The anti-tumor efficacy of 20(S)-protopanaxadiol, an active metabolite of ginseng, according to fasting on hepatocellular carcinoma

Li, Wenzhen; Wang, Yifan; Zhou, Xinbo; Pan, Xiaohong; Lü, Junhong; Sun, Hongliu; Xie, Zeping; Chen, Shayan; Xue, Guanhua

doi:10.1016/j.jgr.2021.06.002

Cited by 5 publications

(4 citation statements)

References 24 publications

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“…29,85,86 Considering that AMPK serves as an energy sensor and holds a crucial role in glucose sensing and energy regulation, we first screened silibinin as an optimal AMPK activator. This function is consistently with four well-known fasting mimetics, metformin, 29,87 aspirin, 39,40,88 20(S)-protopanaxadiol, 41,42 and resveratrol. 43,44 To further demonstrate that silibinin is a fasting mimetic, we determined the intracellular ATP levels and glucose consumption.…”

Section: Discussionsupporting

confidence: 63%

“…37,38 Aspirin, the inhibitor of enzyme cyclooxygenase and defined as another caloric-restriction mimetic, could inhibit non-small cell lung cancer cells and liver cancer cells growth by activating AMPK pathway. 15,39,40 Meanwhile, traditional Chinese medicine extracted compounds (such as: 20(S)-protopanaxadiol 41,42 and resveratrol 43,44 ) are detected as fasting mimetics to activate AMPK pathway. 45 Given AMPK's involvement in modulating metabolic dysregulation, mitochondrial dynamics and functions-hallmarks of cancer, AMPK presents as a promising target for cancer therapies.…”

Section: Introductionmentioning

confidence: 99%

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Silibinin, a potential fasting mimetic, inhibits hepatocellular carcinoma by triggering extrinsic apoptosis

Xiao,

Jiang,

Yuan

et al. 2024

MedComm

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Fasting, without inducing malnutrition, has been shown to have various beneficial effects, including the inhibition of tumor initiation and progression. However, prolonged fasting poses challenges for many cancer patients, particularly those in intermediate and terminal stages. Thus, there is an urgent need for the development of fasting mimetics which harness the protective effects of fasting but more suitable for patients. In this study, we first highlighted the pivotal role of silibinin in AMP‐activated protein kinase (AMPK) pathway and may serve, as a potential fasting mimetic via screening hepatoprotective drugs. Further metabolic analysis showed that silibinin inhibited the adenosine triphosphate (ATP) levels, glucose uptake and diminished glycolysis process, which further confirmed that silibinin served as a fasting mimetic. In addition, fasting synergized with silibinin, or used independently, to suppress the growth of hepatocellular carcinoma (HCC) in vivo. Mechanistically, silibinin upregulated death receptor 5 (DR5) through AMPK activation, and thus promoting extrinsic apoptosis and inhibiting HCC growth both in vitro and in vivo. Inhibition of AMPK using small interfering RNA (siRNA) or compound C, an AMPK inhibitor, significantly attenuated the upregulation of DR5 and the apoptotic response induced by silibinin. These findings suggest that silibinin holds promise as a fasting mimetic and may serve as an adjuvant drug for HCC treatment.

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Section: Discussionsupporting

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Silibinin, a potential fasting mimetic, inhibits hepatocellular carcinoma by triggering extrinsic apoptosis

Xiao,

Jiang,

Yuan

et al. 2024

MedComm

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“…Preclinical and clinical studies demonstrate that fasting has a great potential for cancer therapy 11 , 46 , 47 . Evidence indicates that fasting not only induces apoptosis of cancer cells but significantly sensitizes hepatocellular carcinoma (HCC) cell to antineoplastic agents 48 , 49 , 50 . YAP hyperactivation drives initiation and progression of multiple cancer types and resistance to various targeted and chemotherapies 51 .…”

Section: Discussionmentioning

confidence: 99%

YAP regulates the liver size during the fasting-refeeding transition in mice

Fan

Cai

et al. 2023

Acta Pharmaceutica Sinica B

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“…Ginsenosides such as ginsenoside-Rh2 (Rh2) and ginsenoside-Rg3 (Rg3) and their metabolites protopanaxatriol (PPT) and protopanaxadiol (PPD) have antioxidant, antitumor, anti-inflammatory and immunomodulatory activities [ [47] , [48] , [49] , [50] , [51] ]. For instance, Rg3 can significantly reduce the activity of NF-kB, elevate caspase-3 expression, and inhibit VEGF expression [ [52] , [53] , [54] , [55] , [56] ]. These effects of KRG may be beneficial to symptoms of post-COVID as well autoimmune problems, persistent chronic inflammation, and hormonal imbalance as a consequence of changes in the hypothalamic-pituitary-adrenal axis [ 7 , 57 ].…”

Section: Ginseng and Endometriosismentioning

confidence: 99%