Oenothein B inhibits human non-small cell lung cancer A549 cell proliferation by ROS-mediated PI3K/Akt/NF-κB signaling pathway

Pei, Xiao-Dong; Xiao, Junsong; Wei, Guijiang; Zhang, Yumeng; Lin, Feng; Xiong, Zhengfang; Lü, Lei; Wang, Xueli; Pang, Guangfu; Jiang, Yan; Jiang, Lufang

doi:10.1016/j.cbi.2018.09.021

Cited by 39 publications

(32 citation statements)

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“…Madrid et al (2000) verified that Akt could inhibit apoptosis through activating NF-kB p65. Therefore, PI3K/Akt/NF-kB signaling pathway is very important in cell proliferation and tumor progression, and its inhibition may affect cancer cells proliferation and viability (Ni and Yi, 2017;Yu et al, 2017;Pei et al, 2019). Gu et al (2018) found that GA significantly induced apoptosis of acute myeloid leukemiacell lines (AML), primary mononuclear cells (MNC) and CD34 stem/progenitors isolated form AML patients via Akt/ mTOR dependent mitochondrial respiration inhibition, and mitochondrial respiratory inhibition was the result of Akt/ mTOR signal inhibition.…”

Section: Introductionmentioning

confidence: 99%

Gallic Acid Inhibits Bladder Cancer T24 Cell Progression Through Mitochondrial Dysfunction and PI3K/Akt/NF-κB Signaling Suppression

Zeng

et al. 2020

Front. Pharmacol.

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Gallic acid (GA), a hydrolyzable tannin, has a wide range of pharmacological activities. This study revealed that, GA significantly inhibited T24 cells viability in a concentration-and time-dependent manner. The IC 50 of GA stimulating T24 cells for 24, 48, and 72 h were 21.73, 18.62, and 11.59 µg/ml respectively, and the inhibition rate was significantly higher than the positive control drug selected for CCK-8 assay. Meanwhile, after GA treatment, the morphology of T24 cells were changed significantly. Moreover, GA significantly inhibited T24 cells proliferation and blocked T24 cells cycle in S phase (p < 0.001). GA induced T24 cells apoptosis (p < 0.001), accompanied by reactive oxygen species (ROS) accumulation and mitochondrial membrane potential (MMP) depolarization. Western blotting analysis showed that GA significantly increased Cleaved caspase-3, Bax, P53, and Cytochrome C (Cyt-c) proteins expression, and decreased Bcl-2, P-PI3K, P-Akt, P-IkBa, P-IKKa, and P-NF-kB p65 proteins expression in T24 cells (p < 0.05). Real-Time PCR results verified that GA significantly promoted Caspase-3, Bax, P53, and Cyt-c genes expression, and inhibited Bcl-2, PI3K, Akt, and NF-kB p65 genes expression (p < 0.001). However, on the basis of GA (IC 50) stimulation, NAC (an oxidative stress inhibitor) pretreatment reversed the apoptotic rate of T24 cells and the expression of Bax, Cleaved caspase-3, P53, Bcl-2 proteins, and the MMP level in T24 cells, as well as the expression of Cyt-c protein in T24 cells mitochondria and cytoplasm. In addition, GA significantly suppressed T24 cells migration and invasion ability with VEGF protein inhibition (p < 0.001). Briefly, GA can inhibit T24 cells proliferation, metastasis and promote apoptosis, and the pro-apoptotic activity is closely associated with mitochondrial dysfunction and PI3K/Akt/NF-kB signaling suppression. Our study will help in finding a safe and effective treatment for bladder cancer.

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Section: Introductionmentioning

confidence: 99%

Gallic Acid Inhibits Bladder Cancer T24 Cell Progression Through Mitochondrial Dysfunction and PI3K/Akt/NF-κB Signaling Suppression

Zeng

et al. 2020

Front. Pharmacol.

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“…Various studies have proposed that apoptosis deregulation influences the balancing between cell proliferation and cell death, contributing to cell growth [5]. Besides, growth factors and cytokines, especially nuclear factor kappa B (NF-κB), promote the generation of reactive oxygen species (ROS) in the cytotoxicity and development of cancer [6].…”

Section: Introductionmentioning

confidence: 99%

Zerumbone Promotes Cytotoxicity in Human Malignant Glioblastoma Cells through Reactive Oxygen Species (ROS) Generation

Jalili‐Nik

Sadeghi

Mohtashami

et al. 2020

Oxidative Medicine and Cellular Longevity

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Glioblastoma multiforme (GBM) is the most hostile tumor in the central nervous system. Unfortunately, the prognosis of GBM patients is poor following surgical interventions, chemotherapy, and radiotherapy. Consequently, more efficient and effective treatment options for the treatment of GBM need to be explored. Zerumbone, as a sesquiterpene derived from Zingiber zerumbet Smith, has substantial cytotoxic and antiproliferative activities in some types of cancer. Here, we show that exposure of GBM cells (U-87 MG) to Zerumbone demonstrated significant growth inhibition in a concentration-dependent manner. Zerumbone also induced apoptosis and caused cell cycle arrest of human GBM U-87 MG cells in the G2/M phase of the cell cycle. In detail, the apoptotic process triggered by Zerumbone involved the upregulation of proapoptotic Bax and the suppression of antiapoptotic Bcl-2 genes expression as determined by qRT-PCR. Moreover, Zerumbone enhanced the generation of reactive oxygen species (ROS), and N-acetyl cysteine (NAC), as an antioxidant, reversed the ROS-induced cytotoxicity of U-87 MG cells. The Western blot analysis suggested that Zerumbone activated the NF-κB p65, which was partly inhibited by NAC treatment. Collectively, our results confirmed that Zerumbone induces cytotoxicity by ROS generation. Thus, the study raises the possibility of Zerumbone as a potential natural agent for treating GBM due to its ability to induce cytotoxicity.

