Ou Jian, Meng Fanxu, Liu Jinyu, Li Dongqing, Cao Huifang, Sun Baosheng
Department of Radiotherapy and Jilin Cancer Hospital, Changchun, Jilin 130012, China.
J BUON. 2020 Jan-Feb;25(1):87-92.
Being the second most prevalent cancer in females, cervical cancer causes significant mortality across the globe. Owing to the adverse effects and inefficiency of the currently used anticancer drugs, there are increasing efforts for the identification of safer and effective anticancer agents from plants. This study was undertaken to investigate the anticancer effects of Ovatodiolide, a plant-derived macrocyclic diterpenoid, against the human cervical cancer.
The anticancer effects were examined by WST-1 proliferation assay. DAPI and annexin V/propidium iodide (PI) staining were used for apoptosis detection. Flow cytometry was used for cell cycle analysis. Protein expression was used for cell cycle analysis.
The results revealed that Ovatodiolide caused inhibition of the viability of all the cervical cancer cells with IC50 ranging from to 14 to 56 µM. Ovatodiolide exerted more profound antiproliferative effects on the DoTc2 cells with and IC50 of 14 µM. However, minimal cytotoxicity was observed for the normal cervical cells as evidenced from the IC50 of 100 µM. Ovatodiolide triggered apoptotic cell death of the DoTc2 cells. The induction of apoptosis was accompanied with increase in Bax and decrease in Bcl-2 expression. Ovatodiolide also caused arrest of the DoTc2 cells at the G2/M phase of the cell cycle, which was also accompanied with suppression of cyclin B1 expression. Investigation of the effects of Ovatodiolide on NF-kB expression revealed that the molecule caused significant decrease in the expression of the NF-kB expression.
Taken together, Ovatodiolide may prove a lead molecule for the development of systemic therapy for cervical cancer.
宫颈癌是女性中第二大常见癌症,在全球范围内导致大量死亡。由于目前使用的抗癌药物存在不良反应且效率低下,人们越来越致力于从植物中寻找更安全有效的抗癌药物。本研究旨在探讨植物来源的大环二萜奥伐二醇对人宫颈癌的抗癌作用。
通过WST-1增殖试验检测抗癌效果。采用DAPI和膜联蛋白V/碘化丙啶(PI)染色检测细胞凋亡。流式细胞术用于细胞周期分析。蛋白质表达用于细胞周期分析。
结果显示,奥伐二醇对所有宫颈癌细胞的活力均有抑制作用,IC50范围为14至56μM。奥伐二醇对DoTc2细胞具有更显著的抗增殖作用,IC50为14μM。然而,正常宫颈细胞的细胞毒性极小,IC50为100μM可证明这一点。奥伐二醇引发DoTc2细胞凋亡性死亡。凋亡的诱导伴随着Bax增加和Bcl-2表达减少。奥伐二醇还导致DoTc2细胞在细胞周期的G2/M期停滞,这也伴随着细胞周期蛋白B1表达的抑制。对奥伐二醇对NF-κB表达影响的研究表明,该分子导致NF-κB表达显著降低。
综上所述,奥伐二醇可能成为开发宫颈癌全身治疗药物的先导分子。