Dey Tapan, Dutta Prachurjya, Manna Prasenjit, Kalita Jatin, Boruah Hari Prasanna Deka, Buragohain Alak Kumar, Unni Balagopalan
Biological Sciences and Technology Division, CSIR-North East Institute of Science and Technology, Jorhat 785006, India.
Centre for Biotechnology and Bioinformatics, Dibrugarh University, Dibrugarh 786004, India.
Biomol Ther (Seoul). 2018 Jul 1;26(4):409-416. doi: 10.4062/biomolther.2017.097.
Vasicinone, a quinazoline alkaloid from Nees. is well known for its bronchodilator activity. However its anti-proliferative activities is yet to be elucidated. Here-in we investigated the anti-proliferative effect of vasicinone and its underlying mechanism against A549 lung carcinoma cells. The A549 cells upon treatment with various doses of vasicinone (10, 30, 50, 70 μM) for 72 h showed significant decrease in cell viability. Vasicinone treatment also showed DNA fragmentation, LDH leakage, and disruption of mitochondrial potential, and lower wound healing ability in A549 cells. The Annexin V/PI staining showed disrupted plasma membrane integrity and permeability of PI in treated cells. Moreover vasicinone treatment also lead to down regulation of Bcl-2, Fas death receptor and up regulation of PARP, BAD and cytochrome c, suggesting the anti-proliferative nature of vasicinone which mediated apoptosis through both Fas death receptors as well as Bcl-2 regulated signaling. Furthermore, our preliminary studies with vasicinone treatment also showed to lower the ROS levels in A549 cells and have potential free radical scavenging (DPPH, Hydroxyl) activity and ferric reducing power in cell free systems. Thus combining all, vasicinone may be used to develop a new therapeutic agent against oxidative stress induced lung cancer.
鸭嘴花酮碱是一种从腺叶鸭嘴花中提取的喹唑啉生物碱，以其支气管扩张活性而闻名。然而，其抗增殖活性尚未阐明。在此，我们研究了鸭嘴花酮碱对A549肺癌细胞的抗增殖作用及其潜在机制。用不同剂量（10、30、50、70 μM）的鸭嘴花酮碱处理A549细胞72小时后，细胞活力显著下降。鸭嘴花酮碱处理还导致A549细胞出现DNA片段化、乳酸脱氢酶泄漏、线粒体膜电位破坏以及伤口愈合能力降低。膜联蛋白V/碘化丙啶染色显示处理后的细胞中质膜完整性受损且碘化丙啶通透性增加。此外，鸭嘴花酮碱处理还导致Bcl-2、Fas死亡受体下调，PARP、BAD和细胞色素c上调，这表明鸭嘴花酮碱具有抗增殖特性，它通过Fas死亡受体以及Bcl-2调节的信号传导介导细胞凋亡。此外，我们对鸭嘴花酮碱处理的初步研究还表明，它能降低A549细胞中的活性氧水平，并且在无细胞体系中具有潜在的自由基清除（二苯基苦味酰基自由基、羟基自由基）活性和铁还原能力。综上所述，鸭嘴花酮碱可用于开发一种针对氧化应激诱导的肺癌的新型治疗药物。
