RETRACTED: Hispidulin inhibits hepatocellular carcinoma growth and metastasis through AMPK and ERK signaling mediated activation of PPARγ

Han, Mei; Gao, Hui; Ju, Ping; Gao, Mingquan; Yuan, Yifei; Chen, Xuehong; Liu, Kai-li; Han, Yantao; Han, Ze‐Guang

doi:10.1016/j.biopha.2018.04.014

Cited by 75 publications

(57 citation statements)

References 46 publications

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“…For instance, thapsigargin causes ERS and sensitizes human esophageal cancer to TRAIL-induced apoptosis via AMPK activation [55]. Our previous studies indicated that hispidulin exhibits anti-cancer activity by activating the AMPK signaling pathway in a variety of tumor cells, including glioblastoma, ovarian cancer cells, colorectal cancer, and hepatocellular carcinoma [21,22,27,28]. However, little is known as to whether hispidulin triggers the ERS pathway through AMPK-mTOR signaling.…”

Section: Discussionmentioning

confidence: 99%

“…More importantly, many in vivo and in vitro studies have demonstrated that hispidulin exerts anti-tumor effects against a variety of solid tumors and hematological malignancies [20][21][22]. Previous studies also evidenced the anti-cancer activities of hispidulin in renal cell carcinoma, acute myeloid leukemia, gallbladder cancer, colorectal cancer, and hepatocellular carcinoma [23][24][25][26][27][28]. In the context of HCC, it has been identified that hispidulin exerts anti-proliferative and pro-apoptotic effects on HepG2 cells [29,30].…”

Section: Introductionmentioning

confidence: 99%

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RETRACTED ARTICLE: Hispidulin induces ER stress-mediated apoptosis in human hepatocellular carcinoma cells in vitro and in vivo by activating AMPK signaling pathway

et al. 2018

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Hispidulin (4',5,7-trihydroxy-6-methoxyflavone) is a phenolic flavonoid isolated from the medicinal plant S. involucrata, which exhibits anti-neoplastic activity against several types of cancer. However, the mechanism underlying its anti-cancer activity against hepatocellular carcinoma (HCC) has not been fully elucidated. In this study, we investigated whether and how hispidulin-induced apoptosis of human HCC cells in vitro and in vivo. We showed that hispidulin (10, 20 μmol/L) dose-dependently inhibited cell growth and promoted apoptosis through mitochondrial apoptosis pathway in human HCC SMMC7721 cells and Huh7 cells. More importantly, we revealed that its pro-apoptotic effects depended on endoplasmic reticulum stress (ERS) and unfolded protein response (UPR), as pretreatment with salubrinal, a selective ERS inhibitor, or shRNA targeting a UPR protein CHOP effectively abrogated hispidulin-induced cell apoptosis. Furthermore, we showed that hispidulin-induced apoptosis was mediated by activation of AMPK/mTOR signaling pathway as pretreatment with Compound C, an AMPK inhibitor, or AMPK-targeting siRNA reversed the pro-apoptotic effect of hispidulin. In HCC xenograft nude mice, administration of hispidulin (25, 50 mg kg d, ip, for 27 days) dose-dependently suppressed the tumor growth, accompanied by inducing ERS and apoptosis in tumor tissue. Taken together, our results demonstrate that hispidulin induces ERS-mediated apoptosis in HCC cells via activating the AMPK/mTOR pathway. This study provides new insights into the anti-tumor activity of hispidulin in HCC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Hispidulin induces ER stress-mediated apoptosis in human hepatocellular carcinoma cells in vitro and in vivo by activating AMPK signaling pathway

et al. 2018

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“…The animal experiments showed that hispidulin administration could suppress tumour growth and lung metastasis. 89 Huangs The activity and intracellular level of PPARγ were increased by them, and the effects can be abolished by a PPARγ inhibitor. 91 The studies on the favourable effects of PPARγ natural agonists for HCC were few, and researches for several other types of cancer are listed in Table 3.…”

Section: Pparγ Natural Agonists In Liver Cancermentioning

confidence: 99%

Therapeutic potential of PPARγ natural agonists in liver diseases

Guo

2020

J Cellular Molecular Medi

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Peroxisome proliferator‐activated receptor gamma (PPARγ) is a vital subtype of the PPAR family. The biological functions are complex and diverse. PPARγ plays a significant role in protecting the liver from inflammation, oxidation, fibrosis, fatty liver and tumours. Natural products are a promising pool for drug discovery, and enormous research effort has been invested in exploring the PPARγ‐activating potential of natural products. In this manuscript, we will review the research progress of PPARγ agonists from natural products in recent years and probe into the application potential and prospects of PPARγ natural agonists in the therapy of various liver diseases, including inflammation, hepatic fibrosis, non‐alcoholic fatty liver and liver cancer.

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“…It seems that AMPK also affects the expression of PPARs. In one study, researchers found that hispidulin increased the expression and transcriptional activation activity of PPAR-γ mediated by AMPK and ERK, not JNK [181]. Therefore, PPAR may be an essential factor in RAS and AMPK, but some studies have confirmed that some ARBs may activate AMPK through the CaMKKβ pathway [182].…”

Section: Pparsmentioning

confidence: 99%

AMPK: a balancer of the renin–angiotensin system

Liu

et al. 2019

Bioscience Reports

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The renin–angiotensin system (RAS) is undisputedly well-studied as one of the oldest and most critical regulators for arterial blood pressure, fluid volume, as well as renal function. In recent studies, RAS has also been implicated in the development of obesity, diabetes, hyperlipidemia, and other diseases, and also involved in the regulation of several signaling pathways such as proliferation, apoptosis and autophagy, and insulin resistance. AMP-activated protein kinase (AMPK), an essential cellular energy sensor, has also been discovered to be involved in these diseases and cellular pathways. This would imply a connection between the RAS and AMPK. Therefore, this review serves to draw attention to the cross-talk between RAS and AMPK, then summering the most recent literature which highlights AMPK as a point of balance between physiological and pathological functions of the RAS.

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RETRACTED: Hispidulin inhibits hepatocellular carcinoma growth and metastasis through AMPK and ERK signaling mediated activation of PPARγ

Cited by 75 publications

References 46 publications

RETRACTED ARTICLE: Hispidulin induces ER stress-mediated apoptosis in human hepatocellular carcinoma cells in vitro and in vivo by activating AMPK signaling pathway

RETRACTED ARTICLE: Hispidulin induces ER stress-mediated apoptosis in human hepatocellular carcinoma cells in vitro and in vivo by activating AMPK signaling pathway

Therapeutic potential of PPARγ natural agonists in liver diseases

AMPK: a balancer of the renin–angiotensin system

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