CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
·
2014
·Vol. 42
·期 2
·146-153
·
IF 2.405
Xiao-Yun Hu,Ji-Yun Liang,Xue-Jun Guo,Li Liu,Ya-Bing Guo
Summary The development of chemoresistance may reduce the efficacy of chemotherapeutic drugs for treating hepatocellular carcinoma (HCC). In the present study, the effects of apigenin on intensifying the chemosensitivity of HCC cells and an HCC xenograft model in response to 5-fluorouracil (5-FU) were investigated. Sub-toxic concentrations of apigenin (4 μ mol/L) significantly enhanced the cytotoxicity of 5-FU (100 μ g/mL) in HCC cells. In vivo , combined treatment with apigenin (20 mg/kg, five times/week for 3 weeks) and 5-FU (20 mg/kg for 5 consecutive days) significantly inhibited the growth of HCC xenograft tumours. Annexin V–propidium iodide dual staining assays, terminal deoxyribonucleotidyl transferase-mediated dUTP–digoxigenin nick end-labelling assays and western blotting analysis were used to confirm the synergistic effects of apigenin and 5-FU on HCC apoptosis. Coincubation of HCC cells with apigenin and 5-FU increased levels of reactive oxygen species (ROS), which was followed by a decrease in the mitochondrial membrane potential (ΔΨm). In addition, combined triggered the mitochondrial apoptotic pathway, as indicated by decreased Bcl-2 expression and loss of ΔΨm, with significant activation of caspase 3 and poly(ADP-ribose) polymerase. The present study is the first to demonstrate that apigenin may potentiate the cytotoxicity of 5-FU in HCC via inhibition of ROS-mediated drug resistance and concurrent activation of the mitochondrial pathways of apoptosis.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2015
·Vol. 11
·期 6
·4671-4677
·
IF 1.554
Qigen Du,Guang Xin,Hai Niu,Wen Huang
The 4[(Tetrahydro‑2H‑pyran‑2‑yl) oxy] phenol (XG‑d) hydroquinone analog, is found in Vaccinium vitis‑idaea L. Although it is known for its antioxidant properties and high level of safety, its antitumor activity remains to be elucidated. In the present study, the anticancer effect of XG‑d was determined in vitro and in vivo. The cytotoxicity of XG‑d against C26 murine colon carcinoma cells was found to occur in a time‑ and concentration‑dependent manner, whereas little effect was observed in the two normal cell lines (HK‑2 and L02) investigated. Oral administration of XG‑d (100 mg/kg) had effects on the tumor growth of tumor‑bearing mice. Furthermore, marked apoptosis was observed using Hoechst 33258 staining and flow cytometric analysis with annexin V/propidium iodide double staining. XG‑d also downregulated the expression of B‑cell lymphoma 2 (Bcl‑2), increased the expression levels of Bcl‑2‑associated X protein and activated caspase‑9, caspase‑3 and poly(adenosine diphosphate‑ribose) polymerase. The present study demonstrated for the first time, to the best of our knowledge, that XG‑d inhibited cancer cell growth via the induction of apoptosis and was also able to inhibit tumor growth in vivo. These results demonstrated that XG‑d may be used as a potential natural agent for cancer therapy with low toxicity.
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Qiang Chu,Ruoyi Jia,Wen Chen,Yangyang Liu,Yonglu Li,Xiang Ye,Yong Jiang,Xiaodong Zheng
Ethyl Carbamate (EC), as a carcinogen widely found in fermented foods, was verified that its cytotoxicity was associated with oxidative stress. Polysaccharides from natural sources due to their antioxidative capacity have attracted great attention in the past time. In this study, purified polysaccharide from Tetrastigma hemsleyanum vines (TVP) with 64.89 kDA was extracted and conducted multiple analysis to identify its structural information. It could be discovered that TVP was composed of mannose, rhamnose, glucuronic acid, glucose, galactose, and arabinose. In vitro , TVP could inhibit cytotoxicity and genotoxicity, attenuate oxidative damage and mitochondrial dysfunction induced by EC in Caco-2 cells. Meanwhile, TVP could suppress apoptosis by mTOR and Bcl-2 signaling pathways, ameliorate oxidative via Sirt1-FoxO1 and Nrf2-Keap1 signaling pathways. In vivo , EC as well triggered the decline of survival and athletic ability in Caenorhabditis elegans ( C. elegans ) and TVP could reverse the decline. In the meantime, TVP could ameliorate oxidative damage in N2 and daf-2 (-) mutant but fail in daf-16 (-) mutant, which suggested that DAF-16 (FOXO) might affect the antioxidative protection of TVP in C. elegans . In brief, our results manifested that TVP could attenuate EC-induced cytotoxicity both in vitro and in vivo .
