Tian Qi, Wang Luying, Sun Xin, Zeng Fei, Pan Qiong, Xue Min
Department of Obstetrics and Gynecology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, 410013, China.
J BUON. 2019 May-Jun;24(3):997-1002.
Cervical cancer causes considerable mortality in women world over and the current treatment options create severe adverse effects. Hence, there is an urgent need to develop novel and efficient treatment regimens for cervical cancer. Herein, we examined the anticancer effects of a natural coumarin, Scopoletin, against a panel of cervical cancer cell lines.
The antiproliferative effect of Scopoletin was examined by cell counting and colony formation assays. Apoptosis was detected by acridine orange (AO) ethidium promide (EB) staining. Cell cycle distribution was determined by flow cytometry. Cell invasion was examined by Boyden chamber assay. Protein expression was checked by western blotting.
Scopoletin inhibited the growth of all the cell lines and the IC50 ranged between 7.5 to 25 µM. Nonetheless, the cytotoxic effects of Scopoletin were comparatively negligible against the normal cells with an IC50 of 90 µM. Investigation of the mechanism of action, revealed that the anticancer effects of Scopoletin against the HeLa cervical cancer cells were due to induction of apoptotic cell death as indicated AO/EB staining. Scopoletin treatment also resulted in enhancement of the Bax, Caspase 3, 8 and 9 expression and decline of the Bcl-2 expression. Scopoletin also blocked the HeLa cells at G2/M checkpoint of the cell cycle. Furthermore, cell invasion assay revealed that Scopoletin inhibited the migration of the HeLa cells concentration-dependently. PI3K/AKT is an imperative pathway involved in theproliferation and tumorigenesis of cancer cells and herein it was found that Scopoletin could inhibit this pathway.
Taken together, Scopoletin may prove essential in the development of novel treatment regimes for cervical cancer.
宫颈癌在全球女性中导致相当高的死亡率，而目前的治疗方案会产生严重的不良反应。因此，迫切需要开发针对宫颈癌的新型高效治疗方案。在此，我们研究了一种天然香豆素——东莨菪素对一组宫颈癌细胞系的抗癌作用。
通过细胞计数和集落形成试验检测东莨菪素的抗增殖作用。用吖啶橙（AO）-溴化乙锭（EB）染色检测细胞凋亡。通过流式细胞术测定细胞周期分布。用Boyden小室试验检测细胞侵袭。通过蛋白质印迹法检测蛋白质表达。
东莨菪素抑制了所有细胞系的生长，IC50在7.5至25μM之间。然而，东莨菪素对正常细胞的细胞毒性作用相对较小，IC50为90μM。对作用机制的研究表明，东莨菪素对人宫颈癌HeLa细胞的抗癌作用是由于诱导凋亡性细胞死亡，如AO/EB染色所示。东莨菪素处理还导致Bax、半胱天冬酶3、8和9表达增强以及Bcl-2表达下降。东莨菪素还使HeLa细胞在细胞周期的G2/M期检查点停滞。此外，细胞侵袭试验表明，东莨菪素浓度依赖性地抑制HeLa细胞的迁移。PI3K/AKT是参与癌细胞增殖和肿瘤发生的重要信号通路，在此发现东莨菪素可以抑制该信号通路。
综上所述，东莨菪素可能在开发宫颈癌新型治疗方案中至关重要。
