An Insight into Neuropeptides Inhibitors in the Biology of Colorectal Cancer: Opportunity and Translational Perspectives
Abstract
:1. Introduction
2. Most Significant Neurotransmitters in Cancer Development and Progression
3. Neuropeptides: Peptidergic Neurotransmitters
4. Promising Neuropeptides Inhibitors for the Development of Effective Cancer Therapy
4.1. Emerging Neuropeptides Inhibitors in Colorectal Cancer
4.1.1. Bombesin
4.1.2. Neurotensin
4.1.3. Vasoactive Intestinal Peptide
4.1.4. Substance P
4.1.5. Neuropeptide Y
4.1.6. Orexins
4.2. Neuropeptides Inhibitors: A Promising Approach also for Other Cancers
4.2.1. Breast Cancer
4.2.2. Prostate Cancer
4.2.3. Glioblastoma
4.2.4. Lung Cancer
5. Conclusions and Future Perspectives
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Neurotransmitters | Sources | Expressed | Description | Refs. |
---|---|---|---|---|
Peptidergic neuropeptides | ||||
Neurotensin (C78H121N21O20) | Hypothalamus and intestine | Hypothalamus, bronchial epithelial cell, lymph node, anterior pituitary, jejunal mucosa, superficial temporal artery, hippocampus proper, duodenum, appendix and gallbladder. | Neurotensin is thought to regulate the luteinizing hormone, prolactin release and brain dopamine system. Involved in a wide variety of biological effects, such as histamine release, vasodilation, gastrointestinal (GI) muscle modulation and motility, and stimulation of intestinal secretion. | [3,4] |
Vasoactive intestinal polypeptide | Gut, pancreas, and hypothalamus | Appendix, rectum, gastric mucosa, endothelial cell, transverse colon, cingulate gyrus and prefrontal cortex | It performs several functions in the body, such as relaxation of muscle in digestive tract and heart, control of fluid secretion, increase in glycogenolysis and reduction of the blood pressure. | [5,6] |
Substance P (C63H98N18O13S) | Brain, spinal cord and intestine | Hypothalamus, amygdala and periaqueductal gray | Substance P is associated with inflammation, pain, anxiety, mood, cell migration and angiogenesis. | [7,8] |
Bombesin (C71H110N24O18S) | Brain | - | It mediates gastrin release and was also termed gastrin-releasing peptide. It participates in various processes, such as glucose homeostasis, circadian rhythm, thermoregulation, and many GI processes. | [9,10] |
Neuropeptide Y (C190H287N55O57) | Brain and circulating platelets | Cerebral cortex, thalamus, brainstem, hypothalamus, amygdala, prostate, and hippocampus | Neuropeptide Y plays a crucial role in food intake, reducing stress and pain, lowering blood pressure, and storing of energy. | [11,12] |
Calcitonin gene-related peptide (CGRP) | Peripheral and central neuron | placental syncytiotrophoblast, villous vascular endothelial cells, and decidua | Calcitonin gene-related peptide is implicated in vasodilation, appetite suppression, stem cell mobilization, and homeostasis. | [13,14] |
Biogenic neurotransmitter | ||||
Dopamine (C8H11NO2) | Substantia nigra ventral brain | Brain, blood vessels, kidneys, pancreas, and gastrointestinal tract | Dopamine regulates norepinephrine inhibition, vasodilation, increases sodium excretion, reduces insulin production and gastrointestinal motility. | [15,16] |
Epinephrine and Norepinephrine (C9H13NO3) | Adrenal gland and medulla oblongata | Heart, liver, lungs, muscles, and brain | Epinephrine has effects on increasing blood sugar, heart rate, smooth muscle contraction, and pupil dilation | [17,18] |
Serotonin (C₁₀H₁₂N₂O) | Enteric nervous system located in the GI tract and brain | - | Sleep, emotion, mood, wound healing, immune regulation, and insulin secretion are some of the important cognitive and peripheral functions modulated by serotonin. | [19,20] |
Acetylcholine (Ach, C7NH16O2+) | Motor neurons, parasympathetic nervous system and brain | Skeleton muscle, brain, and other organs | Ach is a well-known neurotransmitter of the neuronal system, it is also synthesized in non-neuronal cells including mesothelial, adipocytes, fibroblast, epithelial, endothelial, and cancer cells. | [21,22] |
Amino acids | ||||
Gamma-aminobutyric acid-GABA, (C4H9NO2) | Brain | - | GABA is an inhibitory neurotransmitter that blocks messages or nerve signals between nerves and CNS, though its function is well defined in reducing the feeling of stress, anxiety, and fear. | [23,24] |
Glycine (C₂H₅NO₂) | Kidneys and liver | - | Glycine is an inhibitory neurotransmitter of the central nervous system CNS, produced naturally in the body and important for the healthy development of bones, muscles, and tissues. | [25] |
Histamine (C5H9N3) | Basophils and mast cells | - | It plays a central role in inflammatory response and as itching mediator. | [26] |