研究领域:
药理学
·
毒理学
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2019
·
IF 3.571
Yuanhang Ren,Jiaxing Shi,Yangping Mu,Ke Tao,Hong Jin,Taiping Hou
To explore lead compounds for biological insecticides, nine fatty acids (FAs)' insecticidal activities against Helicoverpa zea (Lepidoptera, Noctuidae) and their cytotoxicity on H. zea neuronal cells (AW1 cells) were evaluated. The results showed that FAs at 1000 mg/L had a mortality rate of 10.0–83.33% and an inhibitory rate on AW1 cells with IC50 values of 74.6–287.37 μM. Particularly, lauric acid exhibited the most excellent bioactivity both in vivo and in vitro among nine FAs. Further, its mode of action was investigated on the AW1 cells, and the results showed that lauric acid induced apoptosis on the AW1 cells, involving a decrease of mitochondrial membrane potential (ΔΨm) and an increase of caspase-9/3 activity and reactive oxygen species (ROS) levels. Furthermore, by detecting the expression of apoptosis protein, we found that the levels of Bcl-2 fell whereas the levels of cytochrome c and Bax rose remarkably. These results showed that FAs such as lauric acid could be potential lead compounds with a novel mode of action and highly insecticidal activity against H. zea.
研究领域:
昆虫学
·
毒理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL RESEARCH
·
2020
·
IF 5.715
Jun Zhu,Lei Tang,Shanlei Qiao,Lijuan Wang,Yiming Feng,Li Wang,Qian Wu,Ping Ding,Zhan Zhang,Lei Li
Methylmercury (MeHg) is a ubiquitous environmental toxicant with neurotoxic effects. Although its neurotoxicity had been more studied, the role of gut microbiota remains unclear. In this study, adult zebrafish and larvae were exposed to MeHgCl at the dose of 0, 1 and 10 ng/mL. MeHgCl exposure impaired the locomotor activity via upregulation of apoptosis and autophagy related genes in the brain. Intestinal and cerebral metabolome indicated that phosphatidylinositol signaling system and inositol phosphate metabolism pathways were significantly impacted in adult zebrafish upon MeHgCl exposure. The levels of myo-inositol (MI) in the intestine and brain were decreased and positively correlated. 16 S rRNA sequencing data from adult zebrafish showed that MeHgCl exposure also shifted the structure of gut microbiota and reduced the relative abundance of Bacteroidetes and Proteobacteria , which were further identified at genus level as Aeromonas and Cetobacterium . Further functional analysis indicated that MeHgCl disrupted inositol phosphate metabolism of gut microbiota. Notably, MI supplementation restored the impairment of locomotor activity and inhibited the upregulation of apoptosis and autophagy related genes, such as bcl-2 and atg5 . Thus, this study not only revealed the key role of gut microbiota in MeHgCl-mediated neurotoxicity but also gave new insights into antagonizing its toxicity.
