Ganoderic acid, lanostanoid triterpene: a key player in apoptosis

Gill, Balraj Singh; Navgeet,; Mehra, Richa; Kumar, Vicky; Kumar, Sanjeev

doi:10.1007/s10637-017-0526-0

Cited by 26 publications

(9 citation statements)

References 57 publications

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“…Cyclin D1 is a downstream molecule of the PI3K/AKT pathway, and its overexpression has been linked to the development and progression of cancer . GA‐A has been reported to induce apoptosis in cancer cells through modulation of the PI3K/AKT pathway . In our study, the expression levels of phosphorylated AKT, mTOR, P70S6K, and cyclin D1 were significantly decreased after GA‐A treatment.…”

Section: Discussionsupporting

confidence: 52%

Ganoderic acid A holds promising cytotoxicity on human glioblastoma mediated by incurring apoptosis and autophagy and inactivating PI3K/AKT signaling pathway

Cheng

Xie

2019

J Biochem & Molecular Tox

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Ganoderic acid A (GA-A), recognized as a lanostanetriterpene isolated fromGanoderma lucidum, demonstrates an efficient antitumor activity in multiple cancers.To date, it is unclear whether and how GA-A functions on human glioblastoma (GBM).To unravel the functional significance of GA-A on human glioblastoma (GBM), the cell-counting kit-8 and transwell assays were used to detect proliferation, migration, and invasion of human GBM cell after GA-A treatment. Then, we utilized the flow cytometry and western blot to further evaluate the effect of GA-A on GBM cell.Further, activities of autophagy and PI3K/AKT signaling were assessed by Western blot assay. We found that GA-A significantly inhibited proliferation, migration, and invasion of GBM cell. Additionally, GA-A markedly triggered cell apoptosis, which incarnated an elevation trend in apoptotic percentage, simultaneously, an increased level of proapoptosis protein (Bax and active caspase-3) and a decreased level of antiapoptosis protein (Bcl-2), induced by GA-A treatment. Meanwhile, levels of two well-known autophagy markers (beclin 1 and LC3 II) increased while another autophagic substrate (P-62) was reduced. Moreover, the expressions levels of phosphorylated AKT, mTOR, p-P70S6K, and cyclin D1 in the PI3K/AKT pathway were significantly reduced, which revealed GA-A repressed the activation of PI3K/AKT signaling pathway. Collectively, these results indicate that GA-A may encourage U251 cell growth and invasion/migration inhibition, apoptosis, and autophagy through the inactivation of PI3K/AKT signaling pathway in human GBM. Hence, GA-A may be a potent antitumorigenic agent for human GBM in future clinical practice.

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Section: Discussionsupporting

confidence: 52%

Ganoderic acid A holds promising cytotoxicity on human glioblastoma mediated by incurring apoptosis and autophagy and inactivating PI3K/AKT signaling pathway

Cheng

Xie

2019

J Biochem & Molecular Tox

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“…Therefore, we concluded that GAA might alleviate hypoxia‐induced growth arrest and apoptosis through activating the PI3K/AKT pathway. Unlike the effects on NSCs, GAA suppresses proliferation and viability and induces apoptosis in cancer cells through either intracellular or extracellular pathway (Gill, Navgeet, Mehra, Kumar, & Kumar, ). The different downstream proteins and adapter molecules of GAA in stressed cells and cancer cells might explain the opposite effects of GAA on viability and apoptosis, which needs more experiments in the future.…”

Section: Discussionmentioning

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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“…Two major active components are responsible: G. lucidum polysaccharides and G. lucidum triterpenoids (GTs) [ 15 ]. As one of the most abundant GTs, ganoderic acids (GAs) have anti-inflammatory, anti-oxidative stress, anti-tumor and anti-apoptotic effects [ 16 , 17 , 18 , 19 ]. It has been reported that Ganoderic Acid F, one component of GAs, can suppress LPS-induced the activation of NF-kB pathway and inhibit LPS-triggered iNOS expression and the production and secretion of relative inflammatory cytokines in mice [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Ganoderic Acids Prevent Renal Ischemia Reperfusion Injury by Inhibiting Inflammation and Apoptosis

Shao

Meng

et al. 2021

IJMS

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Renal ischemia reperfusion injury (RIRI) is one of the main causes of acute kidney injury (AKI), which can lead to acute renal failure. The development of RIRI is so complicated that it involves many factors such as inflammatory response, oxidative stress and cell apoptosis. Ganoderic acids (GAs), as one of the main pharmacological components of Ganoderma lucidum, have been reported to possess anti-inflammatory, antioxidant, and other pharmacological effects. The study is aimed to investigate the protective effect of GAs on RIRI and explore related underlying mechanisms. The mechanisms involved were assessed by a mouse RIRI model and a hypoxia/reoxygenation model. Compared with sham-operated group, renal dysfunction and morphological damages were relieved markedly in GAs-pretreatment group. GAs pretreatment could reduce the production of pro-inflammatory factors such as IL-6, COX-2 and iNOS induced by RIRI through inhibiting TLR4/MyD88/NF-kB signaling pathway. Furthermore, GAs reduced cell apoptosis via the decrease of the ratios of cleaved caspase-8 and cleaved caspase-3. The experimental results suggest that GAs prevent RIRI by alleviating tissue inflammation and apoptosis and might be developed as a candidate drug for preventing RIRI-induced AKI.

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Ganoderic acid, lanostanoid triterpene: a key player in apoptosis

Cited by 26 publications

References 57 publications

Ganoderic acid A holds promising cytotoxicity on human glioblastoma mediated by incurring apoptosis and autophagy and inactivating PI3K/AKT signaling pathway

Ganoderic acid A holds promising cytotoxicity on human glioblastoma mediated by incurring apoptosis and autophagy and inactivating PI3K/AKT signaling pathway

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

Ganoderic Acids Prevent Renal Ischemia Reperfusion Injury by Inhibiting Inflammation and Apoptosis

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