Iron withdrawal strategies fail to prevent the growth of SiHa-induced tumors in mice.
OBJECTIVE
Cervical carcinoma is a human papillomavirus (HPV)-associated cancer for which treatment options still mainly rely on surgical procedures, with or without adjuvant radiotherapy and chemotherapy. We have previously shown that the chemically unrelated iron chelators desferrioxamine and deferiprone inhibit the growth and induce the apoptosis of HPV-positive cervical carcinoma cell lines, suggesting that iron chelators may represent a potential therapeutic approach for the treatment of cervical carcinoma. The present study was designed to investigate the effect of iron deprivation on the growth of human cervical carcinoma xenografts in athymic nude mice.


METHODS
Nude mice (nu/nu) of BALB/c background were treated with iron chelators [desferrioxamine (DFO), deferiprone (L1), or starch-DFO conjugate] or were fed with an iron-poor diet 6 weeks prior to subcutaneous injection of Si-Ha cells. These treatments were continued for 5 weeks after injection of the tumor cells. Treatment with the maximum tolerated doses of DFO, L1, or starch-DFO conjugate induced no significant iron deprivation in non-iron-overloaded mice, while an iron-poor diet led to a dramatic decrease in serum iron, transferrin iron saturation, and ferritin levels. However, neither iron chelators nor an iron-poor diet could significantly inhibit tumor growth.


CONCLUSIONS
Despite a potent antitumor effect in vitro, iron chelators fail to prevent the growth of cervical carcinoma xenografts in mice. On the basis of these results, clinical trials with iron chelators in patients with cervical carcinoma appear inappropriate.
Simonart
Thierry
T
Department of Dermatology, Erasme University Hospital, Brussels, Belgium. tsimonar@ulb.ac.be
Boelaert
Johan R
JR
Andrei
Graciela
G
Clercq
Erik De
ED
Snoeck
Robert
R
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D000077543:Deferiprone; D003676:Deferoxamine / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D019266:Iron, Dietary / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011728:Pyridones / Q000627:therapeutic use; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000178:diet therapy / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D023041:Xenograft Model Antitumor Assays
D007502:Iron Chelating Agents; D019266:Iron, Dietary; D011728:Pyridones; D000077543:Deferiprone; D003676:Deferoxamine