20 (S)-ginsenoside Rh2 inhibits colorectal cancer cell growth by suppressing the Axl signaling pathway in vitro and in vivo

Zhang, Haibo; Yi, Junkoo; Huang, Hai; Park, Sijun; Kwon, Wookbong; Kim, Eungyung; Jang, Soyoung; Kim, Siyong; Choi, Seong‐Kyoon; Yoon, Duhak; Kim, Sung-Hyun; Liu, Kangdong; Dong, Zigang; Ryoo, Zae Young; Kim, Myoung Ok

doi:10.1016/j.jgr.2021.07.004

Cited by 15 publications

(5 citation statements)

References 60 publications

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“…Tumor resistance has been linked to AXL signaling activation, and through binding to EGFR and other HER family members like MET and PDGFR, AXL can facilitate the formation of targeted treatment resistance [23][24][25] . AXL expression may also be increased by the use of target therapeutic products [26.27] .…”

Section: Discussionmentioning

confidence: 99%

AXL up-regulates PD-L1 inducing gefitinib resistance in EGFR mutated NSCLC

Ming-sheng

Xiong

Wang

et al. 2023

Preprint

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Targeted therapy for lung cancer research has advanced quickly in recent years, particularly EGFR-TKIs in the grouping of EGFR-mutant lung cancer, however clinical treatment has encountered difficulties with acquired drug resistance. Due to their great specificity, few adverse reactions, and prolonged tumor control duration, immune checkpoint inhibitors PD-1 and PD-L1 antibodies have emerged as a new therapy approach for NSCLC with the advancement of tumor biology. AXL, a gene that codes for receptor tyrosine kinases, has been linked to the growth, treatment resistance, and immunological imbalance of cancer cells. Its protein has been found to be abnormally expressed in NSCLC cancer tissues. Our study shows a positive regulatory link between AXL and PD-L1 expression, and AXL can upregulate PD-L1 to facilitate the development of acquired drug resistance in EGFR-mutant lung cancer treated with gefitinib. We offer additional understandings for AXL to overcome the gefitinib resistance mechanism in NSCLC, while also providing ideas for addressing targeted therapy resistance.

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Section: Discussionmentioning

confidence: 99%

AXL up-regulates PD-L1 inducing gefitinib resistance in EGFR mutated NSCLC

Ming-sheng

Xiong

Wang

et al. 2023

Preprint

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“…Furthermore, in our study the content of minor ginsenoside Rh 2 in the SLPN-instant beverage was 1.64 ± 0.14 mg/g-DW, being five times higher than that in SLPN. G-Rh 2 could inhibit colorectal cancer cell growth ( 56 ), suppress the proliferation of A549 cells ( 57 ), breast cancer cell growth ( 58 ), and moreover the combination of G-Rh 2 could induce lung cancer ( 59 ). Up to date, G-Rh 2 is being developed as a new antitumor drug.…”

Section: Discussionmentioning

confidence: 99%

An instant beverage rich in nutrients and secondary metabolites manufactured from stems and leaves of Panax notoginseng

Liang

Liu²,

Li³

et al. 2022

Front. Nutr.

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IntroductionRadix Notoginseng, one of the most famous Chinese traditional medicines, is the dried root of Panax notoginseng (Araliaceae). Stems and leaves of P. notoginseng (SLPN) are rich in secondary metabolites and nutrients, and authorized as a food resource, however, its utilization needs further research.MethodsA SLPN-instant beverage was manufactured from SLPN through optimization by response surface design with 21-fold of 48.50% ethanol for 39 h, and this extraction was repeated twice; the extraction solution was concentrated to 1/3 volume using a vacuum rotatory evaporator at 45°C, and then spray dried at 110°C. Nutritional components including 14 amino acids, ten mineral elements, 15 vitamins were detected in the SLPN-instant beverage; forty-three triterpenoid saponins, e.g., ginsenoside La, ginsenoside Rb3, notoginsenoside R1, and two flavonoid glycosides, as well as dencichine were identified by UPLC-MS.ResultsThe extraction rate of SLPN-instant beverage was 37.89 ± 0.02%. The majority nutrients were Gly (2.10 ± 0.63 mg/g), His (1.23 ± 0.07 mg/g), α-VE (18.89 ± 1.87 μg/g), β-VE (17.53 ± 1.98 μg/g), potassium (49.26 ± 2.70 mg/g), calcium (6.73 ± 0.27 mg/g). The total saponin of the SLPN-instant beverage was 403.05 ± 34.98 mg/g, majority was notoginsenoside Fd and with contents of 227 ± 2.02 mg/g. In addition, catechin and γ-aminobutyric acid were detected with levels of 24.57 ± 0.21 mg/g and 7.50 ± 1.85 mg/g, respectively. The SLPN-instant beverage showed good antioxidant activities with half maximal inhibitory concentration (IC50) for scavenging hydroxyl (OH–) radicals, superoxide anion (O2–) radicals, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS+) radicals were 0.1954, 0.2314, 0.4083, and 0.3874 mg/mL, respectively.ConclusionWe optimized an analytical method for in depth analysis of the newly authorized food resource SLPN. Together, an instant beverage with antioxidant activity, rich in nutrients and secondary metabolites, was manufactured from SLPN, which may improve the utilization of SLPN.

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“…Liu et al observed that GRh2 induced cycle arrest and apoptosis in drug-resistant colorectal cancer cells (LoVo/5-FU and HCT-8/5-FU) ( Liu T et al, 2018 ). Zhang et al observed that GRh2 induced apoptosis by activating the p53 pathway, upregulating Bax expression, decreasing Bcl2 expression, and inducing apoptosis in HCT116 and SW480 colorectal cancer cells ( Zhang H et al, 2022 ). In pancreatic cancer cells, GRh2 also induces apoptosis in Bxpc-3 cells by upregulating Bax, caspase-3, and caspase-9, and downregulating Bcl-2, survivin, cyclin D1, MMP-2, and MMP-9 ( Li et al, 2021a ).…”

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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20 (S)-ginsenoside Rh2 inhibits colorectal cancer cell growth by suppressing the Axl signaling pathway in vitro and in vivo

Cited by 15 publications

References 60 publications

AXL up-regulates PD-L1 inducing gefitinib resistance in EGFR mutated NSCLC

AXL up-regulates PD-L1 inducing gefitinib resistance in EGFR mutated NSCLC

An instant beverage rich in nutrients and secondary metabolites manufactured from stems and leaves of Panax notoginseng

Research progress of ginseng in the treatment of gastrointestinal cancers

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