20(<i>S</i>)‐Protopanaxadiol inhibits epithelial‐mesenchymal transition by promoting retinoid X receptor alpha in human colorectal carcinoma cells

Lu, Zeyuan; Liu, Hongyan; Fu, Wenwen; Wang, Yuchen; Geng, Jianan; Wang, Yaozhen; Yu, Xiaofeng; Wang, Quan; Xu, Huali; Sui, Dayun

doi:10.1111/jcmm.16054

Cited by 8 publications

(6 citation statements)

References 63 publications

(132 reference statements)

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“…[16][17][18] Ginseng, an herbal medicine with a variety of biological activities, has been widely used as an important traditional medicine for thousands of years. [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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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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“…Proto-ginsenoside of ginsenodiol type (PPD) has also been shown to have a significant inhibitory effect on breast cancer ( Zhang et al., 2018 ), uterine cancer ( Jo et al., 2021 ), prostate cancer ( Cao et al., 2014 ), and metastasis of cancer cells ( Lu et al., 2020 ). Although PPD has good pharmacological activity, it cannot be directly extracted from ginseng, it needs to be processed and transformed under the action of gut microbiota in vivo .…”

Section: Transformation and Modification Of Ginsenosides By Gut Micro...mentioning

confidence: 99%

Gut Microbiota: Therapeutic Targets of Ginseng Against Multiple Disorders and Ginsenoside Transformation

Chen

Zhang

Liu

et al. 2022

Front. Cell. Infect. Microbiol.

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Panax ginseng, as the king of Chinese herb, has significant therapeutic effects on obesity, type 2 diabetes mellitus, fatty liver disease, colitis, diarrhea, and many other diseases. This review systematically summarized recent findings, which show that ginseng plays its role by regulating gut microbiota diversity, and gut microbiota could also regulate the transformation of ginsenosides. We conclude the characteristics of ginseng in regulating gut microbiota, as the potential targets to prevent and treat metabolic diseases, colitis, neurological diseases, cancer, and other diseases. Ginseng treatment can increase some probiotics such as Bifidobacterium, Bacteroides, Verrucomicrobia, Akkermansia, and reduce pathogenic bacteria such as Deferribacters, Lactobacillus, Helicobacter against various diseases. Meanwhile, Bacteroides, Eubacterium, and Bifidobacterium were found to be the key bacteria for ginsenoside transformation in vivo. Overall, ginseng can regulate gut microbiome diversity, further affect the synthesis of secondary metabolites, as well as promote the transformation of ginsenosides for improving the absorptivity of ginsenosides. This review can provide better insight into the interaction of ginseng with gut microbiota in multiple disorders and ginsenoside transformation.

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“…Ginsenosides, the major active ingredients found in ginseng and other plants of the genus Panax, are very popular for their antioxidant, strengthening the immune system and many other activities 4,5 . Protopanaxadiol (PPD) is a major active metabolite from PPD‐type ginsenosides and possesses pleiotropic anticancer activities in many cancers 6–8 . Enhancing immunity is one of the main functions of ginsenosides.…”

Section: Introductionmentioning

confidence: 99%

Protopanaxadiol manipulates gut microbiota to promote bone marrow hematopoiesis and enhance immunity in cyclophosphamide‐induced immunosuppression mice

Cao

Liu

et al. 2023

MedComm

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Protopanaxadiol (PPD) has potential immunomodulatory effects, but the underlying mechanism remains unclear. Here, we explored the potential roles of gut microbiota in the immunity regulation mechanisms of PPD using a cyclophosphamide (CTX)‐induced immunosuppression mouse model. Our results showed that a medium dose of PPD (PPD‐M, 50 mg/kg) effectively ameliorated the immunosuppression induced by CTX treatment by promoting bone marrow hematopoiesis, increasing the number of splenic T lymphocytes and regulating the secretion of serum immunoglobulins and cytokines. Meanwhile, PPD‐M protected against CTX‐induced gut microbiota dysbiosis by increasing the relative abundance of Lactobacillus, Oscillospirales, Turicibacter, Coldextribacter, Lachnospiraceae, Dubosiella, and Alloprevotella and reducing the relative abundance of Escherichia‐Shigella. Importantly, PPD‐M lost the ability to promote bone marrow hematopoiesis and enhance immunity when the gut microbiota was depleted by broad‐spectrum antibiotics. Moreover, PPD‐M promoted the production of microbiota‐derived immune‐enhancing metabolites including cucurbitacin C, l‐gulonolactone, ceramide, DG, prostaglandin E2 ethanolamide, palmitoyl glucuronide, 9R,10S‐epoxy‐stearic acid, and 9′‐carboxy‐gamma‐chromanol. KEGG topology analysis showed that the PPD‐M treatment significantly enriched the sphingolipid metabolic pathway with ceramide as a main metabolite. Our findings reveal that PPD enhances immunity by manipulating gut microbiota and has the potential to be used as an immunomodulator in cancer chemotherapy.

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20(S)‐Protopanaxadiol inhibits epithelial‐mesenchymal transition by promoting retinoid X receptor alpha in human colorectal carcinoma cells

Cited by 8 publications

References 63 publications

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

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

Gut Microbiota: Therapeutic Targets of Ginseng Against Multiple Disorders and Ginsenoside Transformation

Protopanaxadiol manipulates gut microbiota to promote bone marrow hematopoiesis and enhance immunity in cyclophosphamide‐induced immunosuppression mice

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