New insight into 20(S)-ginsenoside Rh2 against T-cell acute lymphoblastic leukemia associated with the gut microbiota and the immune system

Xia, Ting; Zhang, Bo; Yu, Li; Fang, Bin; Zhu, Xiaoxuan; Xu, Bicheng; Zhang, Jin; Fang, Jian‐Pei

doi:10.1016/j.ejmech.2020.112582

Cited by 39 publications

(13 citation statements)

References 73 publications

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“…In addition, 20(S)-ginsenoside Rh2 (GRh2) also regulates PI3K/Akt/mTOR signaling pathway. 41 In general, cancer cell development need overcome the energy consumption and oxygen supplement, therefore, autophagy played the major role on providing more ATP to cancer cell and defeating hypoxic stress. Therefore, targeting inhibiting T-ALL autophagy provided a promising strategy to increase treatment efficacy or sensitivity to the chemotherapy.…”

Section: Autophagy and T-cell Acute Lymphoblastic Leukemia (T-all)mentioning

confidence: 99%

Role of Autophagy and Apoptosis in Acute Lymphoblastic Leukemia

Huang

2021

Cancer Control

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Background: Acute lymphoblastic leukemia (ALL) is a malignant disease characterized by an excessive number of immature lymphocytes, including immature precursors of both B- and T cells. ALL affects children more often than adults. Immature lymphocytes lead to arrested differentiation and proliferation of cells. Its conventional treatments involve medication with dexamethasone, vincristine, and other anticancer drugs. Although the current first-line drugs can achieve effective treatment, they still cannot prevent the recurrence of some patients with ALL. Treatments have high risk of recurrence especially after the first remission. Currently, novel therapies to treat ALL are in need. Autophagy and apoptosis play important roles in regulating cancer development. Autophagy involves degradation of proteins and organelles, and apoptosis leads to cell death. These phenomena are crucial in cancer progression. Past studies reported that many potential anticancer agents regulate intracellular signaling pathways. Methods: The authors discuss the recent research findings on the role of autophagy and apoptosis in ALL. Results: The autophagy and apoptosis are widely used in the treatment of ALL. Most studies showed that many agents regulate autophagy and apoptosis in ALL cell models, clinical trials, and ALL animal models. Conclusions: In summary, activating autophagy and apoptosis pathways are the main strategies for ALL treatments. For ALL, combining new drugs with traditional chemotherapy and glucocorticoids treatments can achieve the greatest therapeutic effect by activating autophagy and apoptosis.

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Section: Autophagy and T-cell Acute Lymphoblastic Leukemia (T-all)mentioning

confidence: 99%

Role of Autophagy and Apoptosis in Acute Lymphoblastic Leukemia

Huang

2021

Cancer Control

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“…Notably, ATP6AP2 knock-in significantly decreases the relative abundance of Lachnospiraceae_NK4A136 genus (Fig. 6 E), which is known to be positively associated with anti-tumor immune factors, intestinal barrier-related factors, and anti-inflammatory response [ 28 ]. Additionally, ATP6AP2 knock-in also leads to the shrink of Bacteroides genus (Fig.…”

Section: Resultsmentioning

confidence: 99%

(Pro)renin receptor promotes colorectal cancer progression through inhibiting the NEDD4L-mediated Wnt3 ubiquitination and modulating gut microbiota

