Spermidine/spermine N1-acetyltransferase regulates cell growth and metastasis<i>via</i>AKT/β-catenin signaling pathways in hepatocellular and colorectal carcinoma cells

Wang, Cong; Ruan, Ping; Zhao, Ying; Li, Xiaomin; Wang, Jun; Wu, Xiaoxiao; Liu, Tong; Wang, Shasha; Hou, Jiuzhou; Li, Wei; Li, Qian; Li, Jinghua; Dai, Fujun; Fang, Dong; Wang, Chaojie; Xie, Songqiang

doi:10.18632/oncotarget.13582

Cited by 56 publications

(53 citation statements)

References 61 publications

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“…Polyamine depletion has been suggested for cancer prevention, but α-difluorometh ylornithine (DFMO) was not clinically effective neither alone nor in combination with other agents (28). Depletion of polyamines by spermidine/spermine N1-acetyltransferase (SSAT) significantly inhibited cellular proliferation, migration, and invasion through the AKT/GSK3β/β-catenin signaling pathway in hepatocellular carcinoma and colorectal cancer cells (29). However, previous studies reported that inhibition of spermidine production promoted colorectal cancer growth (15), and that exogenous spermidine suppressed hepatocellular carcinomas in mice (16).…”

Section: Discussionmentioning

confidence: 99%

Spermidine‑induced growth inhibition and apoptosis via autophagic activation in cervical cancer

et al. 2018

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Cervical cancer is the most common malignancy of the female reproductive tract, and the poor response to prophylactic vaccines and the toxicity of high‑dose chemotherapeutic drugs have limited their clinical application. Spermidine, a natural polyamine detected in all eukaryotic organisms, exhibits functions that promote longevity in multiple model systems and may constitute a promising agent for cancer treatment. However, the potential effectiveness of spermidine in cervical cancer has not yet been fully elucidated, and the underlying molecular mechanisms remain unclear. In the present study, we aimed to assess the effects of spermidine on proliferation and apoptosis of HeLa cells (a cervical cancer cell line). Firstly, CCK‑8 and flow cytometric assays revealed that spermidine reduced the proliferation of HeLa cells in a dose‑dependent fashion by arresting the cell cycle at the S phase. Secondly, flow cytometry incorporating Annexin V‑FITC/PI‑staining revealed that spermidine promoted the apoptosis of HeLa cells, and western blot analysis revealed that spermidine activated autophagy. Finally, spermidine‑activated autophagy mediated the inhibition of cell proliferation by spermidine and spermidine‑induced apoptosis in HeLa cells. Collectively, these results revealed a novel function for spermidine in inhibiting cellular proliferation and inducing apoptosis of HeLa cells by activating autophagy, which may have important implications for the use of spermidine in cervical cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Spermidine‑induced growth inhibition and apoptosis via autophagic activation in cervical cancer

et al. 2018

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“…Finally, the polyamines spermine (Spm) and spermidine (Spd) are often naturally present in food [8]. However, also their excess has been recently associated with potential health risks [9,10]. Despite their recognized toxicity, the limit concentrations of BAs in fermented foodstuffs are far from being adequately standardized by regulatory agencies.…”

Section: Introductionmentioning

confidence: 99%

Biogenic Amines in Traditional Fiore Sardo PDO Sheep Cheese: Assessment, Validation and Application of an RP-HPLC-DAD-UV Method

et al. 2019

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This contribution aimed to measure for the first time the amount of biogenic amines (BAs) in one of the most ancient and traditional sheep cheese produced in Sardinia, Italy: the Protected Designation of Origin (PDO) Fiore Sardo. To achieve this, an original RP-HPLC-DAD-UV method has been developed that was completely validated in terms of LoD, LoQ, linearity, precision and trueness, and tested on 36 real Fiore Sardo PDO cheese samples produced by four different cheesemakers and marketed by four stores. The average total concentration of the eight BAs (i.e., tyramine, tryptamine, histidine, putrescine, cadaverine, 2-phenylethylamine, spermine and spermidine) measured in Fiore Sardo cheese was 700 mg/kg, with a range between 170 mg/kg and 1,100 mg/kg. A great variability in the total amount of BAs has been evidenced among the Fiore Sardo marketed in the four stores as well as for the cheeses purchased in different times in the same store. Tyramine (350 mg/kg), putrescine (150 mg/kg), histamine (80 mg/kg) and cadaverine (30 mg/kg) are the most abundant BAs found in this matrix. Among the many factors concurring, the dominant microflora of Fiore Sardo PDO is likely the principal cause of the qualitative and quantitative distribution of BAs in this matrix. Finally, the total amount of BAs found in Fiore Sardo PDO is not able to cause any health alert situation for consumers.

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“…However, in our study, we found that DKK3 restoration decreases p-GSK3β and nuclear β-catenin expression in adult B-ALL. A recent study showed that spermidine/spermine N1-acetyltransferase (SSAT) overexpression inhibits β-catenin nuclear translocation and decreases p-GSK3β expression through AKT activation [ 37 ]. The Pseudomonas aeruginosa mannose-sensitive hemagglutinin (PA-MSHA) was reported to reduce β-catenin and p-GSK3β by affecting the PTEN/AKT signaling pathway [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Suppression of miR-708 inhibits the Wnt/β-catenin signaling pathway by activating DKK3 in adult B-all

Zhang

Cao

et al. 2017

Oncotarget

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Inactivation of Dickkopf-3 (DKK3) is closely associated with a poor prognosis in various solid tumor and hematologic malignancies. Promoter hypermethylation is one potential cause of DKK3 inactivation. However, whether other mechanisms lead to DKK3 inactivation and the subsequent effects of these inactivations on cell proliferation and the Wnt signaling pathway in adult B acute lymphoblastic leukemia (B-ALL) remain unclear. In the present study, we found that low DKK3 expression levels were associated with high miR-708 expression and promoter hypermethylation in adult B-ALL. miR-708 was confirmed to directly decrease DKK3 expression in Nalm-6 and BALL-1 cells. Additionally, a miR-708 inhibitor decreased cell proliferation mainly through apoptosis and cell cycle arrest at the G1 phase, and these effects were eliminated by DKK3 siRNA treatment. Moreover, the demethylating agent 5-aza-2′-deoxycytidine (5-aza) decreased the methylation state of the DKK3 promoter based on methylation-specific PCR (MSP) and bisulfite genomic sequencing PCR (BSP), although this demethylation effect was not enhanced by the miR-708 inhibitor. The miR-708 inhibitor or 5-aza significantly increased DKK3 expression and decreased p-GSK3β, cyclin D1 and nuclear and cytoplasmic β-catenin protein expression, indicating that the Wnt/β-catenin signaling pathway was inhibited. These effects became more pronounced when the miR-708 inhibitor and 5-aza were used simultaneously. These findings provide greater insights into the mechanisms that increase DKK3 expression and suggest that a miR-708 inhibitor and 5-aza might be useful as targeted therapies for adult B-ALL.

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Spermidine/spermine N1-acetyltransferase regulates cell growth and metastasisviaAKT/β-catenin signaling pathways in hepatocellular and colorectal carcinoma cells

Cited by 56 publications

References 61 publications

Spermidine‑induced growth inhibition and apoptosis via autophagic activation in cervical cancer

Spermidine‑induced growth inhibition and apoptosis via autophagic activation in cervical cancer

Biogenic Amines in Traditional Fiore Sardo PDO Sheep Cheese: Assessment, Validation and Application of an RP-HPLC-DAD-UV Method

Suppression of miR-708 inhibits the Wnt/β-catenin signaling pathway by activating DKK3 in adult B-all

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