Aloin promotes A549 cell apoptosis via the reactive oxygen species-mitogen activated protein kinase signaling pathway and p53 phosphorylation

Wan, Li; Zhang, Lin; Fan, Kai; Wang, Jianjun

doi:10.3892/mmr.2017.7379

Cited by 38 publications

(25 citation statements)

References 56 publications

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“…It has been reported to have anti-inflammatory, 1,2 anti-oxidant, 3 and anti-tumour effects. 4,5 In addition, ALO has been reported to inhibit proliferation and induce the apoptosis of various tumour cells. 1,5,6 However, the molecular mechanism(s) underlying ALO's anti-cancer activity remain to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

<p>Aloin Inhibits the Proliferation and Migration of Gastric Cancer Cells by Regulating NOX2–ROS-Mediated Pro-Survival Signal Pathways</p>

Wang¹,

Tang²,

Wang³

et al. 2020

DDDT

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Background: Aloin has been reported to have many pharmacological effects including antiinflammatory, anti-oxidant and anti-tumour activities. However, the precise molecular mechanisms underlying the anti-tumour properties of aloin are yet to be elucidated. Methods: HGC-27 and BGC-823 gastric cancer cells were treated with aloin. EdU and colony formation assays were used to detect the proliferation ability of cells. The migration of cells was detected using wound healing and transwell assays. Western blotting was used to detect the levels of cyclinD1, cyclin E1, MMPs, N-cadherin, E-cadherin and NOX2. The phosphorylation of Akt, mTOR, P70S6K, S6, Src, stat3 and IκBα were also detected by Western blotting. Flow cytometry was used to detect the cell cycle distribution.The location of p65 in cells was determined by using a confocal microscopy assay. The total amounts of ROS present in cells were measured using an ROS assay kit. Results: Here, we found that aloin inhibited the proliferation and migration of HGC-27 and BGC-823 gastric cancer cells using a combination of EdU, colony formation, wound healing and transwell assays. Further investigations revealed that aloin decreased the protein expression levels of cyclin D1, N-cadherin, and the matrix metalloproteinases (MMP)-2 and MMP-9; increased E-cadherin expression in a dose-dependent manner; inhibited reactive oxygen species (ROS) generation; and mediated the activation of Akt-mTOR, signal transducer and activator of transcription-3 (Stat3), and NF-κB signalling pathways. Our results also indicated that aloin is able to attenuate the expression levels of the two regulatory proteins of nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2), p47 phox and p22 phox , but had no effect on the level of gp91 phox. N-acetylcysteine treatment of gastric cancer cells inhibited ROS production and Akt-mTOR, Stat3, and IκBα phosphorylation. Taken together, our data suggest that aloin inhibits the proliferation and migration of gastric cancer cells by downregulating NOX2-ROS-mediated activation of the Akt-mTOR, Stat3, and NF-κB signalling pathways. Conclusion: Our findings suggest a potential role for aloin in the prevention of gastric cancer cell proliferation and migration and provide novel insights into the anti-cancer properties of aloin.

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Section: Introductionmentioning

confidence: 99%

<p>Aloin Inhibits the Proliferation and Migration of Gastric Cancer Cells by Regulating NOX2–ROS-Mediated Pro-Survival Signal Pathways</p>

Wang¹,

Tang²,

Wang³

et al. 2020

DDDT

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“…The Aloe vera plant has been widely used in health and nutritional supplements in Chinese herbal medicine ( 12 ). Aloin, a bioactive ingredient extracted from Aloe vera , has been indicated to induce anti-inflammatory ( 13 ), antioxidan ( 12 ) and antitumour ( 14 - 16 ) effects, neuroprotection ( 17 ) and osteoclastogenesis ( 18 , 19 ). However, the anti-inflammatory mechanism of aloin remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Aloin suppresses lipopolysaccharide‑induced inflammation by inhibiting JAK1‑STAT1/3 activation and ROS production in RAW264.7 cells

