Department of Health Sciences, University Magna Græcia of Catanzaro, Viale Europa, Germaneto, Campus S. Venuta, 88100 Catanzaro, Italy.
J Mol Endocrinol. 2013 Jun 29;51(1):181-9. doi: 10.1530/JME-12-0241. Print 2013.
The olive tree phenolic component oleuropein (OLE) and its derivatives have shown many biological properties, thus representing promising novel therapeutics for the treatment of several diseases, including neoplasia. In this study, we evaluated the activities of OLE and its peracetylated derivative (peracetylated oleuropein, Ac-OLE) against two thyroid tumor cell lines that host genotypic alterations detected in human papillary thyroid cancer. TPC-1 and BCPAP cells were treated with OLE and Ac-OLE, and the effects on viability were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, cell counting, and trypan blue exclusion assays. Antioxidant effects were analyzed by measuring the reactive oxygen species (ROS) in basal conditions and after treatment with hydrogen peroxide (H2O2). Activity of MAP kinase and PI3K-Akt signaling pathways was evaluated by examining the levels of phosphorylated ERK and Akt by western blot. We found that OLE significantly inhibited the proliferation of both cell lines. This effect was paralleled by a reduction of basal phospho-Akt and phospho-ERK levels and H2O2-induced ROS levels. A stronger effect was elicited by Ac-OLE either in inhibiting cell growth or as an antioxidant, in particular on BCPAP cells. Our results demonstrate that OLE and especially Ac-OLE inhibit in vitro thyroid cancer cell proliferation acting on growth-promoting signal pathways, as well as exerting antioxidant effects. Further studies will reveal the potential application as novel targeted therapeutics in thyroid cancer.
橄榄树酚类成分橄榄苦苷(OLE)及其衍生物具有多种生物学特性,因此代表了治疗多种疾病(包括肿瘤)的有前途的新型治疗方法。在这项研究中,我们评估了 OLE 及其乙酰化衍生物(乙酰化橄榄苦苷,Ac-OLE)对两种甲状腺肿瘤细胞系的活性,这两种细胞系中存在人甲状腺乳头状癌中检测到的基因改变。用 OLE 和 Ac-OLE 处理 TPC-1 和 BCPAP 细胞,通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐、细胞计数和台盼蓝排除试验评估对活力的影响。通过测量基础条件下和用过氧化氢(H2O2)处理后的活性氧物种(ROS)来分析抗氧化作用。通过 Western blot 检查磷酸化 ERK 和 Akt 的水平来评估 MAP 激酶和 PI3K-Akt 信号通路的活性。我们发现 OLE 显著抑制了两种细胞系的增殖。这种作用伴随着基础磷酸化 Akt 和磷酸化 ERK 水平以及 H2O2 诱导的 ROS 水平的降低。Ac-OLE 无论是在抑制细胞生长还是作为抗氧化剂方面,对 BCPAP 细胞的作用更强。我们的结果表明,OLE 尤其是 Ac-OLE 通过作用于促生长信号通路来抑制体外甲状腺癌细胞增殖,并发挥抗氧化作用。进一步的研究将揭示其在甲状腺癌中作为新型靶向治疗的潜在应用。