Nicotinic acetylcholine receptor as a pharmacological target in lung cancer
DOI:
https://doi.org/10.14720/abs.65.1.15941Keywords:
nAChR, antagonist, apoptosis, lung cancer, nanodelivery system, nicotineAbstract
Lung cancer is a widespread form of cancer with a low survival rate. Tobacco smoking is a major risk factor for the development of lung cancer, as tobacco smoke contains many carcinogens. Nicotine, which is not classified as a carcinogen, is the main component of tobacco, responsible for addiction and recent research suggests that nicotine, independent of other tobacco components, may contribute to the development and progression of cancer. Nicotine, as an agonist of nicotinic acetylcholine receptors (nAChRs), promotes cell proliferation, prevents apoptosis, and has an important role in promoting angiogenesis and metastasis of cancer cells. The realisation that nAChRs are involved in the development and progression of lung cancer has raised the idea of using nAChR antagonists that would counteract the adverse effects of nicotine. Currently, there are only a few nAChR antagonists for which anticancer efficacy has been investigated. Many of the known antagonists do not act selectively on nAChR subtypes that are overexpressed in lung cancer cells. Nonselective nAChR antagonists can cause adverse side effects by acting on nAChR subtypes expressed on non-cancerous cells. In order to avoid such side effects, it is necessary to ensure that a given antagonist acts predominantly on cancer cells. This can be achieved by using nano delivery systems that are preferentially uptaken by cancer cells. In this article, we present the latest achievements in the development of drugs for the treatment of lung cancer based on nAChR antagonists delivered to the site of action by nanoparticles.
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Anderson, C.F., Grimmett, M.E., Domalewski, C.J., Cui, H., 2020. Inhalable nanotherapeutics to improve treatment efficacy for common lung diseases. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, 12 (1), e1586. DOI: https://doi.org/10.1002/wnan.1586
Anselmo, A.C., Mitragotri, S., 2019. Nanoparticles in the clinic: An update. Bioengineering & Tran- slational Medicine, 4 (3), e10143. DOI: https://doi.org/10.1002/btm2.10143
Berne, S., Čemažar, M., Frangež, R., Juntes, P., Kranjc, S., Grandič, M., Savarin, M., Turk, T., 2018. APS8 Delays Tumor Growth in Mice by Inducing Apoptosis of Lung Adenocarcinoma Cells Ex- pressing High Number of α7 Nicotinic Receptors. Marine Drugs, 16 (10), 367. DOI: https://doi.org/10.3390/md16100367
Blanco, E., Shen, H., Ferrari, M., 2015. Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nature Biotechnology, 33 (9), 941. DOI: https://doi.org/10.1038/nbt.3330
Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R.L., Torre, L.A., Jemal, A., 2018. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countri- es. CA: A Cancer Journal for Clinicians, 68 (6), 394–424. DOI: https://doi.org/10.3322/caac.21492
Calles, A., Aguado, G., Sandoval, C., Álvarez, R., 2019. The role of immunotherapy in small cell lung cancer. Clinical and Translational Oncology, 21 (8), 961–976. DOI: https://doi.org/10.1007/s12094-018-02011-9
Carr, L.L., Jacobson, S., Lynch, D.A., Foreman, M.G., Flenaugh, E.L., Hersh, C.P., Sciurba, F.C., Wilson, D.O., Sieren, J.C., Mulhall, P., Kim, V., 2018. Features of COPD as predictors of lung cancer. Chest, 153 (6), 1326–1335. DOI: https://doi.org/10.1016/j.chest.2018.01.049
Cattaneo, M.G., Codignola, A., Vicentini, L.M., Clementi, F., Sher, E., 1993. Nicotine stimulates a sero- tonergic autocrine loop in human small-cell lung carcinoma. Cancer Research, 53 (22), 5566–5568.
