Guizhi Fuling Decoction inhibiting the PI3K and MAPK pathways in breast cancer cells revealed by HTS2 technology and systems pharmacology

Dai, Yifei; Qiang, Weijie; Yu, Xiankuo; Cai, Siwei; Lin, Kequan; Xie, Liang; Lan, Xun; Wang, Dong

doi:10.1016/j.csbj.2020.05.004

Cited by 37 publications

(16 citation statements)

References 61 publications

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“…HTS 2 can also be used to explore the mechanisms of action of anticancer herbs. Combined with network pharmacology, HTS 2 was used to unveil the biological basis of medicine with complex ingredients, such as traditional Chinese medicine (TCM) in cancer therapy (41,42) as well as other diseases (43). Zheng et al utilized HTS 2 to measure the function of 166 compounds derived from TCM on 420 antitumor or immune-related genes.…”

Section: The Application Of Hts 2 In Cancer Drug Discovery By Targeting Transcriptional Reprogrammingmentioning

confidence: 99%

“…Guizhi Fuling Decoction (GFD) is a classic TCM prescription used in treating gynecological tumors with an unclear mechanism. Dai et al applied HTS 2 technology along with systemic pharmacology to clarify the mechanisms of GFD in treating breast cancer; this revealed that GFD represses breast cancer through the inhibition of PI3K and MAPK signaling pathways (42).…”

Section: The Application Of Hts 2 In Cancer Drug Discovery By Targeting Transcriptional Reprogrammingmentioning

confidence: 99%

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High-Throughput Strategies for the Discovery of Anticancer Drugs by Targeting Transcriptional Reprogramming

Huang

Xiaohong

et al. 2021

Front. Oncol.

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Transcriptional reprogramming contributes to the progression and recurrence of cancer. However, the poorly elucidated mechanisms of transcriptional reprogramming in tumors make the development of effective drugs difficult, and gene expression signature is helpful for connecting genetic information and pharmacologic treatment. So far, there are two gene-expression signature-based high-throughput drug discovery approaches: L1000, which measures the mRNA transcript abundance of 978 “landmark” genes, and high-throughput sequencing-based high-throughput screening (HTS2); they are suitable for anticancer drug discovery by targeting transcriptional reprogramming. L1000 uses ligation-mediated amplification and hybridization to Luminex beads and highlights gene expression changes by detecting bead colors and fluorescence intensity of phycoerythrin signal. HTS2 takes advantage of RNA-mediated oligonucleotide annealing, selection, and ligation, high throughput sequencing, to quantify gene expression changes by directly measuring gene sequences. This article summarizes technological principles and applications of L1000 and HTS2, and discusses their advantages and limitations in anticancer drug discovery.

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Section: The Application Of Hts 2 In Cancer Drug Discovery By Targeting Transcriptional Reprogrammingmentioning

confidence: 99%

Section: The Application Of Hts 2 In Cancer Drug Discovery By Targeting Transcriptional Reprogrammingmentioning

confidence: 99%

High-Throughput Strategies for the Discovery of Anticancer Drugs by Targeting Transcriptional Reprogramming

Huang

Xiaohong

et al. 2021

Front. Oncol.

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“…Recent studies have shown that some TCM formulas containing CR have good antitumor effects. Dai et al reported that Guizhi Fuling Decoction could play a role in the treatment of breast cancer by interfering with the phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) signaling pathways [9]. Another study showed that Danggui Sini Decoction, a traditional classic recipe, could affect some key biological processes, such as apoptosis and the cell cycle, involved in the survival and growth of gastric cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Cinnamomi Ramulus inhibits the growth of colon cancer cells via Akt/ERK signaling pathways

