ONCOLOGY REPORTS
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2018
·Vol. 39
·期 6
·3055-3063
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IF 2.976
Ailin Yang,Yanan Zhao,Ying Wang,Xiaojun Zha,Yunfang Zhao,Pengfei Tu,Zhongdong Hu
Prostate cancer is one of the most common malignancies occurring in males. Although large advances have been made in the pathogenesis of prostate cancer, the development of drugs with high efficacy and low toxicity for the treatment of prostate cancer is urgently needed. Recently, more and more attention has been paid to the antitumor effect of Traditional Chinese Medicine (TCM) worldwide. Trametes robiniophila Murr. (Huaier) has been applied as a type of TCM drug for ~1,600 years. Huaier exhibits excellent clinical efficacy in the treatment of cancer, including prostate cancer. However, the mechanisms underlying the anti-prostate cancer effect of Huaier remain largely unclear. In the present study, we revealed that Huaier aqueous extract inhibited the proliferative and metastatic capabilities of human prostate cancer PC3 cells through CCK-8 assay, in vitro scratch assay and Transwell assay. Moreover, decreased Lamin B1 was implicated in Huaier-induced suppression of proliferative and metastatic potential of PC3 cells. Intriguingly, we demonstrated that Huaier treatment induced autophagic cell death in PC3 cells. This study sheds new light on the mechanisms underlying the activity of Huaier against prostate cancer and provides a new theoretical basis for the clinical application of Huaier in prostate cancer.
研究领域:
肿瘤学
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中药学
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细胞生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICAL CHROMATOGRAPHY
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2019
·Vol. 33
·期 9
·e4555
·
IF 1.748
Ke-ke Cui,Yue-ting Cao,Jia-feng Shao,Zheng-yu Lu,Long-hu Wang
Bufadienolides are the main bioactive components of Venenum Bufonis (VB) and have been widely used to treat different types of human cancers for decades. The bufadienolide content in VB varies significantly in materials from different geographical origins. In this work, a new strategy for the quality assessment of VB was developed through quantitative analysis of multi-components by single marker (QAMS). Cinobufagin was selected as the internal reference substance; seven bufadienolides were separated and simultaneously determined based on relative correction factors. The correlation coefficient value ( r ≥ 0.9936) between QAMS and the normal external standard method proved the consistency of the two methods. According to the outcomes of 30 batches of VB samples, the contents of the seven bufadienolides were used for further chemometric analysis. All of the samples of VB from various geographical origins were divided into three categories based on hierarchical cluster analysis and radar plot, which indicated the crucial influence of geographical origins on VB. This study showed that QAMS combined with chemometristry could be used to comprehensively evaluate and effectively control the quality of VB from different geographical origins.
研究领域:
药理学
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分析化学
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中药学
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产品关联
DOI
PubMed
高影响因子
Heliyon
·
2024
·
IF 3.4
Qi Wu,Xue-li Ge,Zi-kai Geng,Hao Wu,Jing-yi Yang,Shi-rong Cao,Ai-lin Yang
HuaChanSu is active water extracts from the skin of Bufo bufo gargarizans Cantor. It has been already used to treat clinical cancers including HCC (Hepatocellular carcinoma, HCC), however, the molecular mechanisms under HuaChanSu's anti-cancer effects remain unclear. PPP (Pentose phosphate pathway, PPP), the major source of ribose and NADPH (Nicotinamide adenine dinucleotide phosphate, NADPH), is always over-activated and particularly critical for tumor cells growth. In this study, firstly, we illustrate that HuaChanSu restrains the growth of human hepatoma cells. More importantly, we demonstrate that the expression of G6PD (Glucose-6-phosphate dehydrogenase, G6PD), the first rate-limiting enzyme of the PPP, is restrained in human hepatoma cells after treatment with HuaChanSu. Additionally, our results show that G6PD enzyme activity and dimer formation are inhibited by HuaChanSu. Furthermore, we find that HuaChanSu could inhibit NADPH production and nucleotide level. In addition, we identify that expression of PLK1 (Polo-like kinase 1, PLK1) is also reduced in response to HuaChanSu, and knockdown of PLK1 restrains enzyme activity and dimer formation of G6PD, but has no effect on G6PD protein level. Subsequently, we demonstrate that inhibition of G6PD could restrain the proliferation of tumor cells and enhance the inhibitory effect of HuaChanSu on cell proliferation of human hepatoma cells. In conclusion, for the first time, our study reveals that HuaChanSu interferes with PPP via suppression of G6PD expression and enzyme activity to restrain growth of tumor cells, and these results provide a novel insight for the anti-hepatoma mechanisms of HuaChanSu and promote the innovation of the research model of TCM. Moreover, the development of drugs targeting abnormal tumor metabolism is currently a hot topic, our works provide theoretical support for further drug development from HuaChanSu, meanwhile, the revelation of the new molecular mechanism also provides a new perspective for the study of the pathogenesis of liver cancer.
