Melatonin has no effect on the growth, morphology or cell cycle of human breast cancer (MCF-7), cervical cancer (HeLa), osteosarcoma (MG-63) or lymphoblastoid (TK6) cells

Panzer, Annie; Lottering, Mona-Liza; Bianchi, Pepita; Glencross, Deborah K.; Stark, J. H.; Seegers, J.C.

doi:10.1016/s0304-3835(97)00360-1

Cited by 48 publications

(39 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although some (Irani et al, 1997;Joneson and Bar-Sagi, 1998) have claimed that other antioxidants, such as N-acetyl-lcysteine (NAC) and superoxide dismutase (SOD), can inhibit the mitogenic activity in ras-transformed cells, this is first report that melatonin can block ras-induced cell growth, which provides a new insight for its oncostatic ability. Accumulated reports (Panzer et al, 1998;Cos and Sanchez-Barcelo, 2000;Marelli et al, 2000) showing that melatonin exerts oncostatic action that make it a potential supplement in the treatment of various cancers in vitro, in vivo, and in clinical therapy further support our hypothesis. Melatonin inhibits MCF-7 human breast cancer cell proliferation by inducing a G0/G1 arrest, which is dependent on an increased expression of p21WAF1 protein (Mediavilla et al, 1999).…”

Section: Discussionsupporting

confidence: 75%

Glutathione depletion-induced apoptosis of Ha-ras-transformed NIH3T3 cells can be prevented by melatonin

2003

View full text Add to dashboard Cite

It is well known that intracellular antioxidant glutathione (GSH) plays major roles in the maintenance of redox status and defense of oxidative stress. Ras, a small GTPbinding protein, may send growth-stimulating message to the nucleus through downstream Rac oncoprotein and superoxide (O 2 À ). These findings led us to investigate the effects of GSH and melatonin, a free-radical scavenger, on Ras-Rac-O 2 À -related growth signal transduction. Our results demonstrate that overexpression of the inducible Ha-ras oncogene by isopropyl-b-d-thiogalactoside (IPTG) increases the levels of reactive oxygen species (ROS, including O 2 À and hydrogen peroxide (H 2 O 2 )) and GSH in an Ha-ras-transformed NIH/3T3 fibroblast cell line. On the contrary, melatonin significantly suppresses ras-triggered cell growth by inhibiting the increase of ROS and GSH. Moreover, severe apoptosis of this transformed cell line occurred when the cell redox balance between ROS and GSH was dramatically changed in the presence of IPTG and l-buthionine-[S,R]-sulfoximine (BSO, a specific inhibitor of GSH synthetase). That BSO-induced cell apoptosis needs Ras to increase the ROS level was demonstrated by the free-radical scavenger melatonin. It effectively blocked cell apoptosis, but cell growth was also slowed without affecting Ras expression. Based on our studies, two approaches can be applied to treating ras-related cancers. One is utilizing melatonin to suppress cancer cell proliferation, and the other is utilizing BSO to induce cancer-cell apoptosis. Cotreatment of rasrelated cancer cells with melatonin and BSO stops cell growth as well as apoptosis. Whether these cancer cells will undergo further regression or become recurrent merits investigation.

show abstract

Section: Discussionsupporting

confidence: 75%

Glutathione depletion-induced apoptosis of Ha-ras-transformed NIH3T3 cells can be prevented by melatonin

2003

View full text Add to dashboard Cite

show abstract

“…It is believed that the potential anticancer actions of melatonin [25] are mediated through immunostimulatory [26,27], free radical scavenger [28,29], and direct antiproliferative effects of the hormone. Of note, the majority of scienti®c evidence supports a direct oncostatic effect of melatonin on different types of cancer cells by its antiproliferative action [30±35], albeit with occasional inconsistent or controversial results [36,37]. While melatonin was reported to inhibit, in vitro, the proliferation of androgen-insensitive PC-3 prostate cancer cells at high cell density [14], it was particularly signi®cant when three research teams, including our group, demonstrated independently the inhibition of proliferation of androgen-sensitive LNCaP prostate cancer cells in vitro [11±13].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of androgen-sensitive LNCaP prostate cancer growth in vivo by melatonin: Association of antiproliferative action of the pineal hormone with mt1 receptor protein expression

Siu

Fong

et al. 2001

Prostate

View full text Add to dashboard Cite

“…Today, many of the oncostatic properties of melatonin have been fairly well described (Vijayalaxmi et al, 2002), and evidence from experimental studies strongly suggests a link between melatonin and tumour suppression (Schernhammer and Hankinson, 2003). In vitro studies, although not entirely consistent (Panzer et al, 1998), give support to a reduction in the growth of malignant cells of the breast (Hill and Blask, 1988;Cos et al, 1996Cos et al, , 1998Cos et al, , 2002Mediavilla et al, 1999) and other tumour sites (Sze et al, 1993;Ying et al, 1993;Petranka et al, 1999;Shiu et al, 1999;Kanishi et al, 2000) by both pharmacological and physiologic doses of melatonin. In rodent models, pinealectomy boosts tumour growth (Tamarkin et al, 1981), whereas exogenous melatonin administration exerts anti-initiating (Musatov et al, 1999) and oncostatic activity (Anisimov et al, 1997Cini et al, 1998;Mocchegiani et al, 1999) in various chemically induced cancers.…”

Section: Cancer-protective Effects Of Melatoninmentioning

confidence: 99%

Melatonin and cancer risk: does light at night compromise physiologic cancer protection by lowering serum melatonin levels?

2004

View full text Add to dashboard Cite

The suprachiasmatic nuclei in the hypothalamus, one of the most important physiological determinants of alertness and performance, drive a circadian pacemaker in mammals, with an intrinsic period averaging 24 h. Light is the primary stimulus to the disruption and resetting of this pacemaker, which is expressed in changing melatonin rhythms. Melatonin production in humans decreases when people are exposed to light at night. Since melatonin shows potential oncostatic action in a variety of tumours, it is possible that lowered serum melatonin levels caused by exposure to light at night enhance the general tumour development. Cancer is the second leading cause of death in industrialised countries like the United States, where a significant proportion of workers engage in shift work, making a hypothesised relation between light exposure at night and cancer risk relevant. Observational studies support an association between night work and cancer risk. We hypothesise that the potential primary culprit for this observed association is the lack of melatonin, a cancer-protective agent whose production is severely diminished in people exposed to light at night.

show abstract

Melatonin has no effect on the growth, morphology or cell cycle of human breast cancer (MCF-7), cervical cancer (HeLa), osteosarcoma (MG-63) or lymphoblastoid (TK6) cells

Cited by 48 publications

References 20 publications

Glutathione depletion-induced apoptosis of Ha-ras-transformed NIH3T3 cells can be prevented by melatonin

Glutathione depletion-induced apoptosis of Ha-ras-transformed NIH3T3 cells can be prevented by melatonin

Inhibition of androgen-sensitive LNCaP prostate cancer growth in vivo by melatonin: Association of antiproliferative action of the pineal hormone with mt1 receptor protein expression

Melatonin and cancer risk: does light at night compromise physiologic cancer protection by lowering serum melatonin levels?

Contact Info

Product

Resources

About