MICROCHEMICAL JOURNAL
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2024
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IF 4.9
Di Wu,Lingxia Qin,Yeping Cen,Jin Lu,Shaohua Ma,Yufang Hu
The necessity for precise delineation and quantitation of pyrophosphatase (PPase) activities is underscored, especially in aggressive prostate cancer, driving the demand for more refined analytical techniques due to challenges associated with inadequate sensitivity and poor signal amplification. In response, a novel electrochemical method utilizing in-situ copper(II) (Cu(II))-based Fast Scan Cyclic Voltammetry (FSCV) is introduced for the advanced detection of PPase in LNCaP prostate cancer cells. This technique is characterized by the exploitation of competitive binding between Cu(II) and L-Phenylalanine (L-Phe) versus pyrophosphate (PPi), with FSCV technology enhanced by ohmic drop compensation to improve detection sensitivity and signal reliability. Through the application of the FSCV technique transitioned to Current(I)-Voltage(V) analysis, the signal generation is facilitated by an L-Phe-Cu(II) complex, driven by the redox reaction of in-situ Cu(II), specifically its rapid transition from the Cu(0) state back to the Cu(II) state. When this complex is anchored onto a gold substrate modified with cucurbit[7]uril (CB[7]) through supramolecular host–guest interactions, a significant FSCV signal is elicited. A detection limit of 0.05 mU/mL (S/N = 3) is subsequently achieved when the method is applied to the quantification of PPase concentration. Leveraging the FSCV method, we have effectively analyzed PPase activity in LNCaP cells, offering a fresh perspective on tumor marker analysis and fostering advancements in drug development.
研究领域:
生物化学
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医学诊断
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癌症研究
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产品关联
DOI
高影响因子
Cancer Cell International
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2019
·Vol. 19
·期 1
·1-10
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IF 3.439
Han Jingli,Zhang Junhua,Zhang Wei,Zhang Dalei,Li Ying,Zhang Jinsong,Zhang Yaqun,Diao Tongxiang,Cui Luwei,Li Wenqing,Xiao Fei,Liu Ming,Zou Lihui
Background Abiraterone and MDV3100 are two effective anticancer agents for prostate cancer, however, the mechanism of their downstream action remains undefined.Methods A dual fluorescent biosensor plasmid was transfected in LNCaP cells to measure mitophagy. The DNA of LNCaP cells was extracted and performed with quantitative real-time PCR to detect mitochondrial DNA copy number. JC-1 staining was utilized to detect the mitochondrial membrane potential and electron microscope was performed to analyze mitochondrial morphology. Moreover, the protein levels of mitochondrial markers and apoptotic markers were detected by western blot. At last, the proliferation and apoptosis of LNCaP cells were analyzed with CCK-8 assay and flow cytometry after abiraterone or MDV3100 treatment.Results Mitophagy was induced by abiraterone and MDV3100 in LNCaP cells. The low expression level of mitochondrial DNA copy number and mitochondrial depolarization were further identified in the abiraterone or MDV3100 treatment groups compared with the control group. Besides, severe mitochondria swelling and substantial autophagy-lysosomes were observed in abiraterone- and MDV3100-treated LNCaP cells. The expression of mitochondria-related proteins, frataxin, ACO2 and Tom20 were significantly downregulated in abiraterone and MDV3100 treated LNCaP cells, whereas the expression level of inner membrane protein of mitochondria (Tim23) was significantly upregulated in the same condition. Moreover, the proliferation of LNCaP cells were drastically inhibited, and the apoptosis of LNCaP cells was increased in abiraterone or MDV3100 treatment groups. Meanwhile, the addition of mitophagy inhibitor Mdivi-1 (mitochondrial division inhibitor 1) could conversely elevate proliferation and constrain apoptosis of LNCaP cells.Conclusion sOur results prove that both abiraterone and MDV3100 inhibit the proliferation, promote the apoptosis of prostate cancer cells through regulating mitophagy. The promotion of mitophagy might enhance the efficacy of abiraterone and MDV3100, which could be a potential strategy to improve chemotherapy with these two reagents.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
Medicina-Lithuania
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2018
·Vol. 54
·期 3
·39
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IF 1.429
Wei Li,Bi-De Liu,Kai Liao,Yong Liu,Zi-Jin Wan,Yu-Fen Dong,Qian-Qian Cao,Qian Zhu,Xiao Gu
Background and Objective:Although triptolide was effective for prostate cancer (PCa), the mechanism is still unclear. Androgen receptor (AR) plays a large role in the development and progression of PCa, even after castration. The present study aimed at investigating the effects of triptolide on AR protein stability and the possible mechanism.Materials and Methods:By blocking protein synthesis with cycloheximide (CHX), the effect of triptolide on AR protein stability was investigated with western blot assay. The potential role of calpains in triptolide reduced AR protein stability was investigated with calpain inhibitor and Ca2+chelator.Results:Triptolide down-regulated AR protein level when protein synthesis was blocked by CHX, demonstrating the decrease of AR protein stability. The AR protein level was restored when the cells were co-treated with triptolide and calpain inhibitor or Ca2+chelator, indicating the important role of calpains.Conclusions:The results indicate that triptolide can activate calpain via promoting intracellular Ca2+accumulation, and thus decrease the stability of AR protein, subsequently resulting in the breakdown of the AR protein in LNCaP cells. This work provides an experimental basis and evidence to elucidate the anti-PCa mechanisms of triptolide.Keywords:triptolide;androgen receptor;calpain;protein stability
研究领域:
肿瘤学