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“…ROS-induced apoptosis was proved to be largely associated with inhibition of PI3K-Akt signaling pathway [38]. Multiple cytotoxic agents exert pharmacological activities through ROS-mediated inhibition of PI3K-Akt signaling pathway [58][59][60][61].…”

Section: Discussionmentioning

confidence: 99%

18β-Glycyrrhetinic acid induces human HaCaT keratinocytes apoptosis through ROS-mediated PI3K-Akt signaling pathway and ameliorates IMQ-induced psoriasis-like skin lesions in mice

Gao

Guo

Nong

et al. 2020

BMC Pharmacol Toxicol

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Background: Psoriasis is a chronic inflammatory skin disease affecting 2-3% of the population worldwide. Hyperproliferative keratinocytes were thought to be an amplifier of inflammatory response, thereby sustaining persistence of psoriasis lesions. Agents with the ability to inhibit keratinocyte proliferation or induce apoptosis are potentially useful for psoriasis treatment. 18β-Glycyrrhetinic acid (GA), an active metabolite of glycyrrhizin, exhibits diverse pharmacological activities, including anti-inflammatory, anti-bacteria and anti-proliferation. The current study aims to evaluate the effects of GA on the proliferation and apoptosis of human HaCaT keratinocytes in vitro and investigate the effects of GA on the skin lesions of imiquimod (IMQ)-induced psoriasis-like mouse model in vivo. Methods: Cell viability was assayed by CCK-8. Flow cytometry was performed to measure apoptosis and reactive oxygen species (ROS), with Annexin V-FITC/PI detection kit and DCFH-DA probe respectively. Caspase 9/3 activities were measured using caspase activity assay kits. The protein levels of Akt and p-Akt were determined using Western blotting. IMQ was applied to induce psoriasis-like skin lesions in mice. The histological change in mouse skin lesions was detected using hematoxylin and eosin (H&E) staining. The severity of skin lesions was scored based on Psoriasis Area Severity Index (PASI). RT-PCR was employed to examine the relative expression of TNF-α, IL-22 and IL-17A in mouse skin lesions. Results: GA decreased HaCaT keratinocytes viability and induced cell apoptosis in a dose-dependent manner. In the presence of GA, intracellular ROS levels were significantly elevated. NAC, a ROS inhibitor, attenuated GAmediated HaCaT keratinocytes growth inhibition and apoptosis. In addition, GA treatment remarkably decreased p-Akt protein level, which could be restored partially when cells were co-treated with GA and NAC. LY294002 (a PI3K inhibitor) treatment significantly enhanced GA-mediated cytotoxicity. Moreover, GA ameliorated IMQ-induced psoriasis-like skin lesions in mice. Conclusions: GA inhibits proliferation and induces apoptosis in HaCaT keratinocytes through ROS-mediated inhibition of PI3K-Akt signaling pathway, and ameliorates IMQ-induced psoriasis-like skin lesions in mice.

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Oenothein B inhibits human non-small cell lung cancer A549 cell proliferation by ROS-mediated PI3K/Akt/NF-κB signaling pathway

Cited by 39 publications

References 32 publications

Gallic Acid Inhibits Bladder Cancer T24 Cell Progression Through Mitochondrial Dysfunction and PI3K/Akt/NF-κB Signaling Suppression

Gallic Acid Inhibits Bladder Cancer T24 Cell Progression Through Mitochondrial Dysfunction and PI3K/Akt/NF-κB Signaling Suppression

Zerumbone Promotes Cytotoxicity in Human Malignant Glioblastoma Cells through Reactive Oxygen Species (ROS) Generation

18β-Glycyrrhetinic acid induces human HaCaT keratinocytes apoptosis through ROS-mediated PI3K-Akt signaling pathway and ameliorates IMQ-induced psoriasis-like skin lesions in mice

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Oenothein B inhibits human non-small cell lung cancer A549 cell proliferation by ROS-mediated PI3K/Akt/NF-κB signaling pathway

Cited by 39 publications

References 32 publications

Gallic Acid Inhibits Bladder Cancer T24 Cell Progression Through Mitochondrial Dysfunction and PI3K/Akt/NF-κB Signaling Suppression

Gallic Acid Inhibits Bladder Cancer T24 Cell Progression Through Mitochondrial Dysfunction and PI3K/Akt/NF-κB Signaling Suppression

Zerumbone Promotes Cytotoxicity in Human Malignant Glioblastoma Cells through Reactive Oxygen Species (ROS) Generation

18β-Glycyrrhetinic acid induces human HaCaT keratinocytes apoptosis through ROS-mediated PI3K-Akt signaling pathway and ameliorates IMQ-induced psoriasis-like skin lesions in mice

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Oenothein B inhibits human non-small cell lung cancer A549 cell proliferation by ROS-mediated PI3K/Akt/NF-κB signaling pathway