Melatonin as a modulator of apoptosis in B-lymphoma cells

Melatonin as a Modulator of Apoptosis in B-Lymphoma Cells Melatonin (N-acetyl-5-methoxy-tryptamine), the major secretory product of the pineal gland, is a lipophilic hormone widely distributed throughout the human body. In addition to playing a role in the regulation of circadian rhythms and seasonal responses, melatonin is involved in many different physiological processes. Melatonin is considered a promising antitumor agent, promoting apoptosis in tumor cells and contrasting it in normal cells. The basis for this selectivity is presumed to be the ability ofmelatonin to stimulate reactive oxygen species (ROS) production in tumor cells. Here we investigate the effect of melatonin on three types of human lymphocytes: normal blood lymphocytes, BL41 Burkitt lymphoma, and the cognate Epstein–Barr virus (EBV)-converted E2r. We found that melatonin promotes ROS production in all these cells. Melatonin protects BL41 from apoptosis in the same manner as normal lymphocytes,whereasE2r are unaffected. These results showthatROSproduction is not limited to tumor lymphocytes nor it is involved in apoptosis promotion; that melatonin does not promote apoptosis in tumor lymphocytes, but EBV inhibits melatonin antiapoptotic effects; and that the anti-apoptotic effect ofmelatonin does not depend on the well-known chemical antioxidant properties of melatonin.