Gambogenic acid induces G1 arrest via GSK3β-dependent cyclin D1 degradation and triggers autophagy in lung cancer cells

Lei, Yu; Han, Quan‐Bin; Wen, Zhesheng; Ma, Liang; Gao, Jin; Zhou, Guang‐Biao

doi:10.1016/j.canlet.2012.03.004

Cited by 75 publications

(83 citation statements)

References 43 publications

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“…GNA is also able to inhibit cell proliferation, induce cell cycle arrest at G1 phase and suppress colony-forming activity of lung cancer cells (11). Consistent with these previous findings, the present study also demonstrated that GNA was able to inhibit OCM-1 cell growth and induce cell cycle arrest at the G0/G1 phase via repressing the expression of cyclin D1, cyclin E, CDK2 and P21.…”

Section: Discussionsupporting

confidence: 92%

“…Additionally, GNA is able to inhibit cell proliferation in human hepatoma HepG2 cells via inducing cell apoptosis, and may be a possible pharmacological treatment strategy in HepG2 cells (6). GNA is able to induce G1 cell arrest in lung cancer cells via glycogen synthase kinase 3β-dependent cyclin D1 degradation and may have therapeutic potential in the treatment of lung cancer (11). GNA has also been demonstrated to serve a role in the apoptosis of U251 glioblastoma cells through inactivation of the protein kinase B (Akt) pathway (12).…”

Section: Introductionmentioning

confidence: 99%

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Gambogenic acid induces cell growth inhibition, cell cycle arrest and metastasis inhibition in choroidal melanoma in a dose-dependent manner

Wang

Yan

2017

Experimental and Therapeutic Medicine

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Abstract. The aim of the present study was to explore the effects of gambogenic acid (GNA) on the malignant behaviors of choroidal melanoma cells, including cell viability, cell cycle, migration and invasion, and to elucidate the underlying regulatory mechanism. The human choroidal melanoma cell line OCM-1 was treated with different concentrations of GNA and cell viability, colony formation ability, cell cycle, migration and invasion were analyzed. Additionally, cells were incubated with or without LY294002, a specific inhibitor of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, for 24 h. Levels of cell cycle-associated proteins (cyclin D1, cyclin E, cyclin-dependent kinase 2 and P21), epithelial-mesenchymal transition (EMT)-associated molecules (epithelial-cadherin, α-smooth muscle actin and vimentin) and phosphorylated (p)-AKT/AKT were determined using reverse transcription-quantitative polymerase chain reaction and western blot analysis. The results demonstrated that GNA significantly inhibited cell viability and induced cell cycle arrest at the G0/G1 phase in a dose-dependent manner (P<0.01). Furthermore, GNA administration significantly suppressed cell migration and invasion in a dose-dependent manner (P<0.01). Treatment with GNA or LY294002 induced a marked decrease in the expression of p-AKT/AKT, a significant downregulation in cell cycle-associated molecules (P<0.01), and a significant decrease in cell viability (P<0.01). Co-treatment with LY294002 and GNA had an additive effect on the growth of OCM-1 cells. In conclusion, the results of the present study suggest that treatment with GNA may inhibit cell viability and induce G0/G1 arrest. Furthermore, GNA may also inhibit cell metastasis via regulating EMT-associated molecules. The PI3K/Akt signaling pathway may be a key mechanism involved in the progression of choroidal melanoma, and GNA may serve as a potential therapeutic reagent for the treatment of this disease.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Gambogenic acid induces cell growth inhibition, cell cycle arrest and metastasis inhibition in choroidal melanoma in a dose-dependent manner

Wang

Yan

2017

Experimental and Therapeutic Medicine

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“…16 Previous studies have shown that gamboges have therapeutic effects on breast and skin cancer and pancreatic adenocarcinoma; 17 the chemotherapeutic agent neogambogic acid (NGA), an active component of gamboges, demonstrates antitumor potential in vitro and in vivo. [18][19][20] NGA increased the death of S180-Lewis lung cancer, CNE-1 human nasopharyngeal carcinoma, and ascites carcinoma cells in a dose-dependent manner. 21 In the present study, we synthesized CNPs modified with NGA (NGA-CNPs) for increased toxicity and targeting, and NGA-CNPs were tested for their ability to enhance the effectiveness of radiation in killing cancer cells.…”

Section: Introductionmentioning

confidence: 92%

“…20,29 To determine whether NGA, CNPs, or NGA-CNPs increase cellular sensitivity to radiation, breast cancer cell growth upon exposure to both was evaluated with the clonogenic assay. MCF-7 cells were exposed to three different concentrations of NGA (0 μg/mL, 0.5 μg/mL, or 1 μg/mL), CNP (0 μg/mL, 10 μg/mL, or 20 μg/mL), or NGA-CNP (0 μg/mL, 10 μg/mL, or 20 μg/mL) for 24 hours prior to irradiation at one of five doses (0 Gy, 2 Gy, 4 Gy, 6 Gy, or 8 Gy).…”