Wang

Ding

et al. 2023

Cell Commun Signal

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Background We previously found that (pro)renin receptor ((P)RR) augments Wnt3 protein without affecting Wnt3 gene transcription in colorectal cancer (CRC) cells, thus contributes to CRC initiation. The present study aims to investigate whether (P)RR further promotes CRC progression following oncogenesis and the related mechanisms. Notably, we deeply elaborate how (P)RR affects Wnt3 protein level and the key enzyme that mediates this process. Methods Immunohistochemistry, western blotting and immunofluorescence were performed to detect protein expression status. A kind of gastrointestinal epithelium-specific ATP6AP2 ((P)RR encoding gene) knock-in mice were generated using Crispr/Cas9 system. Results We found that increased (P)RR expression in primary CRC lesions is positively associated with higher Wnt3 protein level and disease progression. Progressive CRC presents less colocalization of Wnt3 and an E3 ubiquitin ligase NEDD4L in primary lesions than non-progressive CRC. In colon cancer cells, (P)RR dramatically inhibits the NEDD4L-mediated Wnt3 protein ubiquitination. ATP6AP2 knock-in mice show more diminished Wnt3-NEDD4L colocalization in their gut epithelium in comparison to wildtype mice. They also have abnormal gut bacterial flora distribution. Especially, Lachnospiraceae_NK4A136 and Bacteroides genus, which are generally protective against CRC, are suppressed in guts of ATP6AP2 knock-in mice. Conclusions Collectively, (P)RR promotes CRC progression through inhibiting the NEDD4L-mediated Wnt3 ubiquitination and modulating gut microbiota.

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“…20(R)-Rg3 increases the expression of NK activation receptors NKp44, NKp46, NKp30, and NK cell degranulation marker CD107a through activation of the MAPK/ERK pathway, thereby enhancing the killing activity of NK cells against tumor cells ( Lee et al, 2022 ). Xia et al observed that GRh2 could regulate immune factors (e.g., IL4, IL6, CD3, CD45, and INF-γ) to enhance splenic immunity and increase the number of NK cells, which are important in tumor prevention and treatment ( Xia et al, 2020 ). In addition to digestive system tumors, in MCF7 breast cells, GRh2 downregulates CASP1, INSL5, and OR52A1 and upregulates the expression of CLINT1, ST3GAL4, and C1orf198, induces an immune response and epigenetic methylation changes in tumors, enhances immunogenicity, and inhibits the growth of cancer cells ( Lee et al, 2018 ).…”

Section: Anti-tumor Mechanism Of Action Of the Active Ingredients Of ...mentioning

confidence: 99%

Research progress of ginseng in the treatment of gastrointestinal cancers

Song²,

Shi³

et al. 2022

Front. Pharmacol.

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Cancer has become one of the major causes of human death. Several anticancer drugs are available; howeve their use and efficacy are limited by the toxic side effects and drug resistance caused by their continuous application. Many natural products have antitumor effects with low toxicity and fewer adverse effects. Moreover, they play an important role in enhancing the cytotoxicity of chemotherapeutic agents, reducing toxic side effects, and reversing chemoresistance. Consequently, natural drugs are being applied as potential therapeutic options in the field of antitumor treatment. As natural medicinal plants, some components of ginseng have been shown to have excellent efficacy and a good safety profile for cancer treatment. The pharmacological activities and possible mechanisms of action of ginseng have been identified. Its broad range of pharmacological activities includes antitumor, antibacterial, anti-inflammatory, antioxidant, anti-stress, anti-fibrotic, central nervous system modulating, cardioprotective, and immune-enhancing effects. Numerous studies have also shown that throuth multiple pathways, ginseng and its active ingredients exert antitumor effects on gastrointestinal (GI) tract tumors, such as esophageal, gastric, colorectal, liver, and pancreatic cancers. Herein, we introduced the main components of ginseng, including ginsenosides, polysaccharides, and sterols, etc., and reviewed the mechanism of action and research progress of ginseng in the treatment of various GI tumors. Futhermore, the pathways of action of the main components of ginseng are discussed in depth to promote the clinical development and application of ginseng in the field of anti-GI tumors.

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New insight into 20(S)-ginsenoside Rh2 against T-cell acute lymphoblastic leukemia associated with the gut microbiota and the immune system

Cited by 39 publications

References 73 publications

Role of Autophagy and Apoptosis in Acute Lymphoblastic Leukemia

Role of Autophagy and Apoptosis in Acute Lymphoblastic Leukemia

(Pro)renin receptor promotes colorectal cancer progression through inhibiting the NEDD4L-mediated Wnt3 ubiquitination and modulating gut microbiota

Research progress of ginseng in the treatment of gastrointestinal cancers

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