Antiandrogenic effect of crude extract of C-heavy oil

Abstract

An oil spill accident happened to a Russian tanker Nakhodka with a cargo of heavy oil type C in the Sea of Japan on January, 1997 and the spilled oil severely polluted the coast of Japan and damaged the environment. In this study, androgenic and antiandrogenic activities of C-heavy oil crude extracts prepared with ethanol were evaluated on two androgen-responsive cell lines, a Shionogi mouse mammary carcinoma SC115 and a human prostate carcinoma LNCaP. Oils used in this study were the Nakhodka and a commercial C-heavy oils. Assessment of androgenic and antiandrogenic activities was made on the basis of effect on proliferation (SC115) and prostate specific antigen (PSA) production (LNCaP cells) in the absence and the presence of 0.5 nM dihydrotestosterone (DHT). While both extracts exerted almost no effect on the proliferation and PSA production of SC115 and LNCaP cells in the absence of DHT, the extracts significantly inhibited the DHT-induced proliferation and PSA production of the cells in the presence of DHT, indicating that the C-heavy oils contains antiandrogenic compounds. It has been known that androgen receptor (AR) expressed in LNCaP cells has mutation in ligand-binding domain and consequently, its transcription promoting action after ligand-binding is different from that of normal AR. Cyproterone acetate (CA), an androgen antagonist, and 17β-estradiol, an estrogen, stimulated PSA production and their stimulatory effects were additive to that of DHT in LNCaP cells, while CA inhibited DHT-induced proliferation and 17β-estradiol showed quite weak agonistic effect in SC115 cells. Therefore, a part of antiandrogenic effects of the oil extracts was considered to be mediated through mechanism other than direct transcriptional activation by activated AR. Then, a few polycyclic aromatic hydrocarbons (PAHs) that are considered not to bind to AR were examined for their androgenic and antiandrogenic effect. Benzo[ a]anthracene (BaA), benzo[ k]fluoranthene (BkF) and benzo[ a]pyrene (BaP) suppressed DHT-induced proliferation and PSA production of SC115 and LNCaP cells in a concentration-dependent manner. The antiandrogenic effect of the two heavy oil extracts was considered to be due in part to PAHs.