Frontiers in Chemistry
·
2022
·
IF 5.545
Zhu Jun,Kong Ling-Qi,Chen Qin-Hua,Li Bin,Wu Lun,Ran Feng-Ying,Ke Li-Na,Zeng Xiao-Hua,Wang Hong-Mei
Marine alkaloids have novel structures and antitumor activities. Therefore, we synthesized rhopaladins’ analogs from marine alkaloids rhopaladins A-D and modified their structures to synthesize 4-benzylidene-5-pyrrolidone derivatives. Among the compounds, (2E, 4E)-4-(4-chlorobenzylidene)-2-(4-chlorostyryl)-N-cyclohexyl-1-(4-fluorophenyl)-5-oxopyrrolidine-2-carboxamide (RPDPRH) has high efficiency and less hepatotoxicity, with IC50 values of 4.66, 6.42, 17.66, 15.2, 12.36, 22.4, and 243.2 μM in vitro anti-proliferative activity testing against cervical cancer C-33A, CaSki, SiHa, and HeLa cells, human hepatocarcinoma HepG2 and 7402 cells, and human normal liver LO2 cells, respectively. In particular, RPDPRH has similar activity to cisplatin on human hepatocarcinoma cells, and cisplatin served as a positive control in our study. Next, the apoptosis of HepG2 and 7402 cells induced by RPDPRH at different concentrations was detected by Annexin V/PI flow cytometry. Moreover, the expression of apoptotic proteins was detected by Western blot analysis. Finally, the results showed that RPDPRH could induce apoptosis of hepatocarcinoma cells by regulating Bax and Bcl-2 expressions. In summary, our results indicate that RPDPRH has the potential to serve as an antitumor agent and plays a significant role in future studies.
研究领域:
药理学
·
肿瘤学
·
药物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Chuang Yang,Zheng Chen,Min Wei,Shen Hu,Mengyuan Cai,Nan Wang,Yunan Guan,Fangyuan Li,Qiang Ding,Daishun Ling
Ferroptosis has recently become an attractive strategy to combat the chemoresistance of cancer cells, but the intracellular ferroptosis defense system greatly challenges the efficient ferroptosis induction. Herein, we report a ferrous metal-organic framework-based nanoagent (FMN) that inhibits the intracellular upstream glutathione synthesis and induces self-amplified ferroptosis of cancer cells, for reversing chemoresistance and boosting chemotherapy. The FMN is loaded with SLC7A11 siRNA (siSLC7A11) and chemotherapeutic doxorubicin (DOX), which shows enhanced tumor cell uptake and retention, thus ensuring the effective DOX delivery and tumor intracellular iron accumulation. Importantly, the FMN simultaneously catalyzes the iron-dependent Fenton reaction and triggers the siSLC7A11-mediated suppression of upstream glutathione synthesis for intracellularly self-amplified ferroptosis, which further inhibits P-glycoprotein activity for DOX retention, and regulates the expression of Bcl-2/Bax to reverse the apoptotic resistance state of tumor cells. The FMN-mediated ferroptosis is also demonstrated in ex vivo patient-derived tumor fragment platform. Consequently, FMN successfully reverses cancer chemoresistance and achieves a highly efficient in vivo therapeutic efficacy in MCF7/ADR tumor-bearing mice. Our study provides a self-amplified ferroptosis strategy via inhibiting intracellular upstream glutathione synthesis, which is effective to reverse cancer chemoresistance.
研究领域:
肿瘤学
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纳米技术
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Arabian Journal of Chemistry
·
2022
·
IF 6.212
Zizhen Zhao,Chen Fu,Yuping Zhang,Yingying Zhang,Xiaoxi Yang,Ailing Fu
The incidence of HCC continues to increase rapidly in recent years. the principle of developing anti-HCC drugs is to specifically kill tumor cells, without affecting the function of normal cells. Here we synthesized a novel protonic compound bis(5-amino-1,10-phenanthroline) (P-BAP), and the antitumor activity was explored in vitro and in vivo . The results showed that P-BAP could selectively inhibit the proliferation of tumor cells, and induce HCC apoptosis. In HCC-bearing mice, P-BAP could effectively retard the tumor growth, even completely eliminate the tumors at the dose of 5 mg/kg, and meanwhile P-BAP had no significant effect on mouse body weight. Mechanism analysis revealed that P-BAP could down-regulate the protein expressions of pleomorphic adenoma gene like-2 (PLAGL2), HIF-1α and β-catenin, and up-regulate the levels of pro-apoptotic protein BAX and BNIP3. In addition, P-BAP could reduce mitochondrial respiratory chain complex activities, leading to insufficient ATP production. The study provides a new approach for designing selective antitumor drugs, and suggests that P-BAP would be a potential candidate for HCC therapy.