Chen, J., Cheuk, I.W., Shin, V.Y., Kwong, A., 2019. Acetylcholine receptors: key players in cancer development. Surgical Oncology, 31, 46–53. DOI: https://doi.org/10.1016/j.suronc.2019.09.003
Chernyavsky, A.I., Shchepotin, I.B., Galitovkiy, V., Grando, S.A., 2015. Mechanisms of tumor-promoting activities of nicotine in lung cancer: synergistic effects of cell membrane and mitochondrial nicotinic acetylcholine receptors. BMC Cancer, 15 (1), 152. DOI: https://doi.org/10.1186/s12885-015-1158-4
Cho, K., Wang, X.U., Nie, S., Shin, D.M., 2008. Therapeutic nanoparticles for drug delivery in cancer. Clinical Cancer Research, 14 (5), 1310–1316. DOI: https://doi.org/10.1158/1078-0432.CCR-07-1441
Dasgupta, P., Kinkade, R., Joshi, B., DeCook, C., Haura, E., Chellappan, S., 2006. Nicotine inhibits apoptosis induced by chemotherapeutic drugs by up-regulating XIAP and survivin. Proceedings of the National Academy of Sciences, 103 (16), 6332–6337. DOI: https://doi.org/10.1073/pnas.0509313103
Doroshow, D.B., Sanmamed, M.F., Hastings, K., Politi, K., Rimm, D.L., Chen, L., Ignacio, M., Kurt, A.S., Herbst, R.S., 2019. Immunotherapy in non–small cell lung cancer: facts and hopes. Clinical Cancer Research, 25 (15), 4592–4602. DOI: https://doi.org/10.1158/1078-0432.CCR-18-1538
Doroudian, M., Azhdari, M.H., Goodarzi, N., O’Sullivan, D., Donnelly, S.C., 2021. Smart Nanotherapeutics and Lung Cancer. Pharmaceutics, 13 (11), 1972. DOI: https://doi.org/10.3390/pharmaceutics13111972
El-Bayoumy, K., Stoner, G., 2022. Use of Freeze-dried Watercress for Detoxification of Carcinogens and Toxicants in Smokers: Implications of the Findings and Potential Opportunities. Cancer Prevention Research, 15 (3), 139–141. DOI: https://doi.org/10.1158/1940-6207.CAPR-21-0633
Ferchmin, P.A., Pagán, O.R., Ulrich, H., Szeto, A.C., Hann, R.M., Eterović, V.A., 2009. Actions of oc-15 tocoral and tobacco cembranoids on nicotinic receptors. Toxicon: official journal of the International Society on Toxinology, 54 (8), 1174–1182. DOI: https://doi.org/10.1016/j.toxicon.2009.02.033
Friedman, J.R., Richbart, S.D., Merritt, J.C., Brown, K.C., Nolan, N.A., Akers, A.T., Lau, J.K., Robateau, Z.R., Miles, S.L., Dasgupta, P., 2019. Acetylcholine signaling system in progression of lung cancers. Pharmacology and Therapeutics, 194, 222–254. DOI: https://doi.org/10.1016/j.pharmthera.2018.10.002
Grando, S.A., 2014. Connections of nicotine to cancer. Nature Reviews Cancer, 14 (6), 419–429. DOI: https://doi.org/10.1038/nrc3725
Grozio, A., Paleari, L., Catassi, A., Servent, D., Cilli, M., Piccardi, F., Paganuzzi, M., Cesario, A., Granone, P., Mourier, G., Russo, P., 2008. Natural agents targeting the α7‐nicotinic‐receptor in NSCLC: A promising prospective in anti‐cancer drug development. International Journal of Can- DOI: https://doi.org/10.1002/ijc.23298
cer, 122 (8), 1911–1915.