研究领域:
毒理学
·
神经科学
·
微生物学
·
代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2019
·Vol. 10
·期 4
·1816-1825
·
IF 3.241
Peng Wen,Teng-Gen Hu,Yan Wen,Robert J. Linhardt,Min-Hua Zong,Yu-Xiao Zou,Hong Wu
Phycocyanin (PC), a water-soluble biliprotein, exhibits potent anti-colon cancer properties. However, its application in functional foods is limited by the poor stability and low bioavailability of PC. In this study, we successfully encapsulated PC by coaxial electrospinning. The colon targeted release of PC was achieved with retention of the antioxidant activity of PC. The PC-loaded electrospun fiber mat (EFM) obtained inhibited HCT116 cell growth in a dose-dependent and time-dependent manner. In particular, the PC-loaded EFM exerted its anti-cancer activity by blocking the cell cycle at the G0/G1 phase and inducing cell apoptosis involving the decrease of Bcl-2/Bax, activation of caspase 3 and release of cytochrome c. This study suggests that co-axial electrospinning is an efficient and effective way to deliver PC and improve its bioavailability; thus, it represents a promising approach for encapsulating functional ingredients for colon cancer prevention.
研究领域:
药理学
·
生物技术
·
癌症研究
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOORGANIC & MEDICINAL CHEMISTRY
·
2024
·
IF 3.3
Li Guan,Yanxin Xia,Pengfei Song,Huiru Zhao,Shengjie Zhang,Wanzhen Su,Aiyun Li,Weize Li
In this paper, we investigated the anticancer effect and the mechanism of our newly synthesized bibenzyl 8Ae against human lung cancer A549 cells. Compound 8Ae could induce apoptosis by inhibiting the glycolysis in A549 cells. Hexokinase 2 (HK2), the first key enzyme in glycolysis process, was significantly down-regulated by 8Ae. Besides, compound 8Ae induced HK2 dissociated from mitochondria to cytosol, which could be induced by inhibiting the phosphorylation of Akt. In addition, 8Ae could induce mitochondrial-mediated apoptosis, and mitochondrial membrane potential (MMP) was decreased. After 8Ae treatment, the Bax/Bcl-2 ratio was increased and cytochrome c (Cyt c ) was release from mitochondria to cytosol. Molecular docking indicated that 8Ae have an interaction with HK2 by extending into acitve pockets of the protein to form stable hydrogen bonds. Additionally, 8Ae had significantly improved pharmacokinetic properties through the prediction, comparison, and analysis of the ADMET properties of 8Ae and moscatilin (MST). Taken together, 8Ae might inhibit glycolysis by stimulating the shedding of HK2 from mitochondria and promoting mitochondria-regulated apoptosis to inhibit the proliferation of A549 cells. This article provides a research basis for bibenzyl compounds as new small molecule drugs for lung cancer.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
NEUROCHEMICAL RESEARCH
·
2018
·Vol. 43
·期 7
·1439-1453
·
IF 2.772
Jia Jingjing,Zhang Ting,Chi Jieshan,Liu Xiaoma,Sun Jingjing,Xie Qizhi,Peng Sijia,Li Changyan,Yi Li
CeO 2 nanoparticles (nanoceria) have been used in many studies as a powerful free radical scavenger, and LXW7, a small-molecule peptide, can specifically target the integrin αvβ3, whose neuroprotective effects have also been demonstrated. The objective of this study is to observe the neuroprotective effect and potential mechanism of CeO 2 @PAA-LXW7, a new compound that couples CeO 2 @PAA (nanoceria modified with the functional group of polyacrylic acid) with LXW7 via a series of chemical reactions, in H 2 O 2 -induced NGF-differentiated PC12 cells. We examined the effects of LXW7, CeO 2 @PAA, and CeO 2 @PAA-LXW7 on the viability of primary hippocampal neurons and found that there was no significant difference under control conditions, but increased cellular viability was observed in the case of H 2 O 2 -induced injury. We used H 2 O 2 -induced NGF-differentiated PC12 cells as the classical injury model to investigate the neuroprotective effect of CeO 2 @PAA-LXW7. In this study, LXW7, CeO 2 @PAA, and CeO 2 @PAA-LXW7 inhibit H 2 O 2 -induced oxidative stress by reducing the production of reactive oxygen species (ROS) and regulating Bax/Bcl-2, cleaved caspase-3 and mitochondrial cytochrome C (cyto C) in the apoptotic signaling pathways. We found that the levels of phosphorylation of focal adhesion kinase (FAK) and of signal transducer and activator of transcription 3 (STAT3) increased significantly in H 2 O 2 -induced NGF-differentiated PC12 cells, whereas LXW7, CeO 2 @PAA, and CeO 2 @PAA-LXW7 suppressed the increase to different degrees. Among the abovementioned changes, the inhibitory effect of CeO 2 @PAA-LXW7 on H 2 O 2 -induced changes, including the increases in the levels of p-FAK and p-STAT3, is more obvious than that of LXW7 or CeO 2 @PAA alone. In summary, these results suggest that integrin signaling participates in the regulation of apoptosis via the regulation of ROS and of the apoptosis pathway in H 2 O 2 -induced NGF-differentiated PC12 cells. LXW7, CeO 2 @PAA, and CeO 2 @PAA-LXW7 can play neuroprotective roles by counteracting the oxidative stress and apoptosis induced by H 2 O 2 in NGF-differentiated PC12 cells. CeO 2 @PAA-LXW7 exerting a more powerful synergistic effect via the conjunction of LXW7 and CeO 2 @PAA.
