Growth-inhibiting effect of crude pineal extracts on human melanoma cellsin vitro is different from that of known synthetic pineal substances

Abstract

The effect was studied of a number of synthetic indoleamines, pteridines, beta-carbolines, of AVT and of crude extracts from rat and ovine pineal glands on human melanoma cells in vitro. The identified pineal substances as well as some of their analogues showed an inhibitory effect only at non-physiologically high concentrations. However, crude pineal extracts were more active than the synthetic pineal substances tested. They contain a compound which may have a tumor-inhibiting potency comparable to that of methotrexate but a different mechanism of action.

Studies of the interactions between melatonin and 2 Hz, 0.3 mT PEMF on the proliferation and invasion of human breast cancer cells

“…Our preliminary studies (data not shown) suggested that the optimal melatonin concentration to inhibit cell growth was 10 À3 M. This concentration level supports the growth inhibition results obtained by Shelard et al [1989] and Bartsch et al [1987]. The results from the cell proliferation studies without the presence of the ®eld are shown in Figure 2a.…”

Partial Purification of a Polypeptide Extract Derived From Ovine Pineal That Suppresses the Growth of Human Melanoma Cells In Vitro

“…In addition, it was shown that a bovine pineal polypeptide extract exerted an antitumour effect on mouse-transplantable tumours [Dilman et al, 19791. These findings are consistent with the reported in vitro tumour cell growth inhibition of ovine pineal substances other than melatonin [Bindoni et al, 1976;Bartsch et al, 1987;Noteborn et al, 1988al. Specifically, administration of an ovine pineal aqueous extract (MW 1,000 to 10,000) delayed the incidence of methylcholanthrene( MCA)-induced sarcomas in mice [Lapin and Ebels, 19761. Interestingly, it has been demonstrated that this pineal extract inhibited the hypophysiotropic activity of male rat and female mice hypothalami in vitro [Ebels et al, 1975;Ebels, 19801. Surprisingly, the same ovine pineal fraction (MW 1,000 to 10,000) reduced the survival time of Wistar rats bearing Yoshida sarcomas, but prolonged the life-span of pinealectomized rats with these tumour implants [Lapin and Ebels, 19761.…”

“…Growth inhibiting activity of pineal fractions was assessed quantitatively by applying a concentration range to the cells. After 4 days, when the controls reached confluence, viable cells were assessed by trypan-blue exclusion, and cell numbers determined with a haemocytometer [Bartsch et al, 1987;Noteborn et al, 1988al.…”

“…Moreover, a reduced urinary excretion of antigonadotropic factors has been observed in patients with cancer of the endometrium, mammary gland, uterine cervix, and prostatic gland [Ostromouva, 1972;Ostromouva et al, 19761. Until now these nonmelatonin ovine pineal substances (MW 1,000 to 10,000) have been incompletely characterized and no information is available about their mode of action. As a first step, this study describes the partial purification of the MW 1,000 to 10,000 polypeptide extract from ovine pineal tissue tested for its ability to inhibit the growth of a melatonin insensitive human melanoma cell strain [Bartsch et al, 1987;Ebels et al, 19881, and that suppressed hypophysiotropic factors [ Ebels et al, 1975;Ebels, 19801.…”

Antitumor Activity of the Pineal Gland: Effect of Unidentified Substances versus the Effect of Melatonin

“…Obviously, the active substance was dissociated from higher molecular weight structures by dilution in water after lyophilization. The chemical nature of this growthinhibiting pineal factor is yet unknown, but it was demon strated that its biological effect and chemical behaviour are different from that of low molecular weight active sub stances known to be present in the pineal gland, including melatonin, its metabolites, (3-carbolines, and pteridines [13,17]. Noteborn et al [13] have been able to purify this extract 1,000-fold, which means that the IC50 values of the purified activity will be in the range of around 10 * M or even lower indicating that the unknown substance is a very potent inhibitor of tumor cell-growth in vitro.…”