Melatonin inhibits cell proliferation and induces caspase activation and apoptosis in human malignant lymphoid cell lines
Article first published online: 14 MAY 2012
© 2012 John Wiley & Sons A/S
Journal of Pineal Research
Volume 53, Issue 4, pages 366–373, November 2012
How to Cite
Sánchez-Hidalgo, M., Lee, M., de la Lastra, C. A., Guerrero, J. M. and Packham, G. (2012), Melatonin inhibits cell proliferation and induces caspase activation and apoptosis in human malignant lymphoid cell lines. Journal of Pineal Research, 53: 366–373. doi: 10.1111/j.1600-079X.2012.01006.x
- Issue published online: 18 OCT 2012
- Article first published online: 14 MAY 2012
- Accepted manuscript online: 18 APR 2012 01:13PM EST
- Received February 16, 2012; Accepted April 11, 2012.
- caspase activation;
- leukaemia cells;
Abstract: Melatonin exerts strong anti-tumour activity via several mechanisms, including anti-proliferative and pro-apoptotic effects in addition to its potent antioxidant activity. Several studies have investigated the effects of melatonin on haematological malignancies. However, the previous studies investigating lymphoid malignancies have been largely restricted to a single type of malignancy, Burkitt’s lymphoma (BL). Thus, we examined the actions of melatonin on the growth and apoptosis in a small panel of cell lines representing different human lymphoid malignancies including Ramos (Epstein–Barr virus–negative BL), SU-DHL-4 (diffuse large B cell lymphoma), DoHH2 (follicular B non-Hodgkin lymphoma) and JURKAT (acute T cell leukaemia). We showed that melatonin promotes cell cycle arrest and apoptosis in all these cells, although there was marked variations in responses among different cell lines (sensitivity; Ramos/DoHH2 > SU-DHL-4 > JURKAT). Melatonin-induced apoptosis was relatively rapid, with increased caspase 3 and PARP cleavage detected within 0.5–1 h following melatonin addition. Moreover, there was evidence for rapid processing of both caspase 9, as well as a breakdown of the mitochondrial inner transmembrane potential. On the contrary, caspase activation was detected only in SU-DHL-4 and Ramos cells following melatonin treatment suggesting that the extrinsic pathway does not make a consistent contribution to melatonin-induced apoptosis in malignant lymphocytes. Although all cell lines expressed the high-affinity melatonin receptors, MT1 and MT2, melatonin-induced caspase activation appeared to be independent these receptors. Our findings confirm that melatonin could be a potential chemotherapeutic/preventive agent for malignant lymphocytes. However, it is necessary to take into account that different lymphoid malignancies may differ in their response to melatonin.