研究领域:
神经科学
·
药理学
·
细胞生物学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Therapeutics
·
2024
·Vol. 7
·期 8
·2400045
·
IF 3.7
Shanshan Wang,Zhiqiang Bi,Tianming Lu,Ruoning Qian,Jie Yu,Qiang Zhang,Hao Yang,Wenli Lu,Yuanyuan Guo,Xiaoqing Xin,Yong Bian,Ruogu Qi
Colorectal cancer (CRC) stands out as one of the most prevalent gastrointestinal cancers. Current treatment strategies for CRC are significantly hindered by systemic toxicity and suboptimal therapeutic efficacy. This study aims to overcome these limitations by developing a robust tumor-targeting chemo-photothermal strategy, combining Bortezomib (BTZ) as a proteasome inhibitor, IR780 iodide as a near-infrared dye, and Photothermal Therapy (PTT) agent, with hyaluronic acid (HA) serving as the shell for tumor targeting, denoted as HA/PB@IR780. The investigations reveal the impressive tumor-targeting affinity of HA/PB@IR780, leading to a synergistic chemo-photothermal therapeutic effect both in vitro and in vivo. Additionally, this material demonstrates the capability for drug release triggered by low pH conditions. Moreover, HA/PB@IR780 induced the generation of reactive oxygen species (ROS), triggered cells apoptosis via the PERK-CHOP-Bcl-2 pathway, and induced Immunogenic Cell Death (ICD) in CT26 cells. Importantly, HA/PB@IR780 selectively targets tumor sites, mitigating systemic toxic side effects and significantly extending the survival of CT26 tumor-bearing mice. In conclusion, this designed tumor-targeting nanocarrier represents a promising and potentially effective platform for the precise treatment of CRC.
研究领域:
肿瘤学
·
纳米技术
·
药理学
·
细胞生物学
·
治疗学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
·
IF 5.3
Xixi Chen,Fang Li,Binghui Cui,Qingyi Yan,Caisheng Qiu,Zengyan Zhu,Lijuan Wen,Weiliang Chen
It has been reported that proteolysis-targeting chimeras (PROTACs) can effectively degrade intracellular oncogenic proteins, providing an ideal strategy for cancer treatment. ARV825, a bromodomain-containing protein 4 (BRD4)-PROTAC, has demonstrated the capacity to enhance the antitumor effect of the classic chemotherapeutic agent docetaxel (DTX). However, there are three major challenges to the broader in vivo application of ARV825: poor solubility, poor permeability, and off-target effects. Additionally, the efficient co-delivery of ARV825 and DTX to tumor tissues for a synergistic therapeutic effect remains unresolved. In this study, liposomes were utilized as co-delivery vehicles for ARV825 and DTX to effectively address these issues. The well-established liposomes significantly improved the solubility of both ARV825 and DTX while maintaining a sustained release profile in blood-mimetic conditions. The co-loaded liposomes accumulated in tumor tissues via the enhanced permeability and retention (EPR) effect. After internalization, ARV825 effectively degraded intracellular BRD4 proteins and downregulated the expression of both Bcl-2 and PD-L1 proteins, thereby increasing tumor cell apoptosis and enhancing the tumor immune response. This, in turn, augmented the antitumor effect of DTX in vivo without undesired side effects. In conclusion, BRD4-PROTAC may serve as a promising synergistic agent alongside the conventional chemotherapeutic agent DTX, with liposomes functioning as effective co-delivery vehicles.