研究领域:
肿瘤学
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药理学
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分子生物学
✓ 已验证
DOI
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2024
·
IF 4
Wei Tian,Mingyu Ji,Tingting Yang,Wen Zhong,Yanping Li,Mei Yang,Peilin Yang,Xing Long
Two new rhein-organotin complexes Ph 3 Sn(O 2 CC 14 H 7 O 4 ) ( RS01 ) and Cy 3 Sn(O 2 CC 14 H 7 O 4 ) ( RS02 ) were synthesized and characterized by elemental analysis, IR, 1 H NMR, 13 C NMR, 119 Sn NMR, X-ray crystallography and thermo-gravimetric analysis. Both complexes has a triclinic crystal system P -1 space group and one-dimensional supramolecular chain structure. The MTT results demonstrated that rhein's anticancer activity was effectively increased by introducing organotin, RS01 and RS02 exhibited excellent anticancer activity in vitro, significantly superior to cisplatin and mitoxantrone. Interestingly, despite the fact that RS01 and mitoxantrone share the same 9,10-anthraquinone scaffold structure, RS01 not only showed high anticancer activity but also much lower nephrotoxicity than mitoxantrone. Flow cytometry showed that RS01 could significantly induce cell apoptosis and arrest cell cycle in G2 phase. Molecular docking and UV–Vis absorption spectra suggested that RS01 may be intercalation with DNA. Furthermore, western blot results showed that RS01 activated the DNA damage critical protein γ -H 2 AX and regulated the expression level of the mitochondrial apoptotic pathway critical protein (Bax/Bcl-2). Thus, RS01 induced cell death may be mediated through DNA damage and mitochondrial pathways. As a result, RS01 has significant development and application potential as an anticancer agent.
研究领域:
无机化学
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金属有机化学
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癌症研究
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药学
✓ 已验证
DOI
高影响因子
FOOD CHEMISTRY
·
2024
·
IF 8.5
Mingyi Zhang,Ting Chen,Jiaruo Hu,Weidong Zhang,Mingyue Shen,Qiang Yu,Yi Chen,Jianhua Xie
Premature ovarian failure (POF) is a common female reproductive disorder, with oxidative damage playing a significant role in its development. Studies had demonstrated the beneficial antioxidant, anti-aging, and other biological properties of swim bladder collagen (peptide). In this study, acid extraction, water extraction, and enzymatic hydrolysis methods were used to extract collagen (peptide) from sturgeon ( Acipenser sinensis ) swim bladder, all of which exhibited significant antioxidant activity. Moreover, the effects observed in POF mice were enhanced, including an increasing in the number of growing ovarian follicles, regulation of serum hormone levels, and alterations in signaling pathways, as evidenced by the up-regulation of Phosphatidylinositol 3-kinase/Protein Kinase B (PI3K/Akt) and B cell lymphoma-2/ Bcl-associated x protein (Bcl-2/Bax) pathways, alongside the down-regulation of the mitogen-activated protein kinases (MAPK) signaling pathway. Sturgeon swim bladder collagen (peptide) could protect against cyclophosphamide-induced POF in mice, which could be very beneficial in the future advancement of health products.
