Effect of melatonin and pineal extracts on human ovarian and mammary tumorcells in a chemosensitivity assay

Pinealectomy enhances turner growth and metastatic spread in experimental a nimals. This effect is only in part due to melatonin since melatonin-free p ineal extracts containing yet unidentified pineal substances have also show n tumor inhibiting activity. Despite numerous reports suggesting melatonin as a potential anti-cancer agent there have not been sufficient clinical tr ials to define the actual therapeutic potential of melatonin for the treatm ent of human cancers; To help fill this gap, we used a chemosensitivity ass ay designed to test the sensitivity of tumors from individual patients towa rds chemotherapeutic drugs for assessing the effect of melatonin and pineal extracts on primary human tumor cells. Primary cell cultures from seven ov arian and six mammary tumors were incubated with melatonin, the pineal extr act YC05R (containing substances between 500 and 1000 daltons) and chemothe rapeutic drugs. The pineal extract YC05R inhibited growth of all tumors in a dose-dependent manner. Physiological concentrations of melatonin (10(-8)- 10(-10) M) inhibited the growth of one out of six mammary carcinomas in a d ose-dependent manner. Primary cell cultures from three ovarian tumors were affected by melatonin in different ways, i.e,, two were inhibited and one w as slightly stimulated. There was no correlation between sensitivity toward s melatonin and sex steroid receptor status, stage or grade of the tumor, I t is concluded that, I), melatonin may be an inhibitor of human mammary and ovarian carcinoma in individual cases and, 2), the pineal gland contains v ery active anti-tumor substances inhibiting both, the mammary and ovarian t umors, tested. These substances require chemical and biological identificat ion, (C) 2000 Elsevier Science Inc. All rights reserved.