Centre of Natural Products & Drug Discovery (CENAR), Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Molecules. 2011 Mar 21;16(3):2583-98. doi: 10.3390/molecules16032583.
In the present study we investigated the effects of panduratin A, isolated from Boesenbergia rotunda, on proliferation and apoptosis in A549 human non-small cell lung cancer cells. Cell proliferation and induction of apoptosis was determined by the real-time cellular analyzer (RTCA), MTT assay and High Content Screening (HCS). The RTCA assay indicated that panduratin A exhibited cytotoxicity, with an IC₅₀ value of 4.4 µg/mL (10.8 µM). Panduratin A arrested cancer cells labeled with bromodeoxyuridine (BrdU) and phospho-Histone H3 in the mitotic phase. The cytotoxic effects of panduratin A were found to be accompanied by a dose-dependent induction of apoptosis, as assessed by DNA condensation, nuclear morphology and intensity, cell permeability, mitochondrial mass/ potential, F-actin and cytochrome c. In addition, treatment with an apoptosis-inducing concentration of panduratin A resulted in significant inhibition of Nuclear Factor-kappa Beta (NF-κB) translocation from cytoplasm to nuclei activated by tumor necrosis factor-alpha (TNF-α), as illustrated by the HCS assay. Our study provides evidence for cell growth inhibition and induction of apoptosis by panduratin A in the A549 cell line, suggesting its therapeutic potential as an NF-κB inhibitor.
在本研究中,我们研究了从蓬莪术分离得到的波当亭 A 对 A549 人非小细胞肺癌细胞增殖和凋亡的影响。通过实时细胞分析(RTCA)、MTT 测定和高内涵筛选(HCS)测定细胞增殖和诱导凋亡。RTCA 测定表明,波当亭 A 表现出细胞毒性,IC₅₀值为 4.4 µg/mL(10.8 µM)。波当亭 A 将标记有溴脱氧尿苷(BrdU)和磷酸化组蛋白 H3 的癌细胞阻滞在有丝分裂期。细胞毒性作用伴随着细胞凋亡的剂量依赖性诱导,如 DNA 浓缩、核形态和强度、细胞通透性、线粒体质量/电位、F-肌动蛋白和细胞色素 c 的变化所证明的那样。此外,用诱导凋亡浓度的波当亭 A 处理导致肿瘤坏死因子-α(TNF-α)激活的核因子-κB(NF-κB)从细胞质向细胞核易位的显著抑制,如 HCS 测定所示。我们的研究为波当亭 A 在 A549 细胞系中抑制细胞生长和诱导细胞凋亡提供了证据,表明其作为 NF-κB 抑制剂的治疗潜力。