Haywood, A.J., Steidinger, K.A., Truby, E.W., Bergquist, P.R., Bergquist, P.L., Adamson, J., Mackenzie, L., 2004. Comparative morphology and molecular phylogenetic analysis of three new species of the genus karenia (dinophyceae) from New Zealand. Journal of Phycology, 40, 165–179. DOI: https://doi.org/10.1111/j.0022-3646.2004.02-149.x
Houssen, W.E., Lu, Z., Edrada-Ebel, R., Chatzi, C., Tucker, S.J., Sepčić, K., Turk, T., Zovko, A., Shen, S., Mancini, I., Scott, R.H., 2010. Chemical synthesis and biological activities of 3-alkyl pyridinium polymeric analogues of marine toxins. Journal of Chemical Biology, 3 (3), 113–125. DOI: https://doi.org/10.1007/s12154-010-0036-4
Hu, T., Burton, I.W., Cembella, A.D., Curtis, J.M., Quilliam, M.A., Walter, J.A., Wright, J.L., 2001. Characterization of spirolides a, c, and 13-desmethyl c, new marine toxins isolated from toxic plankton and contaminated shellfish. Journal of Natural Products, 64 (3), 308–312. DOI: https://doi.org/10.1021/np000416q
Hurst, R., Rollema, H., Bertrand, D., 2013. Nicotinic acetylcholine receptors: from basic science to therapeutics. Pharmacology & Therapeutics, 137 (1), 22–54. DOI: https://doi.org/10.1016/j.pharmthera.2012.08.012
Imani, R., Dillert, R., Bahnemann, D.W., Pazoki, M., Apih, T., Kononenko, V., Repar, N., Kralj‐Iglič, V., Boschloo, G., Drobne, D., Edvinsson, T., 2017. Multifunctional Gadolinium‐Doped Mesoporous TiO2 Nanobeads: Photoluminescence, Enhanced Spin Relaxation, and Reactive Oxygen Species Photogeneration, Beneficial for Cancer Diagnosis and Treatment. Small, 13 (20), 1700349. DOI: https://doi.org/10.1002/smll.201700349
Jennings, K.R., Brown, D.G., Wright, D.P., 1986. Methyllycaconitine, a naturally occurring insecticide with a high affinity for the insect cholinergic receptor. Experientia, 42, 611–613. DOI: https://doi.org/10.1007/BF01955557
Jull, B., Plummer III, H.K., Schuller, H., 2001. Nicotinic receptor-mediated activation by the tobacco- specific nitrosamine NNK of a Raf-1/MAP kinase pathway, resulting in phosphorylation of c-myc in human small cell lung carcinoma cells and pulmonary neuroendocrine cells. Journal of Cancer Research and Clinical Oncology, 127 (12), 707–717. DOI: https://doi.org/10.1007/s004320100289
Kawai, H., Berg, D.K., 2001. Nicotinic acetylcholine receptors containing the α7 subunits on rat cor- tical neurons do not undergo long lasting inactivation even when upregulated by chronic nicotine exposure. Journal of Neurochemistry, 78 (6), 1367–1378. DOI: https://doi.org/10.1046/j.1471-4159.2001.00526.x
Kononenko, V., Narat, M., Drobne, D., 2015. Nanoparticle interaction with the immune system. Arhiv za Higijenu Rada i Toksikologiju, 66 (2), 97–108. DOI: https://doi.org/10.1515/aiht-2015-66-2582
Kononenko, V., Erman, A., Petan, T., Križaj, I., Kralj, S., Makovec, D., Drobne, D., 2017a. Harmful at non-cytotoxic concentrations: SiO2-SPIONs affect surfactant metabolism and lamellar body bioge- nesis in A549 human alveolar epithelial cells. Nanotoxicology, 11 (3), 419–429. DOI: https://doi.org/10.1080/17435390.2017.1309704
Kononenko, V., Imani, R., Repar, N., Benčina, M., Lorenzetti, M., Erman, A., Drobne, D., Iglič, A., 2017b. Phototoxicity of Mesoporous TiO2+ Gd Microbeads With Theranostic Potential. In: Advances in Biomembranes and Lipid Self-Assembly, Academic Press, 26, 153–171. DOI: https://doi.org/10.1016/bs.abl.2017.06.002
