Ginsenoside Rh2 inhibits hepatocellular carcinoma through β-catenin and autophagy

Yang, Zhiqing; Zhao, Tingting; Liu, Hongli; Zhang, Leida

doi:10.1038/srep19383

Cited by 60 publications

(53 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For instance, Rh2 was shown to induce autophagy in hepatocellular carcinoma and exert an anti-tumor effect [35]. Most recently, Rg2 was reported to exhibit neuronal and metabolic benefits through autophagy induction [36].…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rb2 Alleviates Hepatic Lipid Accumulation by Restoring Autophagy via Induction of Sirt1 and Activation of AMPK

Huang

Wang

Yang

et al. 2017

IJMS

View full text Add to dashboard Cite

Although Panax ginseng is a famous traditional Chinese medicine and has been widely used to treat a variety of metabolic diseases including hyperglycemia, hyperlipidemia, and hepatosteatosis, the effective mediators and molecular mechanisms remain largely unknown. In this study we found that ginsenoside Rb2, one of the major ginsenosides in Panax ginseng, was able to prevent hepatic lipid accumulation through autophagy induction both in vivo and in vitro. Treatment of male db/db mice with Rb2 significantly improved glucose tolerance, decreased hepatic lipid accumulation, and restored hepatic autophagy. In vitro, Rb2 (50 µmol/L) obviously increased autophagic flux in HepG2 cells and primary mouse hepatocytes, and consequently reduced the lipid accumulation induced by oleic acid in combination with high glucose. Western blotting analysis showed that Rb2 partly reversed the high fatty acid in combination with high glucose (OA)-induced repression of autophagic pathways including AMP-activated protein kinase (AMPK) and silent information regulator 1 (sirt1). Furthermore, pharmacological inhibition of the sirt1 or AMPK pathways attenuated these beneficial effects of Rb2 on hepatic autophagy and lipid accumulation. Taken together, these results suggested that Rb2 alleviated hepatic lipid accumulation by restoring autophagy via the induction of sirt1 and activation of AMPK, and resulted in improved nonalcoholic fatty liver disease (NAFLD) and glucose tolerance.

show abstract

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rb2 Alleviates Hepatic Lipid Accumulation by Restoring Autophagy via Induction of Sirt1 and Activation of AMPK

Huang

Wang

Yang

et al. 2017

IJMS

View full text Add to dashboard Cite

show abstract

“…Numerous ginsenosides have been reported to be important regulators of autophagy and exert various biological activities either by inducing autophagy or by inhibiting autophagy. The ginsenosides that serve as autophagy inducer include CK, Rg3, Rh2, Rg1, Rg2, and F2 . Meanwhile, the ginsenosides that can inhibit autophagy include Ro, Rg3, Rg1, and Rb1 (Fig.…”

Section: Cellular Stress Response Mechanisms Regulated By Ginsenosidesmentioning

confidence: 99%

“…CK‐provoked autophagy was demonstrated to suppress the growth of human colon cancer and melanoma cells . Moreover, Rh2 inhibited cancer stem cell‐like cells in both human skin squamous cell carcinoma and human hepatocellular carcinoma cells; this effect was abolished by the inhibition of Rh2‐activated autophagy. In addition, autophagy also impairs tumor metastasis.…”

Section: Cellular Stress Response Mechanisms Regulated By Ginsenosidesmentioning

confidence: 99%

Cellular stress response mechanisms as therapeutic targets of ginsenosides

2017

Medicinal Research Reviews

View full text Add to dashboard Cite

Ginseng, one of the most widely used traditional herbal medicines and dietary supplements, has historically been recognized as a tonic herb and adaptogen that can enhance the body's tolerance to various adversities. Ginsenosides are a diverse group of steroidal saponins that comprise the major secondary metabolites of ginseng and are responsible for its multiple pharmacological effects. Emerging evidence suggests that hormetic phytochemicals produced by environmentally stressed plants can activate the moderate cellular stress response mechanisms at a subtoxic level in humans, which may enhance tolerance against severe dysfunction or disease. In this review, we initially describe the role of ginsenosides in the chemical defense of plants from the genus Panax suffering from biotic and abiotic stress. Next, we summarize the diverse evolutionarily conserved cellular stress response pathways regulated by ginsenosides and the subsequent stress tolerance against various dysfunctions or diseases. Finally, the structure-activity relationship involved in the effect of ginsenosides is also analyzed. The evidence presented in this review implicates that ginseng as "the King of all herbs" could be regarded as a well-characterized example of the critical role of cellular stress response mechanisms in understanding the health benefits provided by herbal medicines from an evolutionary and ecological perspective.

show abstract

“…The exact role of autophagy in cancer remains controversial. A number of studies provide evidence that autophagy suppresses tumorigenesis (18,19), whereas other studies propose that autophagy is associated with tumor development and protects tumor cells from apoptosis (20,21). In addition, a role for autophagy in the chemosensitivity of cancer cells has been identified; Wu et al (22) reported that autophagy may facilitate the resistance of lung adenocarcinoma cells to cisplatin treatment by the activation of the AMP-activated protein kinase/mechanistic target of rapamycin signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Role of 5‑Aza‑CdR in mitomycin‑C chemosensitivity of T24 bladder cancer cells

et al. 2017

View full text Add to dashboard Cite

Abstract. Chemotherapeutic insensitivity is one of key obstacles to effectively treating muscle invasive bladder cancer. 5-Aza-2'-deoxycytidine (5-Aza-CdR) has been identified as a tumor suppressive agent in various types of cancer. The aim of the present study was to identify the effects of 5-Aza-CdR on the mitomycin-C (MMC) chemosensitivity of T24 bladder cancer cells and investigate the underlying mechanisms. T24 cells were treated with a combination of MMC and 5-Aza-CdR at various concentrations. The rates of proliferation and apoptosis were assessed by an MTT assay and flow cytometry, respectively. The expression of drug resistance-associated proteins, including P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1), and autophagy-associated proteins, including beclin 1, nucleoporin 62 (p62) and autophagy protein 5 (ATG5) were detected with western blotting. Treatment with 5-Aza-CdR significantly promoted the MMC chemosensitivity of T24 cells. The proliferation of T24 cells was significantly inhibited with increasing 5-Aza-CdR concentration, whereas apoptosis was significantly increased. This was associated with the decreased expression of P-gp, MRP1, beclin 1, p62 and ATG5. In conclusion, 5-Aza-CdR enhanced MMC chemosensitivity in bladder cancer T24 cells, which may be caused by the suppression of drug resistance-and autophagy-associated proteins.

show abstract

Ginsenoside Rh2 inhibits hepatocellular carcinoma through β-catenin and autophagy

Cited by 60 publications

References 48 publications

Ginsenoside Rb2 Alleviates Hepatic Lipid Accumulation by Restoring Autophagy via Induction of Sirt1 and Activation of AMPK

Ginsenoside Rb2 Alleviates Hepatic Lipid Accumulation by Restoring Autophagy via Induction of Sirt1 and Activation of AMPK

Cellular stress response mechanisms as therapeutic targets of ginsenosides

Role of 5‑Aza‑CdR in mitomycin‑C chemosensitivity of T24 bladder cancer cells

Contact Info

Product

Resources

About