20(S)-Protopanaxadiol blocks cell cycle progression by targeting epidermal growth factor receptor

Zhang, Tiehua; Liang, Yuan; Zuo, Peng; Jing, Siyuan; Li, Tiezhu; Wang, Yongjun; Lv, Chengyu; Li, Da; Zhang, Jie; Wei, Zhengyi

doi:10.1016/j.fct.2019.111017

Cited by 32 publications

(9 citation statements)

References 54 publications

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“…7,8 Natural products have attracted considerable attention for the wide range of human health benefits. 9,10 Dihydrochalcones are important natural products, which exhibit antioxidant, anti-inflammatory, antibacterial, antidiabetic, anticancer, and cardioprotective activities. 11,12 They are mainly present in the edible species of Lithocarpus, Rubus, Malus, and Averrhoa.…”

Section: Introductionmentioning

confidence: 99%

E Se tea alleviates acetaminophen-induced liver injury by activating the Nrf2 signaling pathway

Zhang

Zhao

et al. 2022

Food Funct.

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Section: Introductionmentioning

confidence: 99%

E Se tea alleviates acetaminophen-induced liver injury by activating the Nrf2 signaling pathway

Zhang

Zhao

et al. 2022

Food Funct.

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“…[19] Protopanaxadiol (PPD), a main active metabolite of ginseng, possesses significant anticancer effects via inhibiting the proliferation and metastasis of various malignant tumors including colorectal cancer, [20] triplenegative breast cancer, [21] endometrial cancer [22] and lung cancer. [23] Although several studies have explored the potential anti-cancer mechanisms of PPD, including regulating PI3K/ Akt, [24] EGFR/MAPK [25] and STAT3/Twist1 [26] pathways, the direct pharmacological targets of PPD in colorectal cancer cells havenot been identified.…”

Section: Introductionmentioning

confidence: 99%

Photoaffinity Labeling‐Based Chemoproteomic Strategy Reveals RBBP4 as a Cellular Target of Protopanaxadiol against Colorectal Cancer Cells

et al. 2022

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Protopanaxadiol (PPD), a main ginseng metabolite, exerts powerful anticancer effects against multiple types of cancer; however, its cellular targets remain elusive. Here, we synthesized a cell-permeable PPD probe via introducing a bifunctional alkyne-containing diazirine photo-crosslinker and performed a photoaffinity labeling-based chemoproteomic study. We identified retinoblastoma binding protein 4 (RBBP4), a chromatin remodeling factor, as an essential cellular target of PPD in HCT116 colorectal cancer cells. PPD significantly decreased RBBP4-dependent trimethylation at lysine 27 of histone H3 (H3K27me3), a crucial epigenetic marker that correlates with histologic signs of colorectal cancer aggressiveness, and PPD inhibition of proliferation and migration of HCT116 cells was antagonized by RBBP4 RNA silencing. Collectively, our study highlights a previously undisclosed anti-colorectal cancer cellular target of the ginseng metabolite and advances the fundamental understanding of RBBP4 functions via a chemical biology strategy.

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“…Reverse transcription and PCR amplification were carried out with TransScript one-step gDNA removal and cDNA synthesis supermix kit (Transgen Biotech Co., Ltd., Beijing, China). Quantitative real-time PCR was conducted using CFX96™ real-time system (Bio-rad®, Hercules, CA, USA) along with the primer pairs listed in the past article of our team [ 20 ]. The relative expression levels of mRNA were calculated by the 2 - ΔΔ CT method normalized with the GAPDH RNA level.…”

Section: Methodsmentioning

confidence: 99%

Identification of 20(S)-Ginsenoside Rh2 as a Potential EGFR Tyrosine Kinase Inhibitor

Liang

Zhao

Zou

et al. 2022

Oxidative Medicine and Cellular Longevity

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As the main active ingredients of Panax ginseng, ginsenosides possess numerous bioactivities. Epidermal growth factor receptor (EGFR) was widely used as a valid target in anticancer therapy. Herein, the EGFR targeting activities of 20(S)-ginsenoside Rh2 (20(S)-Rh2) and the relationship of their structure-activity were investigated. Homogeneous time-resolved fluorescence assay showed that 20(S)-Rh2 significantly inhibited the activity against EGFR kinase. 20(S)-Rh2 was confirmed to effectively inhibited cell proliferation in a dose-dependent manner by MTT assay. Furthermore, quantitative real-time PCR and western blotting analysis revealed that 20(S)-Rh2 inhibited A549 cells growth via the EGFR-MAPK pathway. Meanwhile, 20(S)-Rh2 could promote cell apoptosis, block cell cycle, and reduce cell migration of A549 cells, respectively. In silico, the result suggested that both hydrophobic interactions and hydrogen-bonding interactions could contribute to stabilize their binding. Molecular dynamics simulation showed that the side chain sugar moiety of 20(S)-Rh2 was too flexible to be fixed at the active site of EGFR. Collectively, these findings suggested that 20(S)-Rh2 might serve as a potential EGFR tyrosine kinase inhibitor.

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20(S)-Protopanaxadiol blocks cell cycle progression by targeting epidermal growth factor receptor

Cited by 32 publications

References 54 publications

E Se tea alleviates acetaminophen-induced liver injury by activating the Nrf2 signaling pathway

E Se tea alleviates acetaminophen-induced liver injury by activating the Nrf2 signaling pathway

Photoaffinity Labeling‐Based Chemoproteomic Strategy Reveals RBBP4 as a Cellular Target of Protopanaxadiol against Colorectal Cancer Cells

Identification of 20(S)-Ginsenoside Rh2 as a Potential EGFR Tyrosine Kinase Inhibitor

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