Apoptotic events induced by a natural plastoquinone from the marine alga Desmarestia menziesii in lymphoid neoplasms

Abstract

There exists an urgent need for the development of new drugs for the treatment of lymphoid neoplasms. The aim of this study was to evaluate the cytotoxic effect of the marine plastoquinone 9'-hydroxysargaquinone (9'-HSQ), focusing on investigation of the mechanism by which it causes death in lymphoid neoplastic cells. This particular plastoquinone reduced the cell viability of different hematological tumor cell lines in a time-dependent and concentration-dependent manner. Intrinsic apoptosis occurred with time-dependent reduction of mitochondrial membrane potential (42.3 ± 1.1% of Daudi cells and 18.6 ± 5.6% of Jurkat cells maintained mitochondrial membrane integrity) and apoptosis-inducing factor release (Daudi: 133.3 ± 8.1%, Jurkat: 125.7 ± 6.9%). Extrinsic apoptosis also occurred, as reflected by increased FasR expression (Daudi: 139.5 ± 7.1%, Jurkat: 126.0 ± 1.0%). Decreases were observed in the expression of Ki-67 proliferation marker (Daudi: 67.5 ± 2.5%, Jurkat: 84.3 ± 3.8%), survivin (Daudi: 66.0 ± 9.9%, Jurkat: 63.1 ± 6.0%), and NF-κB (0.7 ± 0.04% in Jurkat cells). Finally, 9'-HSQ was cytotoxic to neoplastic cells from patients with different lymphoid neoplasms (IC_50: 4.9 ± 0.6 to 34.2 ± 0.4 µmol/L). These results provide new information on the apoptotic mechanisms of 9'-HSQ and suggest that it might be a promising alternative for the treatment of lymphoid neoplasms.