Ion Channels in Multiple Myeloma: Pathogenic Role and Therapeutic Perspectives
Abstract
:1. Introduction
2. Ion Channels in MM
2.1. Potassium Channels
2.2. Chloride Channels
2.3. Calcium Channels and Transporters
2.4. Non-Selective Cation Channels
2.5. Proton Channels
2.6. Organelle-Related Ion Channels
3. Ion Channels and Drug Resistance
4. Ion Channels Inhibition as Anti-Myeloma Therapy
Channels | Ion Channels Modulator | Molecular Effects | Biological Effects | Combination Strategy | Ref. |
---|---|---|---|---|---|
TRPV2 | Cannabidiol | Activation of ERK, AKT and NF-κB | Inhibits cell growth and cell cycle progression, induces cell death and mitochondrial- and ROS-dependent necrosis | Bortezomib | [92] |
SOCs | MTI-101 | - | Improves cell and mice survival | Bortezomib | [88] |
Ca2+ channels | Tipirfanib | - | Overcomes fibronectin- and stroma-mediated drug resistance | Bortezomib | [93] |
TRPA1 | HC030031 | Activation of p38-MAPK and JNK | Alleviates bortezomib-induced neuropathic pain | Bortezomib | [95,96] |
Cav3.2 T-type calcium channels | (2R/S)-6-prenylnaringenin, KTt-45 and TTA-A2 | - | Alleviates bortezomib-induced neuropathic pain | Bortezomib | [97] |
TRPM8 | Menthol (agonist) | - | Alleviates bortezomib-induced neuropathic pain | Bortezomib | [98] |
TRPV1 | Capsaicin (agonist) | - | Mediates thalidomide-induced analgesia and cognitive dysfunction | Thalidomide | [99] |
AMG9810 | Inhibition of ubiquitin pathway | Mitochondrial ROS accumulation, mitophagy and MM cells death | Bortezomib | [63] | |
Calcium-activated K+ (BK) channels | Paxilline | Reduces K+ conductance | Alleviates thalidomide-induced cognitive dysfunction | Thalidomide | [100] |
5. Concluding Remarks and Future Perspectives
Author Contributions
Funding
Conflicts of Interest
References
- Kumar, S.K.; Rajkumar, V.; Kyle, R.A.; van Duin, M.; Sonneveld, P.; Mateos, M.V.; Gay, F.; Anderson, K.C. Multiple myeloma. Nat. Rev. Dis. Prim. 2017, 3, 17046. [Google Scholar] [CrossRef]
- Mateos, M.V.; Landgren, O. MGUS and Smoldering Multiple Myeloma: Diagnosis and Epidemiology. Cancer Treat. Res. 2016, 169, 3–12. [Google Scholar] [CrossRef]
- Manier, S.; Sacco, A.; Leleu, X.; Ghobrial, I.M.; Roccaro, A.M. Bone marrow microenvironment in multiple myeloma progression. J. Biomed. Biotechnol. 2012, 2012, 157496. [Google Scholar] [CrossRef]
- Di Marzo, L.; Desantis, V.; Solimando, A.G.; Ruggieri, S.; Annese, T.; Nico, B.; Fumarulo, R.; Vacca, A.; Frassanito, M.A. Microenvironment drug resistance in multiple myeloma: Emerging new players. Oncotarget 2016, 7, 60698–60711. [Google Scholar] [CrossRef] [Green Version]
- Gadsby, D.C. Ion channels versus ion pumps: The principal difference, in principle. Nat. Rev. Mol. Cell Biol. 2009, 10, 344–352. [Google Scholar] [CrossRef] [Green Version]
- Rosendo-Pineda, M.J.; Moreno, C.M.; Vaca, L. Role of ion channels during cell division. Cell Calcium 2020, 91, 102258. [Google Scholar] [CrossRef]
- Prevarskaya, N.; Skryma, R.; Shuba, Y. Ion Channels in Cancer: Are Cancer Hallmarks Oncochannelopathies? Physiol. Rev. 2018, 98, 559–621. [Google Scholar] [CrossRef] [Green Version]
- Litan, A.; Langhans, S.A. Cancer as a channelopathy: Ion channels and pumps in tumor development and progression. Front. Cell. Neurosci. 2015, 9, 86. [Google Scholar] [CrossRef] [Green Version]
