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¹ Department of Physiology, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland² Department of Pediatrics, University of Turku, 20520 Turku, Finland³ Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-714 Olsztyn, Poland⁴ Department of Reproductive Biology, Imperial College London, London W12 ONN, UK

(Correspondence should be addressed to N A Rahman; Email: nafis.rahman{at}utu.fi)

Novel strategies are needed for the treatment of adrenocortical tumors that are usually resistant to chemotherapy. Hecate, a 23-amino acid lytic peptide, was conjugated to the 15-amino acid (81–95) fragment of the human chorionic gonadotropin β (CGβ) chain, which would selectively kill cancer cells expressing the LH receptor (LHR) sparing the normal ones with LHR. To prove the principle that Hecate-CGβ conjugate may eradicate tumors ectopically expressing plasma membrane receptors, transgenic (TG) inhibin -subunit promoter (inh)/Simian Virus 40 T-antigen mice, expressing LHR in their adrenal gland tumors, were used as the experimental model. Wild-type control littermates and TG mice with adrenal tumors were treated with either Hecate or Hecate-CGβ conjugate at the age of 6.5 months for 3 weeks and killed 7 days after the last treatment. The Hecate-CGβ conjugate reduced the adrenal tumor burden significantly in TG male but not in female mice, in comparison with Hecate-treated mice. Hecate-CGβ conjugate treatment did not affect normal adrenocortical function as the serum corticosterone level between Hecate and Hecate-CGβ conjugate groups were similar. The mRNA and protein expressions of GATA-4 and LHR colocalized only in tumor area, and a significant downregulation of gene expression was found after the Hecate-CGβ conjugate in comparison with Hecate- and/or non-treated adrenal tumors by western blotting. This finding provides evidence for a selective destruction of the tumor cells by the Hecate-CGβ conjugate. Hereby, our findings support the principle that Hecate-CGβ conjugate is able to specifically destroy tumor cells that ectopically express LHR.