The addition of a pregnenolone pendant group enhances the anticancer properties of titanocene dichloride in a mcf-7 xenograft model

Titanocene dichloride held great promise as a chemotherapeutic compound in pre-clinical studies. However, subsequent clinical trials revealed hepatoxicity and nephrotoxicity, which limited its use in clinical applications. Therefore, we used steroid pendant groups to improve the targeting of titanoc...

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Bibliographic Details
Published in:Anticancer research 2014-04, Vol.34 (4), p.1609-1616
Main Authors: Ramos, Gladiany, Loperena, Yaliz, Ortiz, Giovanni, Reyes, Fiorella, Szeto, Ada, Vera, Jose, Velez, Javier, Morales, Jessica, Morrero, Deborah, Castillo, Linnette, Dharmawardhane, Surangani, Melendez, Enrique, Washington, A Valance
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Cell Line, Tumor
Cell Proliferation - drug effects
Drug Synergism
Female
Humans
Kidney - drug effects
Kidney - pathology
Liver - drug effects
Liver - pathology
MCF-7 Cells
Mice
Organometallic Compounds - administration & dosage
Organometallic Compounds - chemistry
Organometallic Compounds - pharmacology
Pregnenolone - administration & dosage
Pregnenolone - chemistry
Pregnenolone - pharmacology
Tumor Burden - drug effects
Xenograft Model Antitumor Assays
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Summary:Titanocene dichloride held great promise as a chemotherapeutic compound in pre-clinical studies. However, subsequent clinical trials revealed hepatoxicity and nephrotoxicity, which limited its use in clinical applications. Therefore, we used steroid pendant groups to improve the targeting of titanocene in MCF-7 breast cancer cells, and demonstrated a 10-fold lower effective dose compared to titanocene in in vitro assays. The aim of the present study was to test the efficacy of a titanocene functionalized with pregnenolone (Ti-Preg) in an in vivo breast cancer model. Xenografts from the MCF7 breast cancer cell line were implanted into athymic nu/nu mice to evaluate the potential of Ti-Preg as an anti-breast cancer agent. Ti-Preg demonstrated significant inhibition of MCF-7 tumor growth when compared to vehicle and to titanocene controls. Our findings demonstrate the potential of steroid pendent groups for targeting chemotherapeutics to steroid hormone-dependent cancer.
ISSN:0250-7005
1791-7530