- Altamura, C.; Gavazzo, P.; Pusch, M.; Desaphy, J.F. Ion Channel Involvement in Tumor Drug Resistance. J. Pers. Med. 2022, 12, 210. [Google Scholar] [CrossRef]
- Sørensen, B.H.; Dam, C.S.; Stürup, S.; Lambert, I.H. Dual role of LRRC8A-containing transporters on cisplatin resistance in human ovarian cancer cells. J. Inorg. Biochem. 2016, 160, 287–295. [Google Scholar] [CrossRef]
- Gradogna, A.; Gaitán-Peñas, H.; Boccaccio, A.; Estévez, R.; Pusch, M. Cisplatin activates volume sensitive LRRC8 channel mediated currents in Xenopus oocytes. Channels 2017, 11, 254–260. [Google Scholar] [CrossRef] [Green Version]
- Biasiotta, A.; D’Arcangelo, D.; Passarelli, F.; Nicodemi, E.; Facchiano, A. Ion channels expression and function are strongly modified in solid tumors and vascular malformations. J. Transl. Med. 2016, 14, 285. [Google Scholar] [CrossRef] [Green Version]
- Djamgoz, M.B.A.; Fraser, S.P.; Brackenbury, W.J. In vivo evidence for voltage-gated sodium channel expression in carcinomas and potentiation of metastasis. Cancers 2019, 11, 1675. [Google Scholar] [CrossRef] [Green Version]
- Altamura, C.; Greco, M.R.; Carratù, M.R.; Cardone, R.A.; Desaphy, J.F. Emerging Roles for Ion Channels in Ovarian Cancer: Pathomechanisms and Pharmacological Treatment. Cancers 2021, 13, 668. [Google Scholar] [CrossRef] [PubMed]
- Hofschröer, V.; Najder, K.; Rugi, M.; Bouazzi, R.; Cozzolino, M.; Arcangeli, A.; Panyi, G.; Schwab, A. Ion channels orchestrate pancreatic ductal adenocarcinoma progression and therapy. Front. Pharmacol. 2021, 11, 586599. [Google Scholar] [CrossRef] [PubMed]
- Davenport, B.; Li, Y.; Heizer, J.W.; Schmitz, C.; Perraud, A.L. Signature Channels of Excitability no More: L-Type Channels in Immune Cells. Front. Immunol. 2015, 6, 375. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Miller, C. An overview of the potassium channel family. Genome Biol. 2000, 1, reviews0004.1. [Google Scholar] [CrossRef] [PubMed]
- Hibino, H.; Inanobe, A.; Furutani, K.; Murakami, S.; Findlay, I.; Kurachi, Y. Inwardly rectifying potassium channels: Their structure, function, and physiological roles. Physiol. Rev. 2010, 90, 291–366. [Google Scholar] [CrossRef] [Green Version]
- González, C.; Baez-Nieto, D.; Valencia, I.; Oyarzún, I.; Rojas, P.; Naranjo, D.; Latorre, R. K(+) channels: Function-structural overview. Compr. Physiol. 2012, 2, 2087–2149. [Google Scholar] [CrossRef]
- Comes, N.; Serrano-Albarrás, A.; Capera, J.; Serrano-Novillo, C.; Condom, E.; Ramón, Y.; Cajal, S.; Ferreres, J.C.; Felipe, A. Involvement of potassium channels in the progression of cancer to a more malignant phenotype. Biochim. Biophys. Acta 2015, 1848, 2477–2492. [Google Scholar] [CrossRef] [Green Version]
- Felipe, A.; Bielanska, J.; Comes, N.; Vallejo, A.; Roig, S.; Ramón, Y.; Cajal, S.; Condom, E.; Hernández-Losa, J.; Ferreres, J.C. Targeting the voltage-dependent K(+) channels Kv1.3 and Kv1.5 as tumor biomarkers for cancer detection and prevention. Curr. Med. Chem. 2012, 19, 661–674. [Google Scholar] [CrossRef]
- D’Amico, M.; Gasparoli, L.; Arcangeli, A. Potassium channels: Novel emerging biomarkers and targets for therapy in cancer. Recent Pat. Anticancer Drug Discov. 2013, 8, 53–65. [Google Scholar] [CrossRef]