Koss, D.J., Hindley, K.P., David, K.C., Mancini, I., Guella, G., Sepčić, K., Turk, T., Rebolj, K., Riedel, G., Platt, B., Scott, R.H., 2007. A comparative study of the actions of alkylpyridinium salts from a marine sponge and related synthetic compounds in rat cultured hippocampal neurones. BMC Pharmacology, 7 (1), 1. DOI: https://doi.org/10.1186/1471-2210-7-1
Liu, Q., Yu, K.W., Chang, Y.C., Lukas, R.J., Wu, J., 2008. Agonist-induced hump current production in heterologously-expressed human alpha4beta2-nicotinic acetylcholine receptors. Acta Pharma- cologica Sinica, 29 (3), 305–319. DOI: https://doi.org/10.1111/j.1745-7254.2008.00760.x
Kononenko et al.: Nikotinski acetilholinski receptor in pljučni rak
Lucky, S.S., Soo, K.C., Zhang, Y., 2015. Nanoparticles in photodynamic therapy. Chemical Reviews, 115 (4), 1990-2042. DOI: https://doi.org/10.1021/cr5004198
Maneckjee, R., Minna, J.D., 1990. Opioid and nicotine receptors affect growth regulation of human lung cancer cell lines. Proceedings of the National Academy of Sciences, 87 (9), 3294–3298. DOI: https://doi.org/10.1073/pnas.87.9.3294
Mao, Y., Yang, D., He, J., Krasna, M.J., 2016. Epidemiology of lung cancer. Surgical Oncology Clinics, 25 (3), 439–445. DOI: https://doi.org/10.1016/j.soc.2016.02.001
Marques, P., Piqueras, L., Sanz, M.J., 2021. An updated overview of e-cigarette impact on human health. Respiratory Research, 22, 1–14. DOI: https://doi.org/10.1186/s12931-021-01737-5
Mucchietto, V., Crespi, A., Fasoli, F., Clementi, F., Gotti, C., 2016. Neuronal acetylcholine nicotinic receptors as new targets for lung cancer treatment. Current Pharmaceutical Design, 22 (14), 2160–2169. DOI: https://doi.org/10.2174/1381612822666160203144114
Mucchietto, V., Fasoli, F., Pucci, S., Moretti, M., Benfante, R., Maroli, A., Di Lascio, S., Bolchi, C., Pallavicini, M., Dowell, C., McIntosh, M., 2018. α9‐and α7‐containing receptors mediate the pro‐proliferative effects of nicotine in the A549 adenocarcinoma cell line. British Journal of Phar- DOI: https://doi.org/10.1111/bph.13954
macology, 175 (11), 1957–1972. DOI: https://doi.org/10.2307/1086090
Murthy, S.K., 2007. Nanoparticles in modern medicine: state of the art and future challenges. International Journal of Nanomedicine, 2 (2), 129.
Onkološki inštitut Ljubljana, Rak pljuč, https://www.onko-i.si/za-javnost-in-bolnike/vrste-raka/rak-pljuc (4. 4. 2022)
Paleari, L., Negri, E., Catassi, A., Cilli, M., Servent, D., D‘Angelillo, R., Cesario, A., Russo, P., Fini, M., 2009a. Inhibition of nonneuronal α7-nicotinic receptor for lung cancer treatment. American Journal of Respiratory and Critical Care Medicine, 179 (12), 1141–1150. DOI: https://doi.org/10.1164/rccm.200806-908OC
Paleari, L., Cesario, A., Fini, M., Russo, P., 2009b. Foundation review: α7-nicotinic receptor anta- gonists at the beginning of a clinical era for NSCLC and mesothelioma? Drug Discovery Today, 14, 822–836. DOI: https://doi.org/10.1016/j.drudis.2009.06.016
Paranjpe, M., Müller-Goymann, C., 2014. Nanoparticle-mediated pulmonary drug delivery: a review. International Journal of Molecular Sciences, 15 (4), 5852–5873. DOI: https://doi.org/10.3390/ijms15045852
Picciotto, M.R., Kenny, P.J., 2021. Mechanisms of nicotine addiction. Cold Spring Harbor Perspectives in Medicine, 11 (5), a039610. DOI: https://doi.org/10.1101/cshperspect.a039610
