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New Insights into the Mechanisms of Polyphenol from Plum Fruit Inducing Apoptosis in Human Lung Cancer A549 Cells Via PI3K/AKT/FOXO1 Pathway
Plant Foods for Human Nutrition ( IF 3.1 ) Pub Date : 2021-02-27 , DOI: 10.1007/s11130-021-00882-y
Wenfeng Li , Mengting Cheng , Wentao Zhang , Ruiyan He , Hongyan Yang

Recent studies have been found that polyphenols from plums fruits can inhibit the proliferation of multiple cancer cells, while the molecular mechanism was unclear. This study aimed to investigate the molecular mechanism underlying the pro-apoptotic effect of purified plum polyphenols (PPP) on human lung cancer A549 cells. Quercitrin (quercetin-3-O-glucoside, 814.19 ± 40.71 mg/g) was identified as the primary polyphenol in PPP via ultra high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC-QqQ-MS/MS). PPP showed a strong capacity for inhibiting the proliferation of the A549 cells by inducing apoptosis, which was reflected by an increase in the Bax/Bcl-2 ratio. Additionally, the inhibitory rate of PPP on the A549 cells were higher than that of vitamin C when the treatment dose exceeded 160 μg/mL. Transcriptome analysis suggested that PPP-induced apoptosis was closely associated with regulating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/forkhead box protein O 1 (FOXO1) pathway in the A549 cells. Subsequently, as an activator of AKT, SC79 was applied to confirm that the inhibition of AKT phosphorylation play an important role in the PPP-induced apoptosis of the A549 cells. These results illustrated the potential of PPP as a dietary compound for the prevention of cancer or for use during chemotherapy.



中文翻译:

李子多酚通过PI3K / AKT / FOXO1途径诱导人肺癌A549细胞凋亡机制的新见解

最近的研究发现,李子果实中的多酚可以抑制多种癌细胞的增殖,但其分子机制尚不清楚。这项研究旨在调查纯化的李子多酚(PPP)对人肺癌A549细胞促凋亡作用的分子机制。槲皮素(槲皮素3- O通过超高效液相色谱与三重四极杆质谱联用(UHPLC-QqQ-MS / MS),将814.19±40.71 mg / gβ-葡糖苷鉴定为PPP中的主要多酚。PPP通过诱导凋亡显示出强大的抑制A549细胞增殖的能力,这可以通过Bax / Bcl-2比值的增加来体现。另外,PPP对A549细胞的抑制率较维生素C较高,当治疗剂量超过160  μ克/毫升。转录组分析表明,PPP诱导的凋亡与调节A549细胞中的磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(AKT)/叉头盒蛋白O 1(FOXO1)途径密切相关。随后,使用SC79作为AKT的激活剂,以证实AKT磷酸化的抑制作用在PPP诱导的A549细胞凋亡中起着重要作用。这些结果说明了PPP作为饮食化合物预防癌症或在化学疗法中使用的潜力。

更新日期:2021-02-28
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