title: Dietary phytoestrogens present in soy dramatically increase cardiotoxicity in male mice receiving a chemotherapeutic tyrosine kinase inhibitor.
abstract: Use of soy supplements to inhibit cancer cell growth is increasing among patients due to the perception that phytoestrogens in soy inhibit carcinogenesis via induction of apoptosis. Genistein, the most prevalent phytoestrogen in soy, is a potent endocrine disruptor and tyrosine kinase inhibitor (TKI) that causes apoptosis in many cells types. Chemotherapeutic TKIs limit cancer cell growth via the same mechanisms. However, TKIs such as Sunitinib cause cardiotoxicity in a significant number of patients. Molecular interactions between Sunitinib and dietary TKIs like genistein have not been examined in cardiomyocytes. Significant lethality occurred in mice treated with Sunitinib and fed a phytoestrogen-supplemented diet. Isolated cardiomyocytes co-treated with genistein and Sunitinib exhibited additive inhibition of signaling molecules important for normal cardiac function and increased apoptosis compared with Sunitinib alone. Thus, dietary soy supplementation should be avoided during administration of Sunitinib due to exacerbated cardiotoxicity, despite evidence for positive effects in cancer.
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology & BioFrontiers Institute, University of Colorado at Boulder, Boulder, CO 80309, USA.
authors.forename: Pamela Ann
authors.initials: PA
authors.lastname: Harvey
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology & BioFrontiers Institute, University of Colorado at Boulder, Boulder, CO 80309, USA. Electronic address: leslie.leinwand@colorado.edu.
authors.forename: Leslie Anne
authors.initials: LA
authors.lastname: Leinwand
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D054715:Cardiotoxins / Q000009:adverse effects* / Q000494:pharmacology; D007211:Indoles / Q000009:adverse effects* / Q000494:pharmacology; D008297:Male; D051379:Mice; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D048789:Phytoestrogens / Q000737:chemistry / Q000633:toxicity*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000494:pharmacology; D011758:Pyrroles / Q000009:adverse effects* / Q000494:pharmacology; D013025:Glycine max / Q000737:chemistry*; D000077210:Sunitinib
chemical_list: D000970:Antineoplastic Agents; D054715:Cardiotoxins; D007211:Indoles; D048789:Phytoestrogens; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D000077210:Sunitinib
keywords: Cardiotoxicity; Genistein; Sunitinib; Tyrosine kinase inhibitors