IC50: 19 μM – 60 μM for various ovarian cancer cell lines
Bithionol is a potent inhibitor of soluble adenylyl cyclase (sAC).
Adenylyl cyclase is an enzyme with critical regulatory roles in cells. All classes of adenylyl cyclases can catalyse the conversion of adenosine triphosphate to 3',5'-cyclic AMP and pyrophosphate.
In vitro: Bithionol could cause dose-dependent cytotoxicity toward all tested ovarian cancer cell lines regardless of their sensitivities to cisplatin. Moreover, such cell death appeared to be via caspases mediated apoptosis. In addition, the mechanism of action appeared to be partially by cell cycle arrest, ROS generation as well as ATX inhibition [1].
In vivo: Oral toxicity of bithionol sulfoxide was assessed in acute toxicity studies in mice and rats. The median lethal dose (LD50) values in mice were > 1000 mg/kg and < 5000 mg/kg after 21 days; the male rat LD50 value was around 5000 mg/kg after 48 h. Moreover, the hepatic toxicity was observed at all tested doses. Increases in serum AST were observed with the high doses, suggesting that mitochondria were affected. In addition, the histological study indicated more intense periportal fatty infiltration with high doses at 5000 and 500 mg/kg [2].
Clinical trial: In a previous study, bithionol was orally given to patients with acute fascioliasis at the daily dose of 25 mg/kg for 10 days. Results showed that all patients were cured. The follow-up period after the first course of treatment was between 16 and 47 months and no major side effects were found [3].
References:
[1] Ayyagari VN,Brard L. Bithionol inhibits ovarian cancer cell growth in vitro - studies on mechanism(s) of action. BMC Cancer.2014 Feb 4;14:61.
[2] Lavric A, Skubic V, Senk L, Lukanc G, Kacl E. Oral toxicity of bithionol sulfoxide in mice and rats. Zbornik Veterinarske Fakultete Univerza Ljubljana 1990 27(1): 33-39
[3] Bacq Y,Besnier JM,Duong TH,Pavie G,Metman EH,Choutet P. Successful treatment of acute fascioliasis with bithionol. Hepatology.1991 Dec;14(6):1066-9.