Ganoderic acid A inhibits proliferation and invasion, and promotes apoptosis in human hepatocellular carcinoma cells

Wang, Xu; Sun, Di; Tai, Jiandong; Wang, Lei

doi:10.3892/mmr.2017.7048

Cited by 34 publications

(25 citation statements)

References 31 publications

(35 reference statements)

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“…As the key ingredient of G. lucidum, GAA has been studied in different kinds of illnesses (Chi et al, 2018;Jiang et al, 2018). One research attested that GAA could prohibit hepatocellular carcinoma cells survival and invasion (Wang, Sun, et al, 2017). Other recent literature disclosed that GAA could assuage hypoxia-provoked rat neural stem cells apoptosis, autophagy, and inflammation via mediation of PI3K/AKT and mTOR pathways (Chang & Kong, 2019).…”

Section: Discussionmentioning

confidence: 99%

Retracted: Ganoderic Acid A exerts the cytoprotection against hypoxia‐triggered impairment in PC12 cells via elevating microRNA‐153

Lou

Zhang

et al. 2019

Phytotherapy Research

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Ganoderic Acid A (GAA) is often applied for healing cardiovascular and cerebrovascular ailments, but the influences in cerebral ischemia injury are still hazy. The research delved into the functions of GAA in hypoxia‐triggered impairment in PC12 cells. PC12 cells received hypoxia management for 12 hr, and subsequently, cell viability, migration, apoptosis, and correlative protein levels were assessed. After preprocessing with GAA, above cell behaviors were monitored again. The vector of microRNA (miR)‐153 inhibitor was utilized for PC12 cell transfection to further explore the functions of miR‐153 in hypoxia‐impaired cells. Pathways of phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (AKT) and mammalian target of rapamycin (mTOR) were investigated via executing western blot for uncovering the latent mechanism. Results revealed that hypoxia disposition triggered PC12 cells impairment via restraining cell viability and migration and accelerating apoptosis. However, GAA visibly mollified hypoxia‐provoked impairment in PC12 cells. Interestingly, the enhancement of miR‐153 triggered by GAA was observed in hypoxia‐impaired PC12 cells. After miR‐153 inhibitor transfection, the protective functions of GAA in hypoxia‐impaired PC12 cells were dramatically inversed. Furthermore, GAA caused PI3K/AKT and mTOR activations via enhancement of miR‐153 in hypoxia‐impaired PC12 cells. The findings evinced that GAA exhibited the protective functions in PC12 cells against hypoxia‐evoked impairment through activating PI3K/AKT and mTOR via elevating miR‐153.

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Section: Discussionmentioning

confidence: 99%

Retracted: Ganoderic Acid A exerts the cytoprotection against hypoxia‐triggered impairment in PC12 cells via elevating microRNA‐153

Lou

Zhang

et al. 2019

Phytotherapy Research

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“…Ganoderic acid A (GAA), isolated from G. lucidum , is a highly oxygenated C30 lanostane triterpene exhibiting various biological activities. For example, GAA showed an antitumor effects on human hepatocellular carcinoma cells as cell proliferation and invasion were repressed, whereas apoptosis was enhanced after GAA treatments (Wang, Sun, Tai, & Wang, ). The inhibitory effects of GAA on CDK4 expression, secretion of urokinase plasminogen activator, and farnesyl protein transferase were well documented previously (Tawasri, Ampasavate, Tharatha, Chiranthanut, & Teekachunhatean, ).…”

Section: Introductionmentioning

confidence: 99%

Retracted: Ganoderic acid A alleviates hypoxia‐induced apoptosis, autophagy, and inflammation in rat neural stem cells through the PI3K/AKT/mTOR pathways

