Digoxin-like immunoreactive factors induced apoptosis in hepatoma and thyroid cancer cell lines

Previously we found that chicken blood contains 10 different species of digoxin-like immunoreactive factors (DLIF) with various molecular weights (Wei et al, Life Sci., 1996). The cytotoxicities of digoxin and that of silica gel column purified DLIF from chicken blood in human hepatoma (SK-hep-1 and Hep G2) and thyroid cancer cell lines (ARO and WRO) were studied in this report. Induction of apoptosis by digoxin and DLIF was time (0-72 hrs) and concentration(0.1-0.001 microM) dependent. The activity of Na⁺,K⁺-ATPase of cancer cells was significantly reduced upon DLIF treatment. A 58 kD Ca⁺⁺-dependent DNase was responsible for the digoxin-induced apoptosis at p53-independent manner and the activity was abrogated by Zn⁺⁺. Digoxin triggered the arrest of hepatoma cells at the G2/M phase, thyroid cells at S phase while chicken DLIF triggered the arrest of hepatoma cells at G0/G1 phase.