- Wang, W.; Fan, Y.; Wang, S.; Wang, L.; He, W.; Zhang, Q.; Li, X. Effects of voltage-gated K+ channel on cell proliferation in multiple myeloma. Sci. World J. 2014, 2014, 785140. [Google Scholar] [CrossRef] [Green Version]
- Zhou, J.; Wang, W.; Wei, Q.F.; Feng, T.M.; Tan, L.J.; Yang, B.F. Effects of arsenic trioxide on voltage-dependent potassium channels and on cell proliferation of human multiple myeloma cells. Chin. Med. J. 2007, 120, 1266–1269. [Google Scholar] [CrossRef]
- Wu, S.N.; Yu, H.S.; Jan, C.R.; Li, H.F.; Yu, C.L. Inhibitory effects of berberine on voltage- and calcium-activated potassium currents in human myeloma cells. Life Sci. 1998, 62, 2283–2294. [Google Scholar] [CrossRef]
- Nurul, H.M.; Tae-Hoon, C.; Grössinger, E.M.; Wulff, H.; Chandy, G.K.; Joo, C.W. The KCa2.3 potassium channel at 1q21 is associated with disease progression and reduced survival during relapse in multiple myeloma. Clin. Lymphoma Myeloma Leuk. 2015, 15, E226. [Google Scholar] [CrossRef]
- Birerdinc, A.; Nohelty, E.; Marakhonov, A.; Manyam, G.; Panov, I.; Coon, S.; Nikitin, E.; Skoblov, M.; Chandhoke, V.; Baranova, A. Pro-apoptotic and antiproliferative activity of human KCNRG, a putative tumor suppressor in 13q14 region. Tumour Biol. 2010, 31, 33–45. [Google Scholar] [CrossRef] [Green Version]
- Verkman, A.S.; Galietta, L.J. Chloride channels as drug targets. Nat. Rev. Drug Discov. 2009, 8, 153–171. [Google Scholar] [CrossRef] [Green Version]
- Gururaja Rao, S.; Patel, N.J.; Singh, H. Intracellular Chloride Channels: Novel Biomarkers in Diseases. Front. Physiol. 2020, 11, 96. [Google Scholar] [CrossRef] [Green Version]
- Jentsch, T.J.; Stein, V.; Weinreich, F.; Zdebik, A.A. Molecular structure and physiological function of chloride channels. Physiol. Rev. 2002, 82, 503–568. [Google Scholar] [CrossRef]
- Kim, H.J.; Lee, P.C.; Hong, J.H. Chloride Channels and Transporters: Roles beyond Classical Cellular Homeostatic pH or Ion Balance in Cancers. Cancers 2022, 14, 856. [Google Scholar] [CrossRef]
- Levitan, I.; Garber, S.S. Voltage-dependent inactivation of volume-regulated Cl− current in human T84 colonic and B-cell myeloma cell lines. Pflugers Arch. 1995, 431, 297–299. [Google Scholar] [CrossRef]
- Du, Y.; Tu, Y.S.; Tang, Y.B.; Huang, Y.Y.; Zhou, F.M.; Tian, T.; Li, X.Y. Requirement of ClC-3 in G0/G1 to S Phase Transition Induced by IGF-1 via ERK1/2-Cyclins Cascade in Multiple Myeloma Cells. Clin. Lab. 2018, 64, 929–936. [Google Scholar] [CrossRef]
- Zhang, H.; Pang, Y.; Ma, C.; Li, J.; Wang, H.; Shao, Z. ClC5 Decreases the Sensitivity of Multiple Myeloma Cells to Bortezomib via Promoting Prosurvival Autophagy. Oncol. Res. 2018, 26, 421–429. [Google Scholar] [CrossRef]
- Frassanito, M.A.; De Veirman, K.; Desantis, V.; Di Marzo, L.; Vergara, D.; Ruggieri, S.; Annese, T.; Nico, B.; Menu, E.; Catacchio, I.; et al. Halting pro-survival autophagy by TGFβ inhibition in bone marrow fibroblasts overcomes bortezomib resistance in multiple myeloma patients. Leukemia 2016, 30, 640–648. [Google Scholar] [CrossRef]
- Di Lernia, G.; Leone, P.; Solimando, A.G.; Buonavoglia, A.; Saltarella, I.; Ria, R.; Ditonno, P.; Silvestris, N.; Crudele, L.; Vacca, A.; et al. Bortezomib Treatment Modulates Autophagy in Multiple Myeloma. J. Clin. Med. 2020, 9, 552. [Google Scholar] [CrossRef] [Green Version]
- Perez-Reyes, E.; Schneider, T. Calcium channels: Structure, function, and classification. Drug Dev