From: Melatonin and urological cancers: a new therapeutic approach
Melatonin dose or concentration | Targets | Effects | Model | Cell line | Refs |
---|---|---|---|---|---|
1 pM, 1 nM, 1 μM, 1 mM | mTOR, ERK1/2, Akt, OXPHOS, ROS | Anti-proliferative and antioxidant effects | In vitro | PNT1A | [55] |
UCM 1037 (analogue) | Androgen receptor, Akt | Anti-proliferative and cytotoxic effects against cancer cells | In vitro | LNCaP, PC3, DU145, 22Rv1 | [76] |
1 mM | Pentose phosphate pathway | Decreased LDH activity, tricarboxylic acid cycle, ATP/AMP ratio, glucose uptake, and lactate labeling Limited glycolysis | In vitro | LNCaP , PC-3 | [77] |
3 mg/kg | Nrf2, HIF-1α | Inhibited tumor growth | In vivo | LNCaP | [63] |
10− 6 M | NF-κB, AR-V7, IL-6, | Delayed castration resistance development | In vitro | LNCaP, 22Rv1 | [61] |
200 µg/ml 50 µM–1 mM | MAPK/ERK, IGFBP3 | Increased survival time of TRAMP mice when administered at the initiation or advanced stages | In vivo, in vitro | LNCaP | [53] |
10 µg/kg 500 µM, 5 mM, 10 mM | Androgen receptor (AR), PCNA, MTR1B | proliferative and anti-apoptotic effects in prostate cells subjected to HG levels | In vivo, in vitro | PNTA1, PC-3 | [78] |
1 mM | VEGF, HIF-1α, HIF-2α, miR-3195, miR-374b | Anti-angiogenic activity | In vitro | PC-3 | [59] |
1 mg/kg | Nrf2, Ki67, HIF-1α, Akt | Inhibited cancer growth and exerted anti-angiogenic effects | In vivo | LNCaP | [57] |
10− 8 M | p27, NF-κB, MT1, | Anti-proliferative effects | In vitro | LNCaP, 22Rv1 | [79] |
1 mM | TRAIL, TNF-α | Promotes cell toxicity and cancer cell death, inhibited oxidative stress, and suppressed cancer cell proliferation | In vitro | LNCaP, PC-3 | [62] |
10 mg/kg | GSH, MDA, SOD | Inhibited tumor growth and oxidative stress | In vivo | – | [80] |
10− 11-10− 5 M | MT1, p27, AR | Anti-proliferative effects | In vitro | RWPE-1, 22Rv1, VCaP, LNCaP | [81] |
1 mM | Akt/GSK-3β, HIF-1α, SPHK1, VEGF, von Hippel-Lindau | Antioxidant effects | In vitro | PC-3 | [82] |
100 nM–2 mM | Sirt1, IGF-1)/IGFBP3, PCNA, Ki-67 | Anti-proliferative effects Inhibited tumorigenesis | In vivo, in vitro | PC-3, DU145, 22Rν1, LNCaP | [56] |
100 µM, 1 mM, 2mM | Per2, Clock, Bmal1 | Anti-proliferative effects Caused a resynchronization of oscillatory circadian rhythm genes | In vitro | PC-3, DU145, 22Rν1, LNCaP | [83] |
10− 8-10− 3 M | – | Inhibited viability and induced apoptosis | In vitro | PC-3, DU145, 22Rν1, LNCaP | [84] |
1 mM | HIF-1α, | Anti-angiogenic effect | In vitro | PC-3, DU145, LNCaP | [58] |
0–3 mM | p38, JNK | Induced apoptosis Inhibited cancer cell growth | In vitro | LNCaP | [54] |
10− 9, 10− 8, 10− 7 | PKA, PKC, p27, MT1 | Anti-proliferative effects | In vitro | 22Rv1 | [85] |
10− 11, 10− 5 | p27, PKA, PKC, MT1, androgen signaling | Anti-proliferative effects | In vitro | 22Rv1 | [86] |
0.5, 1 mM | – | Induced cell cycle arrest and cellular differentiation Inhibited proliferation of cancer cells | In vitro | LNCaP, PC-3, | [87] |
5 mg | MT1 | Anti-proliferative effects Induced stabilization of patient’s hormone-refractory disease | Human | – | [88] |
4 µg/g | EGF, Cyclin D1 | Inhibited tumor growth and proliferation | In vivo | PC-3, DU145, LNCaP | [89] |
– | – | AR activity attenuation by melatonin is not due to inhibition of AR binding to the androgen responsive element (ARE) | In vitro | LNCaP, PC-3 | [90] |
4 µg/g | MT1 | Anti-proliferative effects | In vivo | PC-3, LNCaP | [91] |
0.01–100 nM | cAMP | suppressed cancer cell proliferation and induced cell cycle arrest | In vitro | DU145 | [92] |
5 × 10−11-5 × 10 −5 | MT1, sex steroid-mediated calcium influx | Anti-proliferative effects | In vitro | LNCaP | [93] |
0.01–1000 nM | Mel1a receptor | Anti-proliferative effects | In vitro | LNCaP | [94] |
20 mg | IGF-1, PRL | Combination therapy with triptorelin and melatonin decreased PSA mean concentrations Melatonin reversed clinical resistance to LHRH analogue triptorelin in metastatic prostate cancer | Human | – | [95] |
50 µg | – | Inhibited tumor growth | In vivo | Dunning R-3327-HIF tumor | [96] |