Chang

Kong

2019

Phytotherapy Research

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Effects of ganoderic acid A (GAA), a lanostane triterpene, on hypoxia‐ischemia encephalopathy (HIE) remain unclear. We aimed to figure out the specific role of GAA in hypoxia‐treated neural stem cells (NSCs) as well as the regulatory mechanisms. Primary rat NSCs were incubated under hypoxia to simulate HIE. Viability and apoptosis of hypoxia‐injured NSCs were measured by cell counting kit‐8 and flow cytometry assays, respectively. Proteins related to apoptosis, autophagy, and the PI3K/AKT/mTOR pathways were evaluated by Western blot analysis. LY294002 and rapamycin were added to inhibit the PI3K/AKT pathway and mTOR pathway, respectively. Enzyme‐linked immunosorbent assay was carried out to test the release of proinflammatory cytokines. We found that hypoxia‐induced decrease of cell viability, increases of apoptotic cells and autophagy, and the release of IL‐6, IL‐1β, and TNF‐α were all attenuated by GAA stimulation. Activation of caspases induced by hypoxia was alleviated by GAA. Furthermore, we found that inhibition of the PI3K/AKT pathway eliminated the effects of GAA on apoptosis and proinflammatory cytokines release in hypoxia‐injured NSCs. Meanwhile, inhibition of the mTOR pathway abrogated the effects of GAA on cell autophagy in hypoxia‐injured NSCs. In conclusion, GAA alleviated hypoxia‐induced injury in NSCs might be through activating the PI3K/AKT and mTOR pathways.

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“…Ling Zhi has also been used to prevent and treat various human diseases, and the main part of its extract ganoderic acid A (GAA), plays a vital role during the treatment. GAA has an inhibitory effect on the proliferation and invasion of hepatocellular carcinoma cells, and induce its apoptosis (Wang et al 2017). GAA also has positive effect on the lung injury induced by lipopolysaccharide (Wan et al 2019).…”

Section: Introductionmentioning

confidence: 98%

In vitroinhibitory effects of ganoderic acid A on human liver cytochrome P450 enzymes

Zhang²,

Chen

et al. 2020

Pharmaceutical Biology

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Context: Ganoderic acid A (GAA) is usually used to prevent cancers or other diseases, which make it likely to be used with other drugs metabolized by cytochromes P450. Objective: This study investigates the effect of GAA on eight major cytochrome P450 isoforms in human liver microsomes. Material and method: The effects of GAA (100 lM) on eight human liver CYP isoforms (i.e., 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19, and 2C8) were investigated in vitro using human liver microsomes (HLMs) with specific substrates for the CYPs, and the enzyme kinetic parameters were calculated. Results: The results showed that GAA inhibited the activity of CYP3A4, 2D6, and 2E1, but did not affect other isoforms. The inhibition of CYP3A4, 2D6, and 2E1 was concentration-dependent with IC 50 values of 15.05, 21.83, and 28.35 lM, respectively. Additionally, GAA was not only a non-competitive inhibitor of CYP3A4, but also a competitive inhibitor of CYP2D6 and 2E1, with Ki values of 7.16, 10.07, and 13.45 lM. Meanwhile, the inhibition of CYP3A4 was time-dependent, with the K I /K inact value of 7.91/0.048 lM/min. Discussion and conclusion: The in vitro study indicated that GAA has the potential to result in drugdrug interactions with other drugs metabolized by CYP3A4, 2D6, and 2E1. Further clinical studies are needed for the identification of this interaction.

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Ganoderic acid A inhibits proliferation and invasion, and promotes apoptosis in human hepatocellular carcinoma cells

Cited by 34 publications

References 31 publications

Retracted: Ganoderic Acid A exerts the cytoprotection against hypoxia‐triggered impairment in PC12 cells via elevating microRNA‐153

Retracted: Ganoderic Acid A exerts the cytoprotection against hypoxia‐triggered impairment in PC12 cells via elevating microRNA‐153

Retracted: Ganoderic acid A alleviates hypoxia‐induced apoptosis, autophagy, and inflammation in rat neural stem cells through the PI3K/AKT/mTOR pathways

In vitroinhibitory effects of ganoderic acid A on human liver cytochrome P450 enzymes

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