Ozkan Erva, Bakar-Ates Filiz
Department of Biochemistry, Faculty of Pharmacy, Ankara University, Dogol Street, 06560, Ankara, Turkey.
An Acad Bras Cienc. 2020 Nov 20;92(4):e20200548. doi: 10.1590/0001-3765202020200548. eCollection 2020.
Combination therapies are becoming increasingly important to develop an effective treatment in cancer. Lonidamine is frequently used in cancer treatment, but it's often preferred to be used in combination with other drugs because of its side effects. In the present study, the efficacy of the combination of lonidamine with quercetin, a flavonoid of natural origin, on human MCF-7 breast cancer cells was evaluated. The results showed that the combined use of the compounds significantly increased cytotoxicity compared to administration alone (p<0.0001). In addition, while lonidamine induced a cell cycle arrest in the G2/M phase, administration of quercetin and its combination with lonidamine arrested the cell division at S point, indicating the synergistic strength of quercetin on cytotoxicity. The combination of quercetin and lonidamine significantly induced apoptosis of MCF-7 cells (p<0.0001) and increased caspase levels (p<0.0001). In this study, the combination of quercetin and lonidamine has been evaluated for the first time and the combination treatment decreased MMP-2/-9 mRNA expression more potently than the effects of the compounds alone. The results showed that lonidamine was more effective when combined with quercetin, and their combination may be a candidate for a novel strategy of treatment for breast cancer.
联合疗法对于开发有效的癌症治疗方法正变得越来越重要。氯尼达明常用于癌症治疗，但由于其副作用，通常更倾向于与其他药物联合使用。在本研究中，评估了氯尼达明与天然来源的类黄酮槲皮素联合使用对人MCF - 7乳腺癌细胞的疗效。结果表明，与单独给药相比，联合使用这些化合物显著增加了细胞毒性（p<0.0001）。此外，虽然氯尼达明诱导细胞周期停滞在G2/M期，但槲皮素及其与氯尼达明的联合给药使细胞分裂停滞在S期，表明槲皮素在细胞毒性方面的协同作用强度。槲皮素和氯尼达明的联合使用显著诱导了MCF - 7细胞的凋亡（p<0.0001）并增加了半胱天冬酶水平（p<0.0001）。在本研究中，首次评估了槲皮素和氯尼达明的联合使用，并且联合治疗比单独使用化合物更有效地降低了MMP - 2/-9 mRNA的表达。结果表明，氯尼达明与槲皮素联合使用时更有效，它们的联合可能是乳腺癌治疗新策略的一个候选方案。