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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
ACS Applied Materials & Interfaces
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2024
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IF 8.3
Xueyi Liu,Pei Zhang,Huijia Song,Xiaoshuang Tang,Yi Hao,Yibing Guan,Tie Chong,Sameer Hussain,Ruixia Gao
Prostate cancer is the most common malignancy diagnosed in men. Androgens are directly related to its pathogenesis. Inhibition of the androgen receptor (AR) is considered to be the most promising therapeutic approach for the treatment of prostate cancer. In this study, a new type of pH-responsive dual androgen-blocking nanodrug (FASC MIPs) based on a molecularly imprinted polymer has been designed and synthesized. The nanodrug could selectively sequester testosterone from the prostate tumor through specific molecular imprinting sites and simultaneously deliver the AR inhibitory drug bicalutamide, which ultimately leads to enhanced synergistic therapy of prostate cancer. FASC MIPs demonstrate excellent pH responsiveness in a simulated tumor microenvironment due to the presence of chitosan and significantly inhibit the growth of prostate cancer cells (LNCaP cells) by blocking the G1 phase of cytokinesis. Additionally, the nanodrug also displayed excellent antitumor properties in a xenograft mouse model of prostate cancer without any sign of detrimental effects on healthy tissues and organs. Both in vitro and in vivo studies verified the augmented and synergistic therapeutic effects of FASC MIPs, and the proposed dual-androgen-blocking strategy could explore novel avenues in prostate cancer treatment.
研究领域:
肿瘤学
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药学
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纳米技术
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
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2023
·
IF 8.8
Mingzhao Li,Ren Wang,Pan Wang
Endocrine disruptors are environmental chemicals that can interfere with the endocrine system. However, research on endocrine disruptors that interfere with androgen's actions is still limited. The purpose of this study is to use in silico computation, i.e. , molecular docking to facilitate the identification of environmental androgens. Computational docking was used to study the binding interactions of environmental/industrial compounds with the three dimensional structure of human androgen receptor (AR). Then reporter assay and cell proliferation assay using AR-expressing LNCaP prostate cancer cells were used to determine their in vitro androgenic activity. Animal studies using immature male rats were also carried out to test their in vivo androgenic activity. Two novel environmental androgens were identified. As a photoinitiator, 2-benzyl-2-(dimethylamino)-4′-morpholinobutyrophenone (Irgacure 369, abbreviated as IC-369) is widely used in the packaging and electronics industries. Galaxolide (HHCB) is widely used in the production of perfume, fabric softeners and detergents. We found that both IC-369 and HHCB could activate AR transcriptional activity and promote cell proliferation in AR-sensitive LNCaP cells. Furthermore, IC-369 and HHCB could induce cell proliferation and histological changes of seminal vesicles in immature rats. RNA sequencing and qPCR analysis showed that androgen-related genes in seminal vesicle tissue were up-regulated by IC-369 and HHCB. In conclusion, IC-369 and HHCB are new environmental androgens that bind AR and induce AR transcriptional activity, thereby exerting toxicological effects on the development of male reproductive organs.
研究领域:
环境科学
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毒理学
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分子生物学
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内分泌学
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2021
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IF 4.539
Chang-Ming Liu,Guang-Bing Chen,Li-Heng Lin,Jia-Bin Zhang,Shan-Ming Guo,Ming-Xiong Sheng
Prostate cancer is one of most devastating disease with the poor prognosis in men. The efficacy of conventional therapies is far from satisfactory due to the insufficient chemotherapeutic delivery to the cancer cells which requires the extremely high or toxic dose to reach the therapeutic window. In this work, a charge reversal nanoplatform based on mesoporous silica nanoparticle (MSN) with a core-shell structure is developed to programmatically overcome persistent obstacles in drug delivery to prostate cancer. MSN is served as a container to high-efficiently pack chemotherapeutic drug of triptolide . 2, 3-dimethylmaleic anhydride grafted poly-(allylamine hydrochloride) (PAH-DA) is used as the out shell with a negative charge for pH-triggered charge reversal, which can facilitate the cellular uptake. Furthermore, PAH-DA shell can also act as pH-sensitive gatekeepers while will elegantly shed from MSN under acidic tumor microenvironment for controlling drug release. As expected, in vitro cell experiments demonstrated that the as-prepared nanoplatform (denoted as MSN-T@PAH-DA) could be efficiently uptaken by LNCaP prostate cancer cells and exhibited a better anti-cancer effect at pH 6.5 as compared to that at pH 7.4. After intravenous injection, MSN-T@PAH-DA had a relatively higher tumor accumulation than MSN-T@PAH-SA counterpart without charge conversion ability, and thus achieving enhanced tumor growth suppression in mouse model of prostate cancer. Therefore, the pH-response surface charge reversal capacity of PAH-DA shell could enable multitasking in controlling drug release, regulating tumor accumulation and cellular internalization, which provided a promising strategy for efficient prostate tumor treatment.
研究领域:
纳米技术
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癌症研究
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药学
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生物材料
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药物递送系统
✓ 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）