Department of Biochemistry and Microbiology, Nelson Mandela University, Port Elizabeth, South Africa.
Department of Physiology, Nelson Mandela University, Port Elizabeth, South Africa.
Anticancer Res. 2020 Jan;40(1):229-238. doi: 10.21873/anticanres.13944.
BACKGROUND/AIM: We previously reported the potential of aminonaphthoquinone derivatives as therapeutic agents against breast and other oestrogen-responsive tumours when combined with curcumin. This study aimed at screening of novel aminonaphthoquinone derivatives (Rau 008, Rau 010, Rau 015 and Rau 018) combined with curcumin for cytotoxic, anti-angiogenic and anti-metastatic effects on MCF-7 and MDA-MB-231 breast cancer cells.
Cytotoxic and anti-angiogenic effects were analysed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and enzyme-linked immunosorbent assay; while anti-metastatic effects were measured using adhesion assay, Boyden chambers and Matrigel.
Curcumin combined with Rau 008 elicited marked cytotoxic effects in MCF-7 cells compared with the individual treatments, whereas when it was combined with Rau 015 and with Rau 018, it displayed similar effects in MDA-MB-231 cells. The anti-angiogenic effect of Rau 015 plus curcumin in MCF-7 cells and Rau 018 plus curcumin in MDA-MB-231 cells was more effective than individual treatments, while the metastatic capability of MDA-MB-231 cells was significantly reduced after treatment with the aminonaphthoquinone-curcumin combinations.
Aminonaphthoquinones may offer significant promise as therapeutic agents against breast cancer, particularly when combined with curcumin.
背景/目的:我们之前报道了氨基萘醌衍生物与姜黄素联合使用时作为治疗乳腺癌和其他雌激素反应性肿瘤的潜在药物。本研究旨在筛选新型氨基萘醌衍生物(Rau 008、Rau 010、Rau 015 和 Rau 018)与姜黄素联合使用对 MCF-7 和 MDA-MB-231 乳腺癌细胞的细胞毒性、抗血管生成和抗转移作用。
采用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐法和酶联免疫吸附试验分析细胞毒性和抗血管生成作用;采用黏附试验、Boyden 室和 Matrigel 测量抗转移作用。
与单独用药相比,姜黄素与 Rau 008 联合使用在 MCF-7 细胞中产生了明显的细胞毒性作用,而当与 Rau 015 和 Rau 018 联合使用时,在 MDA-MB-231 细胞中显示出相似的作用。Rau 015 加姜黄素在 MCF-7 细胞中的抗血管生成作用和 Rau 018 加姜黄素在 MDA-MB-231 细胞中的作用比单独用药更有效,而 MDA-MB-231 细胞的转移能力在接受氨基萘醌-姜黄素联合治疗后显著降低。
氨基萘醌类化合物可能具有很大的治疗乳腺癌的潜力,特别是与姜黄素联合使用时。