Effect of melatonin and pineal extracts on human ovarian and mammary tumor cells in a chemosensitivity assay.

Pinealectomy enhances tumor growth and metastatic spread in experimental animals. This effect is only in part due to melatonin since melatonin-free pineal extracts containing yet unidentified pineal substances have also shown tumor inhibiting activity. Despite numerous reports suggesting melatonin as a potential anti-cancer agent there have not been sufficient clinical trials to define the actual therapeutic potential of melatonin for the treatment of human cancers. To help fill this gap, we used a chemosensitivity assay designed to test the sensitivity of tumors from individual patients towards chemotherapeutic drugs for assessing the effect of melatonin and pineal extracts on primary human tumor cells. Primary cell cultures from seven ovarian and six mammary tumors were incubated with melatonin, the pineal extract YC05R (containing substances between 500 and 1000 daltons) and chemotherapeutic 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 dose-dependent manner. Primary cell cultures from three ovarian tumors were affected by melatonin in different ways, i.e., two were inhibited and one was slightly stimulated. There was no correlation between sensitivity towards melatonin and sex steroid receptor status, stage or grade of the tumor. It is concluded that, 1), melatonin may be an inhibitor of human mammary and ovarian carcinoma in individual cases and, 2), the pineal gland contains very active anti-tumor substances inhibiting both, the mammary and ovarian tumors, tested. These substances require chemical and biological identification.