Pectolinarigenin (PEC), a natural flavonoid present in Cirsium chanroenicum and in some species of Citrus fruits, has various pharmacological benefits such as anti-inflammatory and anti-cancer activities. In the present study, we investigated the anti-cancer mechanism of PEC induced cell death caused by autophagy and apoptosis in AGS and MKN28 human gastric cancer cells. The PEC treatment significantly inhibited the AGS and MKN28 cell growth in a dose-dependent manner. Further, PEC significantly elevated sub-G1 phase in AGS cells and G2/M phase cell cycle arrest in both AGS and MKN28 cells. Apoptosis was confirmed by Annexin V and Hoechst 33342 fluorescent staining. Moreover, Immunoblotting results revealed that PEC treatment down-regulated the inhibitor of apoptosis protein (IAP) family protein XIAP that leads to the activation of caspase-3 thereby cleavage of PARP (poly-ADP-ribose polymerase) in both AGS and MKN28 cells in a dose-dependent manner. The autophagy-inducing effect was indicated by the increased formation of acidic vesicular organelles (AVOs) and increased protein levels of LC3-II conversion in both AGS and MKN28 cells. PEC shows the down regulation of PI3K/AKT/mTOR pathway which is a major regulator of autophagic and apoptotic cell death in cancer cells that leads to the down-regulation of p-4EBP1, p-p70S6K, and p-eIF4E in PEC treated cells when compared with the untreated cells. In conclusion, PEC treatment might have anti-cancer effect by down-regulation of PI3K/AKT/mTOR pathway leading to G2/M phase cell cycle arrest, autophagic and apoptotic cell death in human gastric cancer cells. Further studies of PEC treatment can support to develop as a potential alternative therapeutic agent for human gastric carcinoma.

中文翻译：

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Pectolinarigenin通过PI3K / AKT / mTOR信号通路诱导胃癌细胞的细胞周期阻滞，自噬和凋亡。

果胶苷（PEC）是存在于黄皮枸杞和某些柑橘类水果中的天然类黄酮，具有多种药理作用，例如抗炎和抗癌活性。在本研究中，我们研究了PEC诱导的AGS和MKN28人胃癌细胞自噬和凋亡引起的细胞死亡的抗癌机制。PEC处理以剂量依赖的方式显着抑制AGS和MKN28细胞的生长。此外，PEC显着提高了AGS细胞中的sub-G1期和AGS和MKN28细胞中的G2 / M期细胞周期阻滞。膜联蛋白V和Hoechst 33342荧光染色证实了细胞凋亡。而且，免疫印迹结果表明，PEC处理下调了凋亡蛋白（IAP）家族蛋白XIAP的抑制剂，该抑制剂导致caspase-3活化，从而在一定剂量下在AGS和MKN28细胞中裂解PARP（poly-ADP-核糖聚合酶）依赖的方式。在AGS和MKN28细胞中，酸性水泡细胞器（AVOs）的形成增加和LC3-II转换的蛋白质水平增加，表明了自噬诱导作用。PEC显示出PI3K / AKT / mTOR通路的下调，它是癌细胞自噬和凋亡细胞死亡的主要调节剂，导致PEC处理细胞中p-4EBP1，p-p70S6K和p-eIF4E的下调。与未经处理的细胞相比 综上所述，PEC治疗可能通过下调PI3K / AKT / mTOR途径而导致抗癌作用，导致人胃癌细胞中G2 / M期细胞周期停滞，自噬和凋亡细胞死亡。对PEC治疗的进一步研究可以支持其发展为潜在的人胃癌替代治疗剂。