In Vivo Performance of a Ruthenium-cyclopentadienyl Compound in an Orthotopic Triple Negative Breast Cancer Model

• Published in: Anti-cancer agents in medicinal chemistry Vol. 17; no. 1; p. 126
• Main Authors: Mendes, Nuno, Tortosa, Francisco, Valente, Andreia, Marques, Fernanda, Matos, António, Morais, Tânia S, Tomaz, Ana Isabel, Gärtner, Fátima, Garcia, M Helena
• Format: Journal Article
• Language: English
• Published: Netherlands 2017
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - therapeutic use; Breast - drug effects; Breast - pathology; Cell Death - drug effects; Cell Line, Tumor; Female; Humans; Mice; Mice, Nude; Organometallic Compounds - chemistry; Organometallic Compounds - therapeutic use; Ruthenium - chemistry; Ruthenium - therapeutic use; Triple Negative Breast Neoplasms - drug therapy; Triple Negative Breast Neoplasms - pathology
• ISSN: 1875-5992
• DOI: 10.2174/1871520616666160922165133

Ruthenium-based anti-cancer compounds are proposed as viable alternatives that might circumvent the disadvantages of platinum-based drugs, the only metallodrugs in clinical use for chemotherapy. Organometallic complexes in particular hold great potential as alternative therapeutic agents since their cytotoxicity involves different modes of action and present reduced toxicity profiles. During the last few years our research group has been reporting on a series of organometallic ruthenium(II)- cyclopentadienyl complexes with important cytotoxicity against several cancer cell lines, surpassing cisplatin in activity. We report herein preliminary in vivo studies with one representative compound of this family, with exceptional activity against several human cancer cell lines, including the glycolytic and highly metastatic MDAMB231 cell line used in this study. The anti-tumor activity of our compound was studied in vivo on N:NIH(S)II-nu/nu nude female mice bearing triple negative breast cancer (TNBC) orthotopic tumors. Administration of 2.5 mg/kg/day during ten days caused cell death mostly by necrosis (in vitro and in vivo), inducing tumor growth suppression of about 50% in treated animals when compared to controls. The most remarkable result supporting the effectiveness and potential of this drug was the absence of metastases in the main organs of treated animals, while metastases were present in the lungs of all control mice, as revealed by histopathological and immunohistochemical analysis. These in vivo studies suggest a dual effect for our drug not only by suppressing growth at the primary tumor tissue but also by inhibiting its metastatic behavior. Altogether, these results represent a benchmark and a solid starting point for future studies.