The Basic Medical College, Hebei Medical University, Shijiazhuang, 050017, PR China.
The Basic Medical College, Hebei Medical University, Shijiazhuang, 050017, PR China.
Eur J Pharmacol. 2021 Sep 15;907:174299. doi: 10.1016/j.ejphar.2021.174299. Epub 2021 Jul 1.
Extensive investigations have revealed that iso-suillin, a secondary metabolite isolated from Suillus flavus, could induce cell cycle arrest and apoptosis in human chronic myeloid leukemia K562 cells, human hepatocellular carcinoma SMMC-7721 cell line, and human small cell lung cancer H446 cell line in vitro. In the present study, human lung cancer A549 cells were used to reveal the mechanism of iso-suillin's effects on lung adenocarcinoma, which were detected both in vitro and in vivo. Results showed that iso-suillin potently inhibited A549 cell proliferation through an early G arrest. Iso-suillin also induced A549 cell apoptosis in vitro. Phosphorylation of p53 at serines 15 and 20 may be one of the pivotal factors for cell cycle arrest and apoptosis after treatment of iso-suillin in A549 cells. Moreover, in an A549 xenograft model, tumor growth and progression could be inhibited by iso-suillin. Body weight change and some vital organs toxicity was also roughly examined, no significant toxic effects of iso-suillin were shown (at a dose of 5 mg/kg for each administration). The in vitro and in vivo anti-tumor effects implied that iso-suillin may act as a tumor growth inhibitor, and its induction of p53 phosphorylation is pivotal for cell cycle arrest and apoptosis in A549 cells.
大量研究表明，从美味牛肝菌中分离得到的次生代谢产物异齿菌醇能在体外诱导人慢性髓性白血病 K562 细胞、人肝癌 SMMC-7721 细胞系和人小细胞肺癌 H446 细胞系的细胞周期停滞和凋亡。本研究采用人肺癌 A549 细胞，进一步探讨异齿菌醇对肺腺癌的作用机制，包括体内和体外实验。结果表明，异齿菌醇能通过早期 G1 期阻滞强力抑制 A549 细胞增殖。异齿菌醇还能诱导 A549 细胞凋亡。异齿菌醇处理 A549 细胞后，p53 丝氨酸 15 和 20 的磷酸化可能是细胞周期阻滞和凋亡的关键因素之一。此外，在 A549 异种移植模型中，异齿菌醇能抑制肿瘤生长和进展。我们还粗略检查了体重变化和一些重要器官的毒性，未显示异齿菌醇有明显的毒性作用（每次给药剂量为 5mg/kg）。体外和体内的抗肿瘤作用表明，异齿菌醇可能作为一种肿瘤生长抑制剂，其诱导 p53 磷酸化对 A549 细胞的细胞周期阻滞和凋亡至关重要。
