Selenium-containing compounds and D-panthetine modulate the action of doxorubicin and cisplatin towards drug-resistant tumor cells

Abstract

The aim of this work was to study biological activity of sodium selenite, selenomethionine and D-panthetine towards drug-resistant human leukemia and carcinoma cells, characterized by overexpression of P-glycoprotein and knockout of Bax gene which plays a key role in the induction of cell death. It was found that sodium selenite possessed a pronounced cytotoxic effect on tumor cells already at 10 µM concentration, whereas selenomethionine was much less toxic (active concentration 100 µM) and D-panthetine (vitamin B5 derivative) showed antitumor activity in 100–1000 µM concentration range depending on the studied cell lines. Studies of anticancer activity of these antioxidants (in physiologically harmless concentrations) in combination with semilethal (LC50) dose of anticancer drugs – cisp­latin and doxorubicin – revealed that all compounds enhanced cytotoxic activity of cisplatin, with most pronounced effect towards drug-resistant cells. Thus, the combined effect of cisplatin and antioxidants significantly enhanced the cytofoxic effect of that drug towards drug-resistant tumor cells. Sodium selenite in low concentrations inhibited cytofoxic action of doxorubicin by 20–25%. That effect was accompanied by a complete inhibition of production of toxic superoxide radicals induced by doxorubicin. We suggest that such ROS-inhibiting effect of sodium selenite might be important in protecting normal cells (e.g., cardiomyocytes) from toxic effects of doxorubicin.

Keywords

• antioxidants
• anticancer drugs
• reactive oxygen species
• selenomethio­nine
• sodium selenite
• d-panthetine