研究领域:
肿瘤学
·
药学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2017
·
IF 2.759
Yanyan Zhu,Yameng Jiang,Lei Shi,Linying Du,Xiaodong Xu,Enxia Wang,Yong Sun,Xin Guo,Boyang Zou,Huaxin Wang,Changyuan Wang,Lidan Sun,Yuhong Zhen
7- O -Geranylquercetin (GQ) is a novel O -alkylated derivate of quercetin . In this study, we evaluated its apoptosis induction effects in human gastric cancer cell lines SGC-7901 and MGC-803 and explored the potential molecular mechanisms. The results demonstrated that GQ lowered viability of SGC-7901 and MGC-803 cells in a dose- and time-dependent manner without apparent cytotoxicity to human gastric epithelial cell line GES-1. GQ could induce apoptosis in SGC-7901 and MGC-803cells, and arrest the gastric cancer cells at G2/M phase. Mechanism study showed that GQ triggered generation of reactive oxygen species (ROS), then activated p38 and JNK signaling pathways , subsequently led to mitochondrial impairment by regulating the expression of Bcl-2, Bcl-xl and Bax, and finally promoted the release of cytochrome c and the activation of caspases to induce apoptosis. In addition, Z-VAD-FMK (caspase inhibitor) could reverse GQ-induced apoptosis. SB203580 (p38 inhibitor) and SP600125 (JNK inhibitor) could rescue GQ-induced cell death and attenuate mitochondrial signal pathway activation. Furthermore, NAC (ROS inhibitor) could rescue GQ-induced cell death, reduce ROS generation, decrease the phosphorylation of p38 and JNK, and then attenuate the activation of mitochondrial signal pathway. Taken together, GQ induces caspase-dependent apoptosis in gastric cancer cells through activating ROS-MAPK mediated mitochondrial signal pathway. This study highlights the potential use of GQ as a gastric cancer therapeutic agent.
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
CELL BIOCHEMISTRY AND BIOPHYSICS
·
2014
·Vol. 71
·期 3
·1349-1356
·
IF 2.38
Jin Di,Cao Ming,Mu Xin,Yang Guoliang,Xue Wei,Huang Yiran,Chen Haige
Catalpol is an iridoid glucoside extracted from the traditional Chinese medicinal plant called Rehmannia glutinosa , and it is reported to possess a variety of pharmacological activities. The goal of this research was to explore the effect of catalpol on the human bladder cancer cells T24. The cells were treated for different durations with various concentrations of catalpol. Then the viability, mobility, and invasiveness of the cells were determined by MTT assay and flow cytometry, respectively. Catalpol was found to significantly suppress the proliferation, migration, and invasiveness of T24 bladder cancer cells in a dose- and time-dependent manner. The results also revealed that catalpol promoted apoptosis and caused the cell-cycle arrest at G2/M phase. Furthermore, the catalpol-mediated apoptosis was found to involve the modulation of PI3K/Akt pathway and inhibit the expression of anti-apoptotic B cell lymphoma-2 (Bcl-2) family proteins. Also, the expressions of Bcl-2 proapoptotic effectors, Bcl-2-associated X protein, and Bcl-2 associated death promoter were up-regulated in the cells treated with catalpol. The enzymes involved in the ultimate process of apoptosis, active caspase-3 and poly ADP ribose polymerase were elevated, and the latter was observed to be cleaved, indicating that catalpol-accelerated cell apoptosis involved a caspase-dependent pathway. These results suggest that catalpol might serve to be a promising therapeutic agent for the treatment of human bladder cancer.
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
危险品化学品经营许可证（带存储）