研究领域:
肿瘤学
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药理学
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分子生物学
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癌症代谢
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产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
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2020
·
IF 3.594
Jinghui Zhang,Hongye Pan,Yang Chen,Zafar Iqbal Tanveer,Li Liu,Zongwei Cai,Yanjun Hong,Yongjiang Wu
Natural medicines are now gaining increasing acceptance around the global scope. Due to the complexity of composition , it is imperative to adopt a unique evaluation system, which is not confined to the content of finite marker compounds. This research presents the successful application of pharmacodynamics-based optimization to the ultrasound-assisted extraction of Chansu, a widely used natural medicine with complex bioactive ingredients. The effect of solvent concentration, solvent to solid ratio, extraction time and particle size, on two response indexes (extraction yield of total content of bufalin , cinobufagin and resibufogenin and anticancer activity) were evaluated by response surface methodology (RSM). Two models were built based on two response indexes, and both of them provided accurate predictions. Compared with extraction yield-based optimization, pharmacodynamics-based optimization aligns well with the integrity and complexity of natural medicines. Moreover, the pharmacodynamics-based optimization gives a more economical and efficient optimal condition, which is specifically embodied in the coarser requirement for particle size and the saving of extraction time and solvent. The recommended extraction conditions were methanol concentration of 83.54% (v/v), solvent to solid ratio of 26.23 mL/g, extraction time of 40.43 min and particle size of 61 mesh (0.212–0.25 mm). The present study elaborated the feasibility and implication of pharmacodynamics-based optimization, which provides useful information for further research on the extraction process of natural medicines.
研究领域:
药理学
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药物化学
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生物技术
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产品关联
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2018
·
IF 3.997
Xiao-jing Shi,Yan-yan Qiu,Hui Yu,Cheng Liu,Yu-xia Yuan,Pei-hao Yin,Tao Liu
A well-defined multifunctional brush-type polymeric prodrug covalently linked with an anticancer drug (bufalin, BUF), a tumor-targeting peptide (RGD), and an endosome-escaping polymer, poly( N,N -diethylaminoethyl methacrylate- co -butyl methacrylate (P(DEA- co -BMA)), was developed. Its anticancer performance against colon cancer was investigated in vitro and in vivo. Reversible addition-fragmentation transfer (RAFT) polymerization of oligo(ethylene glycol) monomethyl ether methacrylate (OEGMA), 2-((3-( tert -butoxy)-3-oxopropyl)thio)ethyl methacrylate (BSTMA), and 2-(2-bromoisobutyryloxy)ethylmethacrylate (BIEM) afforded the multifunctional random copolymer, P(OEGMA- co -BSTMA- co -BIEM), in which hydrophilic POEGMA can stabilize nanoparticles in water, PBSTMA can be converted into carboxyl groups, and PBIEM can be employed as a macromolecular atom radical transfer polymerization (ATRP) initiator. The ATRP of DEA and BMA using P(OEGMA- co -BSTMA- co -BIEM) as a macromolecular ATRP initiator led to the formation of the pH-responsive brush-type copolymer, P(OEGMA- co -BSTMA)- g -P(DEA- co - BMA). After hydrolysis by trifluoroacetic acid and post-functionalization the final polymeric prodrug, P(OEGMA- co -BUF- co -RGD)- g -P(DEA- co -BMA), was obtained with