Ghasemali Samaneh, Nejati-Koshki Kazem, Tafsiri Elham, Rahmati-Yamchi Mohamad, Akbarzadeh Abolfazl, Alizadeh Effat, Abbasi Mozhgan, Barkhordari Amin, Tozihi Majid, Kordi Shirafkan, Zarghami Nosratollah
Drug Applied Research Center, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran E-mail :
Asian Pac J Cancer Prev. 2013;14(11):6949-53. doi: 10.7314/apjcp.2013.14.11.6949.
Nowadays, the encapsulation of cytotoxic chemotherapeutic agents is attracting interest as a method for drug delivery. We hypothesized that the efficiency of helenalin might be maximized by encapsulation in β-cyclodextrin nanoparticles. Helenalin, with a hydrophobic structure obtained from flowers of Arnica chamissonis and Arnica Montana, has anti-cancer and anti-inflammatory activity but low water solubility and bioavailability. β-Cyclodextrin (β-CD) is a cyclic oligosaccharide comprising seven D-glucopyranoside units, linked through 1,4-glycosidic bonds.
To test our hypothesis, we prepared β-cyclodextrin- helenalin complexes to determine their inhibitory effects on telomerase gene expression by real-time polymerase chain reaction (q-PCR) and cytotoxic effects by colorimetric cell viability (MTT) assay.
MTT assay showed that not only β-cyclodextrin has no cytotoxic effect on its own but also it demonstrated that β-cyclodextrin- helenalin complexes inhibited the growth of the T47D breast cancer cell line in a time and dose-dependent manner. Our q-PCR results showed that the expression of telomerase gene was effectively reduced as the concentration of β-cyclodextrin-helenalin complexes increased.
β-Cyclodextrin-helenalin complexes exerted cytotoxic effects on T47D cells through down-regulation of telomerase expression and by enhancing Helenalin uptake by cells. Therefore, β-cyclodextrin could be superior carrier for this kind of hydrophobic agent.
如今，作为一种药物递送方法，细胞毒性化疗药物的包封正引起人们的关注。我们推测，通过将海伦alin包封在β-环糊精纳米颗粒中，其效率可能会最大化。海伦alin具有从山金车花和山金车中获得的疏水结构，具有抗癌和抗炎活性，但水溶性和生物利用度较低。β-环糊精（β-CD）是一种环状寡糖，由七个D-吡喃葡萄糖苷单元组成，通过1,4-糖苷键连接。
为了验证我们的假设，我们制备了β-环糊精-海伦alin复合物，通过实时聚合酶链反应（q-PCR）测定其对端粒酶基因表达的抑制作用，并通过比色细胞活力（MTT）测定法测定其细胞毒性作用。
MTT测定表明，β-环糊精本身不仅没有细胞毒性作用，而且还表明β-环糊精-海伦alin复合物以时间和剂量依赖性方式抑制T47D乳腺癌细胞系的生长。我们的q-PCR结果表明，随着β-环糊精-海伦alin复合物浓度的增加，端粒酶基因的表达有效降低。
β-环糊精-海伦alin复合物通过下调端粒酶表达并增强细胞对海伦alin的摄取，对T47D细胞发挥细胞毒性作用。因此，β-环糊精可能是这类疏水剂的优良载体。
