Table 1.
Summary of the effects of neurotransmitters on melanoma cells/tumors.
| Factor | Experimental Model | Mechanism | Effect | Reference |
|---|---|---|---|---|
| Catecholamines | ||||
| Norepinephrine | In vitro (C8161, 1174MEL, and Me18105) | Release of VEGF, IL-6, IL-8 | Stimulation of melanoma aggressiveness | [38] |
| In vitro (A375 cells) | Activation of β3-ARs | Recruitment of stromal cells | [73] | |
| Norepinephrine, epinephrine | In vitro (B16F10 melanoma cells) | β-Ars 1-mediated effects | Stimulation of cell proliferation | [17] |
| In vitro (Hs29-4T and A375 cells) | Activation of MAPKs and MMPs 2 and 9 | Stimulation of motility and invasion | [58] | |
| Epinephrine | In vitro (FM-55-P, 92-1, Mel202, and A375 cells) | β2-ARs-mediated effects | Stimulation of cell proliferation and invasion | [59] |
| Epinephrine | In vivo (mice with B16F10 melanoma inoculations) | Mobilization of NK cells and redistribution to tumors in regular exercise | Inhibition of tumor incidence and growth | [96] |
| Phenylephrine | In vitro (SK-Mel 23 cells) | p38 and ERKs signaling via α1-ARs stimulation | Inhibition of cell proliferation | [97] |
| Glutamate | ||||
| Glutamate | In vivo (mice with C8161 xenografts) | Activation of mGlut1 | Stimulation of cell proliferation and metabolic activity | [105] |
| In vivo (mice with UACC903-G4 xenografts) | Activation of PI3K/Akt/mTOR pathway | Stimulation of angiogenesis in xenografts | [110] | |
| Serotonin and Analogs | ||||
| Serotonin | In vitro (B16F10 melanoma cells) | 5-HT2A-mediated cross-talk with SP | Neutralization of the apoptotic effects of SP | [123] |
| Serotonin | In vitro (B16F10, SK-MEL-2, and Melan-A cells) | 5-HT2A-mediated increase in tyrosinase activity, dendritic network, and melanin production | Induction of melanogenesis | [124] |
| 1-NPZ 2 | In vitro (MNT-1 melanoma cells) | Increased expression of Cox-2 and ROS production. | Induction of apoptosis | [130] |
| NCS, NPCS 3 | In vitro (murine B16 and human HMV-II melanoma cells) | Inhibition of tyrosinase | Suppression of melanogenesis | [131] |
| Tegaserod | In vivo (mice with B16F10 melanoma inoculations) | Inhibition of PI3K/Akt/mTOR pathway | Inhibition of tumor growth and dissemination. Increase in survival | [134] |
| Cannabinoids | ||||
| Anandamide | In vitro (A375 melanoma cells) | CB1-mediated induction of caspase-dependent apoptosis; Cox-2 and Lox-mediated cytotoxicity | Induction of apoptosis | [143] |
| THC, WIN 55,212-2 | In vitro (B16 and A375 melanoma cells) | CB1/2-mediated inhibition of Akt signaling inhibition | Induction of apoptosis. Inhibition of cell proliferation and metastasis | [145] |
| Anandamide, ACEA 4 | In vitro (HT168-M1 and WM983B melanoma cells) | CB1-mediated inhibition of PI3K/Akt/mTOR pathway | Inhibition of cell proliferation and metastasis | [147] |
| Cannabidiol | In vivo (mice with B16F10 melanoma inoculations) | Possibly CB2-mediated antitumoral activity | Inhibition of tumor growth. Increased survival and quality of life | [149] |
| WIN 55,212-2 | In vitro (COLO38, SKMEL28, and OCM1A melanoma cells) | Lipid raft-mediated activation of capsase-9 and ERK pathways | Inhibition of cell proliferation | [150] |
| THC, Cannabidiol | In vitro (CHL-1, A375, and SK-MEL-28 melanoma cells) | Atg7-mediated autophagy; TRIB3-mediated apoptosis | Inhibition of cell viability | [151] |
| Cannabis | Human retrospective study | Untested, possibly PD-1 or PD-L1 inhibition | Decrease of immunotherapy (nivolumab) response rate | [153] |
1 ARs = adrenergic receptors; 2 1-NPZ = 1-(1-Naphthyl) piperazine; 3 NCS = N-caffeoylserotonin, NPCS = N-protocatechuoylserotonin; 4 ACEA = Arachidonyl-2-chloroethylamide.