Melatonin interactions with cultured murine B16 melanoma cells

Ra, Helton; Wa, Harrison; Kelley, Kim; Ma, Kane

doi:10.1097/00008390-199311000-00003

Cited by 24 publications

(23 citation statements)

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“…Accordingly, hamster melanoma cells, which apparently express only the low-affinity receptor, do not show any significant decrease in intracellular CAMP levels reached in response to a variety of stimuli, in the presence of melatonin at concentrations as high as 10 pM (Pickering and Niles, 1992). It should be noted that the occurrence of melatonin-binding sites in B16/F10 mouse melanoma cells has been recently described (Helton et al, 1993). These sites display a Kd of 1.4 nM and might, therefore, correspond to the low-affinity type, i.e.…”

Section: Discussionmentioning

confidence: 75%

Melatonin Antagonizes α‐Melanocyte‐Stimulating Hormone Enhancement of Melanogenesis in Mouse Melanoma Cells by Blocking the Hormone‐Induced Accumulation of the C Locus Tyrosinase

Valverde

Benedito

Solano

et al. 1995

European Journal of Biochemistry

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Melatonin was found to have a small inhibitory effect on tyrosinase activity and a slight stimulatory action on dopachrome tautomerase activity in B16 mouse melanoma cells. These effects were time and dose dependent, with the maximal response being observed after 24-48 h treatment and at concentrations of melatonin higher than the physiologic levels of the circulating hormone. Although these effects on the melanogenic activities were modest, incubation of melanocytes with melatonin prior to the addition of the melanotropin mediated a dramatic inhibition of a-melanocyte-stimulating-hormone-(a-MSH)-induced melanogenesis. This inhibitory effect was evident at melatonin concentrations as low as 10 nM. Inhibition was nearly total at 0.1 mM melatonin, even at high concentrations of a-MSH (1 pM).The inhibitory effect of melatonin on a-MSH stimulation of melanogenesis was investigated. Melatonin appeared to act at least at two stages. Pharmacological concentrations of melatonin diminished the number of a-MSH receptors to about 75% of the control values without an apparent effect on receptor affinity, as determined by receptor-binding studies using '251-[N-Leu4-~-Phe7]a-MSH as a probe. Physiological concentrations of melatonin also appeared to interfere with the intracellular events coupling increased CAMP levels and induction of the c locus tyrosinase, since it strongly inhibited the theophyllinemediated stimulation of melanogenesis. The inhibiton of tyrosinase stimulation was higher in the microsoma1 than in the melanosomal fractions of cells which were treated with melatonin, then exposed to either a-MSH (1 pM) or theophylline (1 mM), suggesting that one of the main effects of melatonin might be inhibition of the induction of tyrosinase de novo synthesis.Keywords : melatonin ; a-melanocyte-stimulating hormone ; tyrosinase ; tyrosinase-related proteins ; melanogenesis.Mammalian pigmentation is the result of melanin production by the epidermal melanocytes. Within melanocytes, melanin synthesis proceeds in specialized organelles, the melanosomes, through a series of coupled enzymic and chemical reactions (reviewed in Prota, 1992). The two initial steps of the pathway, rate-limiting hydroxylation of tyrosine to yield ~-3P-dihydroxyphenylalanine (L-Dopa) and L-Dopa oxidation to L-dopaquinone, are catalyzed by tyrosinase. These two reactions can also be catalyzed, although with lower efficiency, by the tyrosinaserelated protein-1 (TRP1; Jimenez et al., 1991 ; JimCnez-Cervantes et al., 1994) a protein encoded by the b Locus (Jackson, 1988). At least one other enzymic protein, dopachrome tautomerase (Aroca et al., 1990), has been shown to be involved in regulation of the pathway. This enzyme catalyzes the tautomerization of L-dopachrome, the product of spontaneous evolution

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Section: Discussionmentioning

confidence: 75%

Melatonin Antagonizes α‐Melanocyte‐Stimulating Hormone Enhancement of Melanogenesis in Mouse Melanoma Cells by Blocking the Hormone‐Induced Accumulation of the C Locus Tyrosinase

Valverde

Benedito

Solano

et al. 1995

European Journal of Biochemistry

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“…Melatonin has an anti-proliferative function in melanoma cells with either a direct antitumor effect [22]–[25] or through melatonin receptors [26]–[29]. For direct anti-proliferation effects, the effective melatonin dose is 1 μM to 1 mM, and the effective time is 24 to 72 hr.…”

Section: Discussionmentioning

confidence: 99%

“…Melatonin is also reported to induce apoptotic or autophagic cell death [19]–[21]. Numerous studies have demonstrated that melatonin has anti-proliferative effects in melanoma cells [22]–[29], and that these effects are related to the cell line-specific response of melatonin-binding receptors [25]–[29].…”