Neuropeptides | Number of Amino Acids | Discovery | Related Cancers | Tumorigenic Properties | Refs. |
---|---|---|---|---|---|
Neurotensin | 13 | Carraway and Leeman in 1973 | Pancreatic, lung, breast, prostate, and colorectal cancer | Increased cell proliferation and migration | [86,87] |
Vasoactive intestinal polypeptide (VIP) | 28 | Said and Mutt in 1970 | Neuroblastoma, pituitary adenomas, colorectal cancer, endometrial, and lung cancer | Increased cell proliferation, metastasis, invasion, and angiogenesis | [88,89] |
Substance P | 11 | Von Euler and Gaddum in 1931 | Glioblastoma, breast, acute lymphoblastic Leukemia, colorectal cancer, melanoma, and gastric cancer | Increased cell proliferation, migration, invasion, and angiogenesis; pro-inflammatory effect | [90,91] |
Bombesin | 14 | Battey and Wada in 1991 | Prostate, gastric, lung, breast, colorectal cancer, renal cell carcinoma, small cell lung carcinoma, neuroendocrine, squamous, colon, and pituitary cancer | Promoted vascularization, tumor growth, and differentiation | [92,93,94,95] |
Neuropeptide Y | 36 | Tatemoto and Mutt in 1982 | Neuroblastoma, colorectal cancer, breast, Ewing sarcoma, and prostate cancer | Induced cell growth, vascularization, and angiogenesis; pro-inflammatory effect | [46,96,97] |
Calcitonin gene-related peptide (CGRP) | 37 | Amara and colleagues in 1982 | Prostate, lung, colorectal cancer, pancreatic, ovarian, endometrial, pituitary, renal, and hepatic cancer | Promoted angiogenesis, lymphangiogenesis, cell growth, neovascularization, proliferation, and migration | [98,99,100,101] |
Neuropeptide | Cancer | Drugs/Antagonists | Targeted Receptors | Refs. |
---|---|---|---|---|
Bombesin (neuromedin B/gastrin-releasing peptide) | Small cell lung carcinoma | PD176252, PD168368 | Gastrin-releasing peptide receptors-GRPR, neuromedin B receptor-NMBR | [169,170] |
Bantag-1 | Bombesin-receptor subtype-3 | |||
Breast | RC-3095, RC-3940-II | Gastrin-releasing peptide receptors-GRPR | [92,171,172] | |
CRC | RC-3095, AN-215 | Gastrin-releasing peptide receptors-GRPR | [121,154] | |
Prostate | BAY 86-7548, 64Cu-CB-TE2A-AR-06, RC-3095 | Gastrin-releasing peptide receptors-GRPR | [149,173] | |
Ovary | PD176252 | Gastrin-releasing peptide receptors-GRPR, neuromedin B receptor-NMBR | [174] | |
Glioma | PD176252, PD168368 | Neuromedin B receptor-NMBR | [175] | |
Pancreatic | RC-3095, RC-3925-II, RC-3940-II and RC-3950-II | Gastrin-releasing peptide receptors-GRPR | [173,176] | |
Neurotensin | Breast | 99mTc-NT-XIX, 188Re-NT-XIX, 18F-DEG-VS-NT | Neurotensin receptor-NTSR | [145,146] |
Pancreatic adenocarcinoma | 177 Lu-3BP-227 | Neurotensin receptor-1 NTSR-1 | [177] | |
CRC | Sodium butyrate, SR48692, Curcumin, Cyanidin, SR 48692, 177 Lu-3BP-227 | Neurotensin receptor-NTSR | [109,124] | |
Small cell lung carcinoma | SR48692 | Neurotensin receptor-1 NTSR-1 | [178] | |
Vasoactive intestinal peptide-VIP | CRC | NTS6-11VIP7-28 | Vasoactive intestinal peptide receptor-VPAC1/2 | [128] |
Breast | VIP hybrid | Vasoactive intestinal peptide receptor VIP receptor | [179] | |
Substance P | Breast | Aprepitant, L-732,138, L-733,060, CP-96345, C-9994, MEN 11467, SR14033, Spantide III | Neurokinin 1 receptor-NK1R | [91,142,143,144] |
CRC | Spantide 1, Aprepitant, Fosaprepitant, GR 159897 | Neurokinin 1 receptor-NK1R | [90,129,130] | |
Neuropeptide Y | Breast | BIBP3226 | Y1R | [131] |
BIIE0246 | Y2R | |||
L-152,804 | Y5R | |||
Colon adenocarcinoma | - | Y2R | [132] | |
Prostate | BIBP32226 | Y1R | [150] | |
Orexin | Gastrointestinal tumors and CRC | NSC-87877, PD169316 | Orexin receptor -OX1R | [136,137] |
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Srivastava, A.; Rikhari, D.; Pradhan, B.; Bharadwaj, K.K.; Gaballo, A.; Quarta, A.; Jena, M.; Srivastava, S.; Ragusa, A. An Insight into Neuropeptides Inhibitors in the Biology of Colorectal Cancer: Opportunity and Translational Perspectives. Appl. Sci. 2022, 12, 8990. https://doi.org/10.3390/app12188990
Srivastava A, Rikhari D, Pradhan B, Bharadwaj KK, Gaballo A, Quarta A, Jena M, Srivastava S, Ragusa A. An Insight into Neuropeptides Inhibitors in the Biology of Colorectal Cancer: Opportunity and Translational Perspectives. Applied Sciences. 2022; 12(18):8990. https://doi.org/10.3390/app12188990
Chicago/Turabian StyleSrivastava, Ankit, Deeksha Rikhari, Biswajita Pradhan, Kaushik Kumar Bharadwaj, Antonio Gaballo, Alessandra Quarta, Mrutyunjay Jena, Sameer Srivastava, and Andrea Ragusa. 2022. "An Insight into Neuropeptides Inhibitors in the Biology of Colorectal Cancer: Opportunity and Translational Perspectives" Applied Sciences 12, no. 18: 8990. https://doi.org/10.3390/app12188990