Mortality for mammary cancer (MC) has decreased in the past decade, owing principally to early detection and the use of neoadjuvant chemotherapy. Of several preparations that cause regression of MC, Doxorubicin (DOX) is the most active, first-line monotherapeutic. Nevertheless, its use has been limited due to the rapid development of chemoresistance and cardiotoxicity caused by free radicals. In previous studies we have shown that supplementation with moderately high doses of molecular iodine (I2) has a powerful antineoplastic effect in methylnitrosourea (MNU)-induced MC models. These studies also showed a consistent antioxidant effect of I2 in normal and tumoral tissues. In the present study we analyzed the effect of I2 in combination with DOX treatment. Female Sprague Dawley rats with MNU-induced MC were treated with the therapeutic DOX dose (16 mg/kg) and with two lower doses (8 and 4 mg/kg) with and without 0.05% I2 in drinking water. In a first, short-term experiment, iodine treatment began 2 days before a single DOX injection (ip), and the animals were analyzed after 7 days. In a second experiment, animals received two injections (days zero and 14) of 4 mg/kg DOX without or with long-term I2 treatment throughout the 56 days of observation. The results showed that at every DOX dose, short-term I2 treatment induced synergic antineoplastic effects (decreasing tumor size and PCNA signal) with significant protection against body weight loss and cardiotoxicity (CK-MB enzyme and cardiac lipoperoxidation). With long-term I2 treatment, mammary tumors became more sensitive to 4 mg/kg DOX, decreasing chemoresistance markers (Bcl2 and survivin) and increasing peroxisome proliferator-activated receptor type gamma expression, indicating a specific interaction of I2 with these receptors.

The authors thank Felipe Ortóz for his technical assistance and Leonor Casanova for academic supports. Supported in part by PAPIIT/UNAM 201210 and CONACYT 78955.

Citation Format: Carmen Aceves, Yunuen Alfaro-Hernandez, Guadalupe Delgado. Iodine supplement exerts antineoplastic adjuvancy, chemoresistance inhibition and cardioprotection in mammary cancer treatment with anthracyclines. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B38.