Section: Introductionmentioning

confidence: 99%

Melatonin Combined with Endoplasmic Reticulum Stress Induces Cell Death via the PI3K/Akt/mTOR Pathway in B16F10 Melanoma Cells

Kim

Yoo

2014

PLoS ONE

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This study investigated B16F10 melanoma cell death induced by melatonin combined with endoplasmic reticulum (ER) stress through the PI3K/Akt/mTOR pathway. Cell viability was significantly decreased after treatment with melatonin combined with ER stress from thapsigargin or tunicamycin compared to no treatment or treatment with melatonin only. Combined melatonin and ER stress also significantly reduced expression of p85β, p-Akt (Ser473, Thr308), and p-mTOR (Ser2448, Ser2481) compared to treatment with melatonin only. The ER stress protein p-PERK and p-eIF2α were significantly increased under combined melatonin and ER stress treatment compared to no treatment or treatment with melatonin only. Combined melatonin and ER stress significantly reduced Bcl-2 protein and augmented Bax protein compared to melatonin-only treatment. Also, the combined treatment significantly lowered expression of catalase, Cu/Zn-SOD, and Mn-SOD proteins compared to melatonin only. Expression of p85β was significantly more decreased under treatment with melatonin and thapsigargin or tunicamycin plus the PI3K inhibitors LY294002 or wortmannin than under treatment with only melatonin or a PI3K inhibitor. The PI3K downstream target p-Akt (Ser473, Thr308) showed significantly decreased expression under treatment with melatonin and thapsigargin or tunicamycin plus PI3K inhibitors than under treatment with melatonin or PI3K inhibitors only. These results indicate that survival of B16F10 melanoma cells after combined treatment with melatonin and ER stress inducers is suppressed through regulation of the PI3K/Akt/mTOR pathway. Melatonin combined with thapsigargin or tunicamycin appears to be a promising strategy for effective melanoma treatment.

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“…Interestingly, the present study has also shown melatonin effectiveness at concentrations as low as 10 -12 M in the SKMEL-188 human melanoma cell line. Also of interest is the slight stimulation of growth in two cell lines (WM-164 and SBCE2) at the melatonin concentration of 10 -9 M, since at the same concentration, a stimulation of 15% was reported in B16 melanoma cells (67).…”

Section: Discussionmentioning

confidence: 99%

Oncostatic effects of the indole melatonin and expression of its cytosolic and nuclear receptors in cultured human melanoma cell lines

Fischer

Żmijewski²,

Zbytek³

et al. 2006

Int J Oncol

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Abstract.Melatonin has been shown to have oncostatic effects on malignant melanoma in vitro and in vivo. We studied the growth suppressive effects of melatonin over a wide range of concentrations in four melanoma cell lines (SBCE2, WM-98, WM-164 and SKMEL-188) representative for different growth stages and phenotype. Melanoma cells were incubated with melatonin 10 -12 -10 -3 M, and proliferation and clonogenicity was assessed at 12 h and 14 days, respectively. We also determined the expression of cytosolic quinone oxidoreductases NQO1, NQO2 (known as MT3 receptor) and nuclear receptor ROR· by RT-PCR. Melatonin at pharmacological concentrations (10 -3 -10 -7 M) suppressed proliferation in all melanoma cell lines. In SKMEL-188 cells cultured in serum-free media, melatonin at low concentrations (10 -12 -10 -10 M) also slightly attenuated the proliferation. The effects of pharmacological doses of melatonin were confirmed in the clonogenic assay. Expression of NQO1 was detected in all cell lines, whereas NQO2 and nuclear receptor ROR· including its isoform ROR·4 were present only in SBCE2, WM-164 and WM-98. Thus, melatonin differentially suppressed proliferation in melanoma cell lines of different behaviour. The intensity of the oncostatic response to melatonin could be related to the cell-line specific pattern of melatonin cellular receptors and cytosolic binding protein expression.

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Melatonin interactions with cultured murine B16 melanoma cells

Cited by 24 publications

References 0 publications

Melatonin Antagonizes α‐Melanocyte‐Stimulating Hormone Enhancement of Melanogenesis in Mouse Melanoma Cells by Blocking the Hormone‐Induced Accumulation of the C Locus Tyrosinase

Melatonin Antagonizes α‐Melanocyte‐Stimulating Hormone Enhancement of Melanogenesis in Mouse Melanoma Cells by Blocking the Hormone‐Induced Accumulation of the C Locus Tyrosinase

Melatonin Combined with Endoplasmic Reticulum Stress Induces Cell Death via the PI3K/Akt/mTOR Pathway in B16F10 Melanoma Cells

Oncostatic effects of the indole melatonin and expression of its cytosolic and nuclear receptors in cultured human melanoma cell lines

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