Tang

Sheng

et al. 2018

Int J Mol Med

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The anti-inflammatory effects of aloin, a bioactive ingredient extracted from Aloe vera, have been described previously. The present study aimed to assess these effects and explore the underlying molecular mechanisms. RAW264.7 cells were incubated with different doses of aloin (100, 150 and 200 µg/ml) and lipopolysaccharide (LPS; 100 ng/ml) for the indicated times. Then, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 expression levels were detected by western blot analysis and reverse transcription polymerase chain reaction (RT-PCR). The concentrations of inflammatory cytokines in the cell culture supernatant were determined by ELISA. Total nitric oxide (NO) assay and reactive oxygen species (ROS) kits were used to detect NO and ROS levels, respectively. Mitogen-activated protein kinase, nuclear factor κB and Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway activation were verified by western blot analysis. Confocal and nucleocytoplasmic separation experiments were used to detect STAT nuclear translocation. It was identified that aloin decreased the level of LPS-induced iNOS expression, inhibiting the release of interleukin (IL)-1β, IL-6, tumour necrosis factor-α and NO dose-dependently. Mechanistically, aloin suppressed LPS-induced JAK1-STAT1/3 activation and STAT1/3 nuclear translocation. Additionally, LPS-induced ROS production was inhibited by aloin. Collectively, these data suggest that aloin attenuated LPS-induced inflammation by inhibiting ROS-mediated activation of the JAK1-STAT1/3 signalling pathway, thereby inhibiting the nuclear translocation of STAT1/3 in RAW264.7 cells. The present study provides an experimental basis for the clinical application of aloin in inflammatory-associated diseases.

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“…Several lines of evidence demonstrate that aloin exhibits anti-oxidative and anti-inflammatory activities in rats and murine macrophages [ 14 , 15 , 16 , 17 , 18 ]. Aloin also shows a pronounced anti-proliferative effect, the treatment of aloin-induced cell cycle arrest, and apoptotic cell death in several human cancer cell lines [ 19 , 20 , 21 , 22 ]. Moreover, a cell line-derived xenograft mouse model indicates that aloin inhibits tumor angiogenesis and growth via blocking STAT3 activation [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

Aloin Suppresses Lipopolysaccharide-Induced Inflammatory Response and Apoptosis by Inhibiting the Activation of NF-κB

et al. 2018

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Numerous herbal-derived natural products are excellent anti-inflammatory agents. Several studies have reported that aloin, the major anthraquinone glycoside obtained from the Aloe species, exhibits anti-inflammatory activity. However, the molecular mechanism of this activity is not well understood. In this report, we found that aloin suppresses lipopolysaccharide-induced pro-inflammatory cytokine secretion and nitric oxide production, and downregulates the expression of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). Aloin inhibits the phosphorylation and acetylation of the NF-κB p65 subunit by suppressing the upstream kinases p38 and Msk1, preventing LPS-induced p65 translocation to the nucleus. We have also shown that aloin inhibits LPS-induced caspase-3 activation and apoptotic cell death. Collectively, these findings suggest that aloin effectively suppresses the inflammatory response, primarily through the inhibition of NF-κB signaling.

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Aloin promotes A549 cell apoptosis via the reactive oxygen species-mitogen activated protein kinase signaling pathway and p53 phosphorylation

Cited by 38 publications

References 56 publications

<p>Aloin Inhibits the Proliferation and Migration of Gastric Cancer Cells by Regulating NOX2–ROS-Mediated Pro-Survival Signal Pathways</p>

<p>Aloin Inhibits the Proliferation and Migration of Gastric Cancer Cells by Regulating NOX2–ROS-Mediated Pro-Survival Signal Pathways</p>

Aloin suppresses lipopolysaccharide‑induced inflammation by inhibiting JAK1‑STAT1/3 activation and ROS production in RAW264.7 cells

Aloin Suppresses Lipopolysaccharide-Induced Inflammatory Response and Apoptosis by Inhibiting the Activation of NF-κB

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