In Vitro Analysis of the Combinatory Effects of Novel Aminonaphthoquinone Derivatives and Curcumin on Breast Cancer Progression

• Published in: Anticancer research 2020-01, Vol.40 (1), p.229-238
• Main Authors: Pereira, Melanie C, Mohammed, Raushaan, VAN Otterlo, Willem A L, DE Koning, Charles B, Davids, Hajierah
• Format: Article
• Language: English
• Subjects: Adhesion tests; Angiogenesis; Antiangiogenics; Assaying; Breast cancer; Breast Neoplasms - blood supply; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cell Adhesion - drug effects; Cell Movement - drug effects; Cell Survival - drug effects; Chemical compounds; Curcumin; Curcumin - chemistry; Curcumin - pharmacology; Curcumin - therapeutic use; Cytotoxicity; Derivatives; Disease Progression; Enzyme-linked immunosorbent assay; Estrogens; Extracellular Matrix - metabolism; Female; Humans; MCF-7 Cells; Metastases; Metastasis; Naphthoquinones - chemistry; Naphthoquinones - pharmacology; Neoplasm Invasiveness; Neovascularization, Pathologic - drug therapy; Pharmacology; Tumors; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 0250-7005; 1791-7530
• DOI: 10.21873/anticanres.13944

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.