Section: Nga-cnps Enhance Radiation-induced Growth Inhibitionmentioning

confidence: 99%

Enhancement of radiotherapy by ceria nanoparticles modified with neogambogic acid in breast cancer cells

Chen¹,

Zhang²,

Hu³

et al. 2015

IJN

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Radiotherapy is one of the main strategies for cancer treatment but has significant challenges, such as cancer cell resistance and radiation damage to normal tissue. Radiosensitizers that selectively increase the susceptibility of cancer cells to radiation can enhance the effectiveness of radiotherapy. We report here the development of a novel radiosensitizer consisting of monodispersed ceria nanoparticles (CNPs) covered with the anticancer drug neogambogic acid (NGA-CNPs). These were used in conjunction with radiation in MCF-7 breast cancer cells, and the efficacy and mechanisms of action of this combined treatment approach were evaluated. NGA-CNPs potentiated the toxic effects of radiation, leading to a higher rate of cell death than either treatment used alone and inducing the activation of autophagy and cell cycle arrest at the G2/M phase, while pretreatment with NGA or CNPs did not improve the rate of radiation-induced cancer cells death. However, NGA-CNPs decreased both endogenous and radiation-induced reactive oxygen species formation, unlike other nanomaterials. These results suggest that the adjunctive use of NGA-CNPs can increase the effectiveness of radiotherapy in breast cancer treatment by lowering the radiation doses required to kill cancer cells and thereby minimizing collateral damage to healthy adjacent tissue.

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“…1A. It has potent anticancer activity via targeting various intracellular signaling pathways associated with G1/S arrest, cell apoptosis, and autophagy [17][18][19][20][21]. However, the anti-inflammatory activity of GEA has not yet been clearly defined.…”

Section: Introductionmentioning

confidence: 99%

Gambogenic acid inhibits LPS-simulated inflammatory response by suppressing NF-κB and MAPK in macrophages

Lei¹,

Zhao²,

Zhang³

et al. 2016

ABBS

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Inflammation is a response of body tissues to injury and infection. Compounds that can inhibit inflammation have been shown to have potential therapeutic clinical application. Gambogenic acid (GEA) has potent antitumor and anti-inflammatory activities. Herein, the molecular mechanisms of GEA's anti-inflammatory effect were investigated in lipopolysaccharide (LPS)-stimulated macrophage cells. The results showed that pretreatment with GEA could markedly inhibit interleukin (IL)-1α, IL-1β, tumor necrosis factor-α, IFN-β, IL-12b, and IL-23a production in a dose-dependent manner in LPS-induced model. Furthermore, this drug significantly reduced the release of nitric oxide (NO), and impaired the protein level of inducible NO synthase and the cyclooxygenase 2. The finding also showed that the effect of GEA may be related to the suppression of the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathway. These results indicate that GEA could suppress LPS-simulated inflammatory response partially by attenuating NO synthesis and NF-κB and MAPK activation, suggesting that it may become a potent therapeutic agent for the treatment of inflammatory diseases.

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Gambogenic acid induces G1 arrest via GSK3β-dependent cyclin D1 degradation and triggers autophagy in lung cancer cells

Cited by 75 publications

References 43 publications

Gambogenic acid induces cell growth inhibition, cell cycle arrest and metastasis inhibition in choroidal melanoma in a dose-dependent manner

Gambogenic acid induces cell growth inhibition, cell cycle arrest and metastasis inhibition in choroidal melanoma in a dose-dependent manner

Enhancement of radiotherapy by ceria nanoparticles modified with neogambogic acid in breast cancer cells

Gambogenic acid inhibits LPS-simulated inflammatory response by suppressing NF-κB and MAPK in macrophages

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Gambogenic acid induces G1 arrest via GSK3β-dependent cyclin D1 degradation and triggers autophagy in lung cancer cells

Cited by 75 publications

References 43 publications

Gambogenic acid induces cell growth inhibition, cell cycle arrest and metastasis inhibition in choroidal melanoma in a dose-dependent manner

Gambogenic acid induces cell growth inhibition, cell cycle arrest and metastasis inhibition in choroidal melanoma in a dose-dependent manner

Enhancement of radiotherapy by ceria nanoparticles modified with neogambogic acid in&nbsp;breast cancer cells

Gambogenic acid inhibits LPS-simulated inflammatory response by suppressing NF-&kappa;B and MAPK in macrophages

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Enhancement of radiotherapy by ceria nanoparticles modified with neogambogic acid in breast cancer cells

Gambogenic acid inhibits LPS-simulated inflammatory response by suppressing NF-κB and MAPK in macrophages