Ren, J., Zhu, X., Xu, P., Li, R., Fu, Y., Dong, S., Zhangsun, D., Wu, Y., Luo, S., 2019. d-Amino Acid Substitution of α-Conotoxin RgIA Identifies its Critical Residues and Improves the Enzymatic Stability. Marine Drugs, 17 (3), 142. DOI: https://doi.org/10.3390/md17030142
Riley, R.S., June, C.H., Langer, R., Mitchell, M.J., 2019. Delivery technologies for cancer immuno-therapy. Nature reviews Drug Discovery, 18 (3), 175–196. DOI: https://doi.org/10.1038/s41573-018-0006-z
Sadhukha, T., Wiedmann, T.S., Panyam, J., 2013. Inhalable magnetic nanoparticles for targeted hyper-thermia in lung cancer therapy. Biomaterials, 34 (21), 5163–5171. DOI: https://doi.org/10.1016/j.biomaterials.2013.03.061
Samson, A.O., Levitt, M., 2008. Inhibition mechanism of the acetylcholine receptor by alpha-neurotoxins as revealed by normal-mode dynamics“. Biochemistry, 47 (13), 4065–70. DOI: https://doi.org/10.1021/bi702272j
Sanner, T., Grimsrud, T.K., 2015. Nicotine: carcinogenicity and effects on response to cancer treatment–a review. Frontiers in Oncology, 5, 196. DOI: https://doi.org/10.3389/fonc.2015.00196
Schuller, H.M., 1989. Cell type specific, receptor-mediated modulation of growth kinetics in human lung cancer cell lines by nicotine and tobacco-related nitrosamines. Biochemical Pharmacology, 38 (20), 3439–3442. DOI: https://doi.org/10.1016/0006-2952(89)90112-3
Schuller, H.M., 2007. Nitrosamines as nicotinic receptor ligands. Life sciences, 80 (24-25), 2274–2280. Schuller, H.M., Al-Wadei, H.A., Majidi, M., 2008. Gamma aminobutyric acid, a potential tumor suppressor for small airway-derived lung adenocarcinoma. Carcinogenesis, 29 (10), 1979–1985. Schuller, H.M., 2009. Is cancer triggered by altered signalling of nicotinic acetylcholine receptors?. Nature Reviews Cancer, 9 (3), 195. DOI: https://doi.org/10.1093/carcin/bgn041
Schuller, H.M., 2019. The impact of smoking and the influence of other factors on lung cancer. Expert Review of Respiratory Medicine, 13 (8), 761–769. DOI: https://doi.org/10.1080/17476348.2019.1645010
Sepčić, K., Guella, G., Mancini, I., Pietra, F., Serra, M.D., Menestrina, G., Tubbs, K., Maček, P., Turk, T. (1997). Characterization of anticholinesterase-active 3-alkyl pyridinium polymers from the marine sponge Reniera sarai in aqueous solutions. Journal of Natural Products, 60 (10), 991–996 DOI: https://doi.org/10.1021/np970292q
Shen, A.M., Minko, T., 2020. Pharmacokinetics of inhaled nanotherapeutics for pulmonary delivery. Journal of Controlled Release, 326, 222–244. DOI: https://doi.org/10.1016/j.jconrel.2020.07.011
Shiraishi, K., Kunitoh, H., Daigo, Y., Takahashi, A., Goto, K., Sakamoto, H., Ohnami, S., Shimada, Y., Ashikawa, K., Saito, A., Watanabe, S.I., 2012. A genome-wide association study identifies two new susceptibility loci for lung adenocarcinoma in the Japanese population. Nature Genetics, 44 (8), 900. DOI: https://doi.org/10.1038/ng.2353
Siemann, D.W., 2011. The unique characteristics of tumor vasculature and preclinical evidence for its selective disruption by tumor-vascular disrupting agents. Cancer Treatment Reviews, 37 (1), 63–74. Skok, M., Gergalova, G., Lykhmus, O., Kalashnyk, O., Koval, L., Uspenska, K., 2016. Nicotinic acetylcholine receptors in mitochondria: subunit composition, function and signaling. Neurotransmitter, 3, e1290 DOI: https://doi.org/10.1016/j.ctrv.2010.05.001
