Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, Tamilnadu 608022, India.
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, Tamilnadu 608022, India.
Biomed Pharmacother. 2017 Aug;92:661-671. doi: 10.1016/j.biopha.2017.05.128. Epub 2017 Jun 3.
Umbelliferone (UMB) has widespread pharmacological activity, comprising anti-inflammatory, anti-oxidant, anti-genotoxic and anti-immunomodulatory but the anticancer activity remains unknown in human oral carcinoma (HOC) KB cells. MTT assay determinations was revealed that treatment of KB cells with UMB, prevent and reduce the cell proliferation with the IC - 200μM as well as induces loss of cell viability, morphology change and internucleosomal DNA fragmentation in a concentration dependent manner. Acridine orange and ethidium bromide dual staining assay established that UMB induced apoptosis in KB cells in a dose dependent manner. Alkaline comet assay determination revealed UMB has the potential to increase oxidative DNA damage in KB cells through DNA tail formation significantly (p<0.05). Furthermore, UMB brought a dose-dependent elevation of reactive oxygen species (ROS), which is evidenced by the DCF fluorescence, altered the mitochondrial membrane potential in KB cells. Similarly, we observed increased DNA damage stimulated apoptotic morphological changes in UMB treated cells. Taken together, the present study suggests that UMB exhibits anticancer effect on KB cell line with the increased generation of intracellular ROS, triggered oxidative stress mediated depolarization of mitochondria, which contributes cell death via DNA damage as well as cell cycle arrest at G0/G1 phase. The results have also provided us insight in the pharmacological backgrounds for the potential use of UMB, to target divergent pathways of cell survival and cell death. To conclude UMB could develop as a novel candidate for cancer chemoprevention and therapy, which is our future focus and to develop a connectivity map between in vivo and in vitro activity.
响豆素（UMB）具有广泛的药理活性，包括抗炎、抗氧化、抗遗传毒性和免疫调节作用，但在人类口腔癌（HOC）KB 细胞中其抗癌活性尚不清楚。MTT 测定结果表明，UMB 处理 KB 细胞可预防和减少细胞增殖，IC 200μM 即可减少细胞活力，形态发生变化，并导致核小体间 DNA 片段化呈浓度依赖性。吖啶橙和溴化乙锭双重染色试验证实 UMB 以剂量依赖的方式诱导 KB 细胞凋亡。碱性彗星试验测定结果显示，UMB 可通过 DNA 尾巴形成显著增加 KB 细胞中的氧化 DNA 损伤（p<0.05）。此外，UMB 使 KB 细胞中的活性氧（ROS）产生剂量依赖性升高，这可以通过 DCF 荧光来证明，改变了 KB 细胞中线粒体膜电位。同样，我们观察到 UMB 处理的细胞中，细胞凋亡形态学变化伴随着 DNA 损伤的增加。综上所述，本研究表明 UMB 对 KB 细胞系表现出抗癌作用，其通过增加细胞内 ROS 的产生，引发氧化应激介导的线粒体去极化，导致细胞死亡，同时使细胞周期停滞在 G0/G1 期，从而导致细胞死亡。这些结果为 UMB 靶向细胞存活和细胞死亡的不同途径提供了药理学背景，为癌症化学预防和治疗提供了新的候选药物。这是我们未来的研究重点，并致力于建立体内和体外活性之间的连接图谱。