研究领域:
生殖生物学
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药理学
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生物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
·
2024
·
IF 4.1
Qiulu Li,Kaixin Ping,Yannan Xiang,Ying Sun,Zunhan Hu,Shujuan Liu,Xinying Guan,Mian Fu
Avamectin (AVM), a macrolide antibiotic, is widely used in fisheries, agriculture, and animal husbandry, however, its irrational use poses a great danger to aquatic organisms. Ferulic acid (FA) is a natural chemical found in the cell walls of plants. It absorbs free radicals from the surrounding environment and acts as an antioxidant. However, the protective effect of FA against kidney injury caused by AVM has not been demonstrated. In this study, 60 carp were divided into the control group, AVM group (2.404 μg/L), FA+AVM group and FA group (400 mg/kg). Pathological examination, quantitative real-time PCR (qPCR), reactive oxygen species (ROS) and western blot were used to evaluate the preventive effect of FA on renal tissue injury after AVM exposure. Histological findings indicated that FA significantly reduced the swelling and infiltration of inflammatory cells in the kidney tissues of carp triggered by AVM. Dihydroethidium (DHE) fluorescent probe assay showed that FA inhibited the accumulation of kidney ROS. Biochemical results showed that FA significantly increased glutathione (GSH) content, total antioxidant capacity (T-AOC) and catalase (CAT) activity, and decreased intracellular malondialdehyde (MDA) content. In addition, western blot results revealed that the protein expression levels of Nrf2 and p-NF-κBp65 in the carp kidney were inhibited by AVM, but reversed by the FA. The qPCR results exhibited that FA significantly increased the mRNA levels of tgf-β1 and il-10 , while significantly down-regulated the gene expression levels of tnf-α , il-6 and il-1β . These data suggest that FA can reduce oxidative stress and renal tissue inflammation induced by AVM. At the same time, FA inhibited the apoptosis of renal cells induced by AVM by decreasing the transcription level and protein expression level of Bax, and increasing the transcription level and protein expression level of Bcl2, PI3K and AKT. This study provides preliminary evidence for the theory that FA reduces the level of oxidative stress, inflammation response and kidney tissue damage caused by apoptosis in carp, providing a theoretical basis for the prevention and treatment of the AVM.
研究领域:
水生毒理学
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药理学
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生物化学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2023
·
IF 4.3
Guoliang Chen,Juan Liu,Huiyun Wang,Mingxing Wang,Guixue Wang,Tingzhang Hu
SYP-3343 is a novel strobilurin fungicide with excellent and broad-spectrum antifungal activity , and its potential toxicity raises public health concerns. However, the vascular toxicity of SYP-3343 to zebrafish embryos is still not well understood. In the present study, we investigated the effects of SYP-3343 on vascular growth and its potential mechanism of action. SYP-3343 inhibited zebrafish endothelial cell (zEC) migration, altered nuclear morphology, and triggered abnormal vasculogenesis and zEC sprouting angiogenesis , resulting in angiodysplasia . RNA sequencing showed that SYP-3343 exposure altered the transcriptional levels of vascular development-related biological processes in zebrafish embryos including angiogenesis, sprouting angiogenesis, blood vessel morphogenesis , blood vessel development, and vasculature development. Whereas, the addition of NAC exerted an improvement effect on zebrafish vascular defects owing to SYP-3343 exposure. Additionally, SYP-3343 altered cell cytoskeleton and morphology, obstructed migration and viability, disrupted cell cycle progression, and depolarized mitochondrial membrane potential, as well as promoted apoptosis and reactive oxygen species (ROS) in HUVEC. SYP-3343 also caused an imbalance of the oxidation and antioxidant systems and irritated the alterations in the cell cycle- and apoptosis-related genes in HUVECs. Collectively, SYP-3343 has high cytotoxicity, possibly by up-regulating p53 and caspase3 expressions and bax/bcl-2 ratio via ROS, leading to malformed vascular development.
研究领域:
毒理学
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发育生物学
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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
Biomolecules & Therapeutics
·
2023
·
IF 3.7
Nayun Kim,Junhye Kwon,Ui Sup Shin,Joohee Jung
Colorectal cancer (CRC) is one of the most high-risk cancers; however, it has been suggested that estrogen signaling in CRC could have a protective effect. Therefore, we focused on the function of the G protein-coupled estrogen receptor (GPER) among the estrogen receptors in CRC. In this study, we investigated the therapeutic effect of resveratrol via GPER in CRC (RKO and WiDr) cells, CRC cell-derived xenograft models, and organoids (30T and 33T). Resveratrol significantly suppressed cell viability and proliferation in highly GPER-expressing RKO cells compared to that in low GPER-expressing WiDr cells. In xenograft models, resveratrol also delayed tumor growth and exhibited a high survival rate depending on GPER expression in RKO-derived tumors. Furthermore, resveratrol significantly inhibited the viability of organoids with high GPER expression. Additionally, the anticancer effect of resveratrol on CRC showed that resveratrol rapidly responded to GPER, while increasing the expression of p-ERK and Bax and cleaving PARP proteins.
