BACKGROUND/AIM: 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. MATERIALS AND METHODS: 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. RESULTS: Ti-Preg demonstrated significant inhibition of MCF-7 tumor growth when compared to vehicle and to titanocene controls. CONCLUSION: Our findings demonstrate the potential of steroid pendent groups for targeting chemotherapeutics to steroid hormone-dependent cancer.
BACKGROUND/AIM: 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. MATERIALS AND METHODS: 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. RESULTS:Ti-Preg demonstrated significant inhibition of MCF-7tumor growth when compared to vehicle and to titanocene controls. CONCLUSION: Our findings demonstrate the potential of steroid pendent groups for targeting chemotherapeutics to steroid hormone-dependent cancer.
Entities:
Keywords:
TLT-1; Titanocene; breast cancer; steroid pendant groups; titanocenyl-pregnenolone
Authors: James L Gattis; A Valance Washington; Maia M Chisholm; Laura Quigley; Agnieszka Szyk; Daniel W McVicar; Jacek Lubkowski Journal: J Biol Chem Date: 2006-02-27 Impact factor: 5.157
Authors: C V Christodoulou; D R Ferry; D W Fyfe; A Young; J Doran; T M Sheehan; A Eliopoulos; K Hale; J Baumgart; G Sass; D J Kerr Journal: J Clin Oncol Date: 1998-08 Impact factor: 44.544
Authors: José A Carmona-Negrón; Mariola M Flores-Rivera; Zaibeth Díaz-Reyes; Curtis E Moore; Arnold L Rheigold; Enrique Meléndez Journal: Acta Crystallogr E Crystallogr Commun Date: 2016-05-27