Institute of Biochemistry and Molecular Biology, Guangdong Medical University, Zhanjiang, Guangdong 524023, P.R. China.
Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, Zhanjiang, Guangdong 524023, P.R. China.
Oncol Rep. 2018 Jun;39(6):2899-2905. doi: 10.3892/or.2018.6347. Epub 2018 Mar 30.
Cytochalasin H (CyH) has been shown to exhibit promising anticancer activities against various types of cancers; however, the underlying mechanisms remain unknown. In a previous study, we isolated CyH from the mangrove‑derived endophytic fungus Phomopsis sp. in Zhanjiang, China. In the present study, we further explored the effect of CyH on apoptosis and migration in the human lung adenocarcinoma cell line A549. Cell Counting kit‑8 (CCK‑8) assay was used to observe the effects of CyH on the growth of A549 cells. The cell cycle and apoptosis were determined using flow cytometry. The effect of CyH on cell migration was observed by scratch wound healing and chamber migration assays. Western blotting was used to detect the expression of apoptosis‑ and metastasis‑associated proteins. Our results showed that CyH exhibited cytotoxicity to A549 cells. The treatment of CyH arrested A549 cells at the G2/M phase. Furthermore, sub‑G1 peaks and fragmented DNA ladders were observed, and the mitochondrial transmembrane potential was also decreased in CyH‑treated A549 cells. CyH significantly increased Bax, P53, and cleaved caspase‑3 (17 kDa) protein expression and decreased Bcl‑xL, Bcl‑2, and full‑length caspase‑3 (35 kDa) protein expression, resulting in an increased ratio of the pro‑apoptosis/anti‑apoptosis proteins Bax/Bcl‑2. Additionally, CyH treatment inhibited the migration ability of A549 cells in a dose‑dependent manner. Taken together, our results suggest that CyH may be a potential chemopreventive drug for the treatment of lung cancer.
细胞松弛素 H（CyH）已被证明对多种类型的癌症具有有前途的抗癌活性；然而，其潜在机制尚不清楚。在之前的研究中，我们从中国湛江红树林内生真菌 Phomopsis sp. 中分离出 CyH。在本研究中，我们进一步探讨了 CyH 对人肺腺癌细胞系 A549 凋亡和迁移的影响。细胞计数试剂盒-8（CCK-8） assay 用于观察 CyH 对 A549 细胞生长的影响。通过流式细胞术测定细胞周期和细胞凋亡。划痕愈合和室迁移测定观察 CyH 对细胞迁移的影响。Western blot 用于检测凋亡和转移相关蛋白的表达。我们的结果表明，CyH 对 A549 细胞表现出细胞毒性。CyH 处理使 A549 细胞停滞在 G2/M 期。此外，在 CyH 处理的 A549 细胞中观察到 sub-G1 峰和 DNA 梯状片段，线粒体跨膜电位也降低。CyH 显著增加 Bax、P53 和 cleaved caspase-3（17 kDa）蛋白表达，降低 Bcl-xL、Bcl-2 和全长 caspase-3（35 kDa）蛋白表达，导致促凋亡/抗凋亡蛋白 Bax/Bcl-2 的比值增加。此外，CyH 处理以剂量依赖性方式抑制 A549 细胞的迁移能力。综上所述，我们的结果表明 CyH 可能是治疗肺癌的潜在化疗药物。
