We have investigated the effect of melatonin on cell proliferation and modulation, in the GH3 experimental rat pituitary cell line; the expression of oncogenes c-myc, c-jun and the tumor suppressor gene p53 were also analyzed basally and after exposure to melatonin (10–6, 10–8 and 10–10 M). Melatonin exhibited an antiproliferative effect at all the doses tested, decreasing the proliferating index by 50%. After exposure to melatonin, a decrease in Ki67 and Proliferation cell nuclear antigen occurred acute- and transiently (at 2 h) after a single dose which recovered at 4 h, as well as chronically after repeated 12-hour doses which persisted at 48 h; a similar behavior was observed both acute- and chronically for c-myc and c-jun, while it was opposite for p53, rising acute- and transiently as well as after repeated exposure. These results demonstrate that melatonin modulates the proliferation mechanisms of the GH3 cells.

1.
Reiter RJ: The pineal gland and its hormones in the control of reproduction in mammals. Endocrine Rev 1980;1:109–131.
2.
Cassone V: Effects of melatonin on vertebrate circadian systems. Trends Neurosci 1990;13:457–464.
3.
Arendt J: Role of the pineal gland in seasonal reproductive function in mammals. Oxford Rev Reprod Biol 1986;8:266–320.
4.
Webb SM, Puig-Domingo M: Role of melatonin in health and disease. Clin Endocrinol 1995;42:221–234.
5.
Tan D-X, Chen L-D, Poeggeler B, Manchester LC, Reiter RJ: Melatonin: A potent endogenous hydroxyl radical scavenger. Endocrine J 1993;1:57–60.
6.
Sainz RM, Mayo JC, Uría H, Kotler M, Antolín I, Rodríguez C, Menéndez-Peláez A: The pineal neurohormone melatonin prevents in vivo and in vitro apoptosis in thymocytes. J Pineal Res 1995;19:178–188.
7.
Brzezinski A: Melatonin in humans. N Engl J Med 1997;336:186–195.
8.
Hill SM, Blask DE: Effects of the pineal hormone melatonin on the proliferation and morphological characteristics of human breast cancer cells (MCF-7) in culture. Cancer Res 1988;48:6121–6126.
9.
Fornas O, Mato ME, Ortiz MA, Webb SM: Modulation of cell proliferation by melatonin in the RINm5F cell line; in Webb SM, Puig-Domingo M, Möller M, Pévet P (eds): Pineal Update; from Molecular Mechanisms to Clinical Implications. Westbury, PJD Publications Limited, 1997, pp 383–388.
10.
Hollstein M, Sidransky D, Vogelstein B, Harris CC: p53 mutations in human cancers. Science 1991;253:49–53.
11.
Monternarh M: Biochemical properties of the growth suppressor/oncoprotein p53. Oncogene 1992;7:1673–1680.
12.
Tashjian AH, Yasumura Y, Levine L, Sato GH, Parker ML: Establishment of clonal strains of rat pituitary tumor cells that secrete growth hormone. Endocrinology 1968;82:342–352.
13.
Tamarkin L, Cohen M, Roselle AD, Reichert C, Lippman M, Chabner B: Melatonin inhibition and pinealectomy enhancement of 7,12-dimethyl-benz(a)anthracene-induced mammary tumors in the rat. Cancer Res 1981;41:4432–4436.
14.
Ying SW, Niles LP, Crocker C: Human malignant melanoma cells express high-affinity receptors for melatonin: Antiproliferative effects of melatonin and 6-chloromelatonin. Eur J Pharmacol 1993;246:89–96.
15.
Pardee AB: G1 events and regulation of cell proliferation. Science 1989;246:603–608.
16.
Caelles C, Helmberg A, Karin M: p53 dependent apoptosis in the absence of transcriptional activation of p53-target genes. Nature 1994;370:220–223.
17.
Levine AJ, Mommand J, Finlay CA: The p53 tumor suppressor gene. Nature 1991;370:453–456.
18.
Mediavilla MD, Cos S, Sánchez-Barceló EJ: Melatonin increases p53 and p21WAF1 expression in MCF-7 human breast cancer cells in vitro. Life Sci 1999;65:415–420.
19.
Vanecek J: Cellular mechanisms of melatonin action. Physiol Rev 1998;3:687–721.
20.
Sassone-Corsi P: Coupling gene expression to cAMP signaling: Role of CREB and CREM. Int J Biochem Cell Biol 1998;1:27–38.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.