研究领域:
肿瘤学
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分子生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2017
·
IF 3.649
Ting Yue,He-Lin Xu,Pian-Pian Chen,Lei Zheng,Qun Huang,Wen-Shuang Sheng,Yuan-Di Zhuang,Li-Zhuo Jiao,Ting-Ting Chi,De-Li ZhuGe,Jin-Jin Liu,Ying-Zheng Zhao,Li Lan
Diabetic nephropathy (DN) is one of the most common and lethal microvascular complications of diabetes. This study aimed to explore whether coenzymeQ10 (CoQ10) as an antioxidant combined with ultrasound-targeted microbubble destruction (UTMD) could reverse the progress of early diabetic nephropathy (DN). CoQ10 has great potential to treat early DN. However, the clinical application of CoQ10 has been limited because of its low aqueous solubility and non-specific distribution. Therefore, CoQ10-loaded liposomes (CoQ10-lip) were prepared and combined with ultrasound microbubbles for the early theranostics of DN. CoQ10-lip exhibited a good round morphology with a diameter of 183 ± 1.7 nm and a negative zeta potential of −25.3 mV, which was capable of prolonging the release of the encapsulated CoQ10. The early DN rat models were induced by streptozotocin (STZ) and confirmed by contrast-enhanced ultrasound (CEUS) and 24-h urinary albumin. After the administration of CoQ10-lip combined with the UTMD technique to rats with early DN, the morphology and function of the kidney were evaluated by ultrasonography, histological and molecular analyses. The renal hemodynamics were significantly improved, moreover, 24-h urinary protein, and oxidative stress indexes were modulated after treatment with CoQ10-lip + UTMD indicating recovery of renal function. An elevated level of Nphs2 protein and reduced caspase 3 level indicated the preservation of podocytes and inhibition of cell apoptosis after CoQ10-lip + UTMD treatment. The molecular mechanism was associated with the upregulation of Bcl-2 and the downregulation of Bax. Moreover, the combination of CoQ10-lip and ultrasound microbubbles demonstrated a better protective effect on the damaged kidney than the other groups (free CoQ10 or CoQ10-lip+/− UTMD). Conclusively, CoQ10-lip in combination with ultrasound microbubbles might be a potential strategy to reverse the progress of early DN.
研究领域:
药理学
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生物医学工程
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肾病学
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产品关联
DOI
PubMed
高影响因子
BIOLOGICAL TRACE ELEMENT RESEARCH
·
2017
·Vol. 181
·期 1
·62-70
·
IF 2.399
Zhang Hui,Chang Zhenyu,Mehmood Khalid,Abbas Rao Zahid,Nabi Fazul,Rehman Mujeeb Ur,Wu Xiaoxing,Tian Xinxin,Yuan Xiaodan,Li Zhaoyang,Zhou Donghai
Nano-sized copper particles are widely used in various chemical, physical, and biological fields. However, earlier studies have shown that nano copper particles (40–100 μg/mL) can induce cell toxicity and apoptosis. Therefore, this study was conducted to investigate the role of nano copper in mitochondrion-mediated apoptosis in PK-15 cells. The cells were treated with different doses of nano copper (20, 40, 60, and 80 μg/mL) to determine the effects of apoptosis using acridine orange/ethidium bromide (AO/EB) fluorescence staining and a flow cytometry assay. The levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in the PK-15 cells were examined using commercially available kits. Moreover, the mRNA levels of the Bax, Bid, Caspase-3, and CYCS genes were assessed by real-time PCR. The results revealed that nano copper exposure induced apoptosis and changed the mitochondrial membrane potential. In addition, nano copper significantly altered the levels of the Bax, Bid, Caspase-3, and CYCS genes at a concentration of 40 μg/mL. To summarize, nano copper significantly ( P < 0.05) decreased the level of SOD and increased the level of MDA in PK-15 cells. Altogether, these results suggest that nano copper can play an important role in inducing the apoptotic pathway in PK-15 cells, which may be the mechanism by which nano copper induces nephrotoxicity.