a drug content of ∼7.8 wt%. P(OEGMA- co -BUF- co -RGD)- g -P(DEA- co -BMA) can be assembled into nanoparticles (BUF- NP-RGD) in aqueous solution with a diameter of 148.4 ± 0.7 nm and a zeta potential of −7.6 ± 0.4 mV. BUF-NP-RGD exhibited controlled drug release in the presence of esterase. Additionally, P(OEGMA- co - BSMA)- g -P(DEA- co -BMA) showed a significant hemolysis effect at a pH comparable to that of endosomes/lysosomes. Cell viability and a tumor-bearing nude mouse model were employed to evaluate the anticancer efficacy of BUF-NP-RGD. It was revealed that BUF-NP-RGD showed improved anticancer performance compared with that of free BUF both in vitro and in vivo. Histological and immunochemical analysis further demonstrated that BUF-NP-RGD exhibited improved cell apoptosis, angiogenesis inhibition, and an anti-proliferation effect.
研究领域:
药学
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聚合物化学
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癌症研究
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2022
·
IF 3.571
Huan Wu,Hui Cheng,Shengyong Luo,Can Peng,An Zhou,Zhiwu Chen,Hong Wu,Qinglin Li
Huachansu (HCS) injection has been used for the clinical treatment of hepatocellular carcinoma (HCC) patients in China for more than thirty years. However, the underlying mechanisms of HCS injection in inhibiting HCC remains unclear. In this study, we aimed to evaluate the effects of HCS injection on HCC both in vitro and in vivo and to systematically explore the underlying mechanisms of HCS’s actions against HCC using an ultrahigh-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS)-based cellular metabolomics and lipidomics approach. MTT and DAPI staining were performed to evaluate the effects of HCS injection on cell proliferation and apoptosis , respectively, in human HepG2 HCC cells with and without HCS treatment. An H22 hepatoma-bearing mouse model was employed to investigate the anti-HCC action of HCS injection in vivo. A UPLC-HRMS-based cellular metabolomics and lipidomics method was employed to characterize cellular metabolite fingerprinting, to identify potential biomarkers associated with the effect of HCS injection on the inhibition of HCC and to explore the anti-HCC mechanisms of HCS injection from the perspective of cellular metabolism. As a result, HCS injection inhibited the proliferation of HepG2 cells and induced their apoptosis. Body weight loss, sarcoma weights and volumes of H22 hepatoma-bearing mice in the HCS treatment group were significantly attenuated compared to those in the model group. Twenty-five biomarkers responsible for the intervention effect of HCS were screened and annotated using UPLC-HRMS-based cellular metabolomics and lipidomics. Among these biomarkers, two cellular metabolites, uridine diphosphate- N -acetylglucosamine (UDP-GlcNAc) and glutathione , were confirmed unambiguously using the reference substances. Metabolic pathway analysis revealed that the anti-HCC effects of HCS injection primarily involved the metabolism of glutathione, cysteine and methionine , sphingolipid , fatty acid biosynthesis, amino sugar and nucleotide sugars . As evidenced by western blotting experiments, the changes in UDP-GlcNAc content in response to HCS injection were linked to the inhibition of UDP-GlcNAc pyrophosphorylase 1 (UAP1) expression in HepG2 cells. In conclusion, HCS injection has a curative anti-HCC effect, and a UPLC-HRMS-based cellular metabolomics and lipidomics approach combined with further confirmatory experiments is a promising means of discovering its underlying mechanisms.
研究领域:
肿瘤学
·
药理学
·
代谢组学
·
脂质组学
✓ 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）