Department of Dental Hygiene, Chodang University, Muan‑ro, Muan‑eup, Muan 534‑701, Republic of Korea.
Department of Oral Biochemistry, College of Dentistry, Chosun University, Dong‑gu, Gwangju 501‑759, Republic of Korea.
Oncol Rep. 2018 Jun;39(6):2769-2776. doi: 10.3892/or.2018.6333. Epub 2018 Mar 27.
Anthricin (deoxypodophyllotoxin) is a major lignan in Anthriscus sylvestris and possesses many bioactivities such as antiproliferative, antitumor, anti‑platelet aggregation, antiviral and anti‑inflammatory actions. However, the anticancer effects of anthricin on A549 human non‑small cell lung cancer cells and potential molecular mechanisms remain unknown. Therefore, we investigated the anticancer effect of anthricin and the underlying mechanism in A549 cells. Anthricin (10‑200 nM) inhibited the viability of A549 cells in a dose‑ and time‑dependent manner. Moreover, anthricin‑induced apoptosis was confirmed by live and dead assay, 4,6‑dianmidino‑2‑phenylindole staining, and flow cytometric analysis. In addition, anthricin induced cell cycle arrest at the G2/M phase through suppression of the expression of cell cycle cascade proteins, Cdc2 and Cdc25C. Furthermore, it induced the expression of caspase‑related proteins and significantly suppressed the phosphorylation of insulin‑like growth factor 1 receptor (IGF1R), PI3K and Akt. Anthricin significantly inhibited tumor growth without any significant change in the body weight of mice in A549 tumor xenograft BALB/c nude mice. Anthricin induced caspase‑dependent apoptosis through the IGF1R/PI3K/Akt signaling pathway in A549 cells.
Anthricin（脱氧鬼臼毒素）是Anthriscus sylvestris 中的一种主要木质素，具有多种生物活性，如抗增殖、抗肿瘤、抗血小板聚集、抗病毒和抗炎作用。然而，Anthricin 对 A549 人非小细胞肺癌细胞的抗癌作用及其潜在的分子机制尚不清楚。因此，我们研究了 Anthricin 在 A549 细胞中的抗癌作用及其潜在机制。Anthricin（10-200 nM）以剂量和时间依赖性方式抑制 A549 细胞的活力。此外，通过死活检测、4,6-二脒基-2-苯基吲哚染色和流式细胞术分析证实了 Anthricin 诱导的细胞凋亡。此外，Anthricin 通过抑制细胞周期级联蛋白 Cdc2 和 Cdc25C 的表达，将细胞周期阻滞在 G2/M 期。此外，它诱导 Caspase 相关蛋白的表达，并显著抑制胰岛素样生长因子 1 受体 (IGF1R)、PI3K 和 Akt 的磷酸化。在 A549 肿瘤异种移植 BALB/c 裸鼠中，Anthricin 显著抑制肿瘤生长，而小鼠体重无明显变化。Anthricin 通过 IGF1R/PI3K/Akt 信号通路诱导 A549 细胞 Caspase 依赖性细胞凋亡。
