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


OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Nuno
N
Mendes
Francisco
F
Tortosa
Andreia
A
Valente
Fernanda
F
Marques
António
A
Matos
Tânia S
TS
Morais
Ana Isabel
AI
Tomaz
Fátima
F
Gärtner
Centro de Química Estrutural, Faculdade de Ciências da Universidade de Lisboa, Campo Grande, 1749- 016 Lisboa, Portugal.
M Helena
MH
Garcia
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D001940:Breast / Q000187:drug effects* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009942:Organometallic Compounds / Q000737:chemistry / Q000627:therapeutic use*; D012428:Ruthenium / Q000737:chemistry / Q000627:therapeutic use*; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology
D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D012428:Ruthenium