et al. 2022

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Background Colon cancer (CC) ranks the second highest mortality rate among malignant tumors worldwide, and the current mainstream treatment regimens are not very effective. The unique efficacy of Chinese herb medicine (CHM) for cancer has recently attracted increasing attention. Cinnamomi Ramulus (CR), as a classic CHM, has been widely used in the treatment of a variety of diseases for hundreds of years in China, but its specific pharmacological mechanism against CC needs to be fully evaluated. Methods TCMSP and China National Knowledge Infrastructure database were utilized to predict the candidate ingredients of CR, and TCMSP and SwissTargetPrediction database were also employed to predict the drug targets of the candidate ingredients from CR. We subsequently evaluated the therapeutic effect of CR by orally administrating it on CC-bearing mice. Next, we further identified the potential CC-related targets by using Gene Expression Omnibus (GEO) database. Based on these obtained targets, the drug/disease-target PPI networks were constructed using Bisogenet plugin of Cytoscape. The potential core therapeutic targets were then identified through topological analysis using CytoNCA plugin. GO and KEGG enrichment analyses were performed to predict the underlying mechanism of CR against CC. Furthermore, these in silico analysis results were validated by a series of cellular functional and molecular biological assays. UPLC–MS/MS method and molecular docking analysis were employed to identify the potential key components from CR. Results In this study, we firstly found that CR has potential therapeutic effect on cancer. Then, oral administration of CR could inhibit the growth of CC cells in C57BL/6 mice, while inhibiting the viability and motility of CC cells in vitro. We obtained 111 putative core therapeutic targets of CR. Subsequent enrichment analysis on these targets showed that CR could induce apoptosis and cell cycle arrest in CC cells by blocking Akt/ERK signaling pathways, which was further experimentally verified. We identified 5 key components from the crude extract of CR, among which taxifolin was found most likely to be the key active component against CC. Conclusions Our results show that CR as well as its active component taxifolin holds great potential in treatment of CC.

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“…Large-scale leaps will also present multiple dimensions of the three-dimensional network from small chemical molecules, genes to proteins . Therefore, systemic pharmacology can solve a series of problems brought about by the complexity of TCM, which provides a new approach to predict the active ingredients and candidate targets through a holistic process of active compound screening, target “fishing”, component–target–disease (C–T–D) network construction, and target enrichment analysis. − …”

Section: Introductionmentioning

confidence: 99%

Anti-Inflammatory Effects and Mechanisms of Pudilan Antiphlogistic Oral Liquid

Tian

Bao

et al. 2021

ACS Omega

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Pudilan antiphlogistic oral liquid (PDL) is a commercial traditional Chinese medicine widely used in the treatment of a variety of inflammatory diseases. However, the specific mechanisms of PDL’s anti-inflammatory effects have not been fully understood. In this research, five classic inflammatory models and a network pharmacology-based strategy were utilized to evaluate its anti-inflammatory efficacy and elucidate its multicomponent and multitarget mode of the anti-inflammatory mechanism. A systems pharmacology approach was carried out via a holistic process of active compound screening, target acquisition, network construction, and further analysis. The potential component–target-associated anti-inflammatory mechanisms of PDL were further verified both in vivo and in vitro . The results showed that PDL exhibited a proven anti-inflammatory effect on multiple types of inflammatory models, including β-hemolytic streptococcus-induced acute pharyngitis, LPS-induced acute lung injury, xylene-induced ear swelling, carrageenan-induced paw edema, and acetic acid-induced capillary permeability-increasing models. Systems pharmacology analysis predicted 45 ingredients of PDL that interact with 185 targets, of which 38 overlapped with the inflammation-related targets. Furthermore, KEGG pathway analysis showed that the predicted targets were mainly involved in hypoxia-inducible factor (HIF)-1, tumor necrosis factor (TNF), nuclear factor kappa-B (NF-κB), and NOD-like receptor (NLR) pathways. Both in vivo and in vitro experiments clarified that PDL has anti-inflammatory potency by inhibiting PI3K and p38 phosphorylation and activating the NLRP3 inflammasome. Our results suggested that PDL has an efficient and extensive anti-inflammatory effect, and its anti-inflammatory mechanisms may involve multiple inflammatory-associated signaling pathways, including HIF-1- and TNF-mediated pathways and NLRP3 inflammasome activation.

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Guizhi Fuling Decoction inhibiting the PI3K and MAPK pathways in breast cancer cells revealed by HTS2 technology and systems pharmacology

Cited by 37 publications

References 61 publications

High-Throughput Strategies for the Discovery of Anticancer Drugs by Targeting Transcriptional Reprogramming

High-Throughput Strategies for the Discovery of Anticancer Drugs by Targeting Transcriptional Reprogramming

Cinnamomi Ramulus inhibits the growth of colon cancer cells via Akt/ERK signaling pathways

Anti-Inflammatory Effects and Mechanisms of Pudilan Antiphlogistic Oral Liquid

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