyroptosis by regulating MST1 expression through downregulation of TGF-β to induce ROS formation. Therefore, our study shows that neferine can serve as an adjuvant therapy for NSCLC patients.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMACOLOGICAL RESEARCH
·
2019
·
IF 5.574
Jin-Feng Teng,Da-Lian Qin,Qi-Bing Mei,Wen-Qiao Qiu,Rong Pan,Rui Xiong,Ya Zhao,Betty Yuen-Kwan Law,Vincent Kam-Wai Wong,Yong Tang,Chong-Lin Yu,Feng Zhang,Jian-Ming Wu,An-Guo Wu
Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Our previous studies have proven that Trillium tschonoskii Maxim. (TTM), a traditional Chinese medicine , possesses potent anti-tumor effect. However, the detailed components and molecular mechanism of TTM in anti-NSCLC are still unknown. In the present experiment, polyphyllin VI (PPVI) was successfully isolated from TTM with guidance of the anti-proliferative effect in A549 cells, and the cell death of PPVI treated A549 and H1299 cells was closely linked with the increased intracellular ROS levels. In addition, PPVI induced apoptosis by promoting the protein expression of Bax/Bcl2, caspase-3 and caspase-9, and activated autophagy by improving LC3 II conversion and GFP-LC3 puncta formation in A549 and H1299 cells. The mechanism study found that the activity of mTOR which regulates cell growth, proliferation and autophagy was significantly suppressed by PPVI. Accordingly, the PI3K/AKT and MEK/ERK pathways positively regulating mTOR were inhibited, and AMPK negatively regulating mTOR was activated. In addition, the downstream of mTOR, ULK1 at Ser 757 which downregulates autophagy was inhibited by PPVI. The apoptotic cell death induced by PPVI was confirmed, and it was significantly suppressed by the overexpression of AKT, ERK and mTOR, and the induced autophagic cell death which was depended on the Atg7 was decreased by the inhibitors, such as LY294002 (LY), Bafilomycin A1 (Baf), Compound C (CC) and SBI-0206965 (SBI). Furthermore, the mTOR signaling pathway was regulated by the increased ROS as the initial signal in A549 and H1299 cells. Finally, the anti-tumor growth activity of PPVI in vivo was validated in A549 bearing athymic nude mice . Taken together, our data have firstly demonstrated that PPVI is the main component in TTM that exerts the anti-proliferative effect by inducing apoptotic and autophagic cell death in NSCLC via the ROS-triggered mTOR signaling pathway, and PPVI may be a promising candidate for the treatment of NSCLC in future.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
·
中药学
✓ 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）