Thandra, K.C., Barsouk, A., Saginala, K., Aluru, J.S., Barsouk, A., 2021. Epidemiology of lung cancer. Contemporary Oncology, 25 (1), 45. DOI: https://doi.org/10.5114/wo.2021.103829
Turk, T., Frangež, R., Sepčić, K., 2007. Mechanisms of toxicity of 3-alkyl pyridinium polymers from marine sponge Reniera sarai. Marine Drugs, 5, 157–167. DOI: https://doi.org/10.3390/MD504157
Turk, T., Sepčić, K., Mancini, I., Guella, G., 2008. 3-Akylpyridinium and 3-alkylpyridine compounds from marine sponges, their synthesis, biological activities and potential use. In: Studies in Natural Products Chemistry, Elsevier, 35, 355–397. DOI: https://doi.org/10.1016/S1572-5995(08)80009-9
Utkin, Y.N., 2013. Three-finger toxins, a deadly weapon of elapid venom–milestones of discovery. Toxicon, 62, 50–55. DOI: https://doi.org/10.1016/j.toxicon.2012.09.007
Vulfius, C.A., Kasheverov, I.E., Starkov, V.G., Osipov, A.V., Andreeva, T.V., Filkin, S.Y., Gorbacheva, E.V., Astashev, M.E., Tsetlin, V.I., Utkin, Y.N., 2014. Inhibition of nicotinic acetylcholine receptors, a novel facet in the pleiotropic activities of snake venom phospholipases A2. PloS One, 9 (12), e115428. DOI: https://doi.org/10.1371/journal.pone.0115428
Wang, S., Hu, Y., 2018. α7 nicotinic acetylcholine receptors in lung cancer. Oncology Letters, 16 (2), 1375–1382. DOI: https://doi.org/10.3892/ol.2018.8841
Wessler, I., Kirkpatrick, C.J., 2008. Acetylcholine beyond neurons: the non-neuronal cholinergic system in humans. British Journal of Pharmacology, 154 (8), 1558–1571. DOI: https://doi.org/10.1038/bjp.2008.185
Whiteaker, P., Christensen, S., Yoshikami, D., Dowell, C., Watkins, M., Gulyas, J., Rivier, J., Olivera, B.M., McIntosh, J.M., 2007. Discovery, synthesis, and structure activity of a highly selective alpha7 nicotinic acetylcholine receptor antagonist. Biochemistry, 46 (22), 6628–6638. DOI: https://doi.org/10.1021/bi7004202
Wintersteiner, O., Dutcher, J.D., 1943. Curare alkaloids from Chondodendron tometosum. Science, 97, 467–470. DOI: https://doi.org/10.1126/science.97.2525.467
Wittenberg, R.E., Wolfman, S.L., De Biasi, M., Dani, J.A., 2020. Nicotinic acetylcholine receptors and nicotine addiction: A brief introduction. Neuropharmacology, 177, 108256. DOI: https://doi.org/10.1016/j.neuropharm.2020.108256
Wolfram, J., Ferrari, M., 2019. Clinical cancer nanomedicine. Nano Today, 25, 85–98. DOI: https://doi.org/10.1016/j.nantod.2019.02.005
Ye, D., Li, Y., Gu, N., 2018. Magnetic labeling of natural lipid encapsulations with iron-based nanoparticles. Nano Research, 11 (6), 2970–2991. DOI: https://doi.org/10.1007/s12274-018-1980-5
Zhu, X., Pan, S., Xu, M., Zhang, L., Yu, J., Yu, J., Wu, Y., Fan, Y., Li, H., Kasheverov, I.E., Kudryavtsev, D.S., Tsetlin, V.I., Xue, Y., Zhangsun, D., Wang, X., Luo, S., 2020. High Selectivity of an α-Conotoxin LvIA Analogue for α3β2 Nicotinic Acetylcholine Receptors Is Mediated by β2 Functionally Important Residues. Journal of Medicinal Chemistry, 63 (22), 13656–13668. DOI: https://doi.org/10.1021/acs.jmedchem.0c00975
Zovko, A., Viktorsson, K., Lewensohn, R., Kološa, K., Filipič, M., Xing, H., Kem, W.R., Paleari, L., Turk, T., 2013. APS8, a polymeric alkylpyridinium salt blocks α7 nAChR and induces apoptosis in non-small cell lung carcinoma. Marine Drugs, 11 (7), 2574–2594. DOI: https://doi.org/10.3390/md11072574
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