研究领域:
细胞生物学
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毒理学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ALZHEIMERS DISEASE
·
2016
·Vol. 50
·期 4
·1149-1162
·
IF 3.92
Zhu Mingming,Huang Cong,Ma Xiao,Wu Rui,Zhu Weiwei,Li Xiaoting,Liang Zhaofeng,Deng Feifei,Zhu Jianyun,Xie Wei,Yang Xue,Jiang Ye,Wang Shijia,Wu Jieshu,Geng Shanshan,Xie Chunfeng,Zhong Caiyun
Neuronal cell death is an important feature of neurodegeneration. Aluminum is associated with neurodegenerative disorders, particularly Alzheimer’s disease. However, the underlying mechanisms by which aluminum induces neuronal apoptosis remain to be elucidated. miR-19 is a key miRNA implicated in regulating cell survival process, while the role of miR-19 in Alzheimer’s disease has not been investigated. In the present study, we showed that Aluminum maltolate (Al-malt), a lipophilic Al complex which is a common component of human diet with the ability to facilitate the entry of Al into the brain, induced apoptosis in human neuroblastoma SH-SY5Y cells, along with downregulation of miR-19a/miR-19b, upregulation of miR-19-targeted PTEN, and alterations of its downstream apoptosis related proteins including AKT, p53, Bax, and Bcl-2. miR-19 overexpression attenuated Al-malt-induced apoptosis as well as changes in the expression of apoptosis related proteins in SH-SY5Y cells. We further revealed that exposure of rats to Al-malt for 12 weeks at doses relevant to human exposure significantly elevated Al concentrations in serum and brain tissues. Al-malt dose-dependently induced apoptosis in rat brain, as evidenced by increased caspase activation and increased TUNEL staining. Consistent with in vitro results, Al-malt reduced miR-19 expression and altered the expression of apoptotic related proteins in rat brain. Taken together, our data suggest for the first time that miR-19 modulation is critically involved in Al-induced neural cell apoptosis. Findings from this study could provide new insight into the molecular mechanisms of Al-associated neurodegenerative pathogenesis.
研究领域:
神经科学
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分子生物学
·
毒理学
·
神经退行性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LIFE SCIENCES
·
2022
·
IF 6.78
Lei Wang,Jiahui Ma,Wei Wu,Yimeng Fang,Fan Liu,Qinsi Yang,Xiang Hu,Xuejiang Gu,Zhiying He,Da Sun,Libo Jin,Xingxing Zhang
Background Depression is the most known complication of type 2 diabetes mellitus (T2DM). Aerobic exercise improves glycemic control in T2DM, although the underlying mechanisms of comorbid depression-like behaviors in T2DM have not yet been fully elucidated. Methods 120 zebrafish were randomly assigned to four groups: Control, T2DM, T2DM + metformin, and T2DM + aerobic exercise. Then, all animals except the control group were fed with high glucose fairy shrimp (~40 g/kg/day) and exposed reserpine (40 μg/ml for 20 min) for 10 days. Here, behavioral tests were used for model verification. Following the verification, all groups were treated as before. Additionally, the T2DM + metformin group received metformin (~10.6 mg/kg/day) at the same time, while the T2DM + aerobic exercise group received aerobic exercise 30 min/day. Finally, blood glucose and behavioral tests, as well as protein and molecular levels were determined at Day 11 and 12. Results Aerobic exercise alleviated depressive-like behavior and enhanced the levels of antidepressant biomarkers (NE, 5-HIAA) in zebrafish after 10 consecutive days of exercise. Additionally, 10 consecutive days of aerobic exercise decreased the levels of inflammatory biomarkers (IFN-γ, IL-1, IL-4) and depressive biomarkers (cortisol). Meanwhile, it also aided in the reduction of CD11b, IL-6, IL-6R, and caspase-3 expression to combat the neuroinflammation induced by T2DM, mediated the BDNF-TrkB pathway, and increased Bcl-2/Bax levels. Conclusion Given the remarkable similarity in neurochemistry between humans and zebrafish, this study supports the effectiveness of aerobic exercise as clinical guidance in preventing and treating T2DM complicated with depression.
研究领域:
内分泌学
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神经科学
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药理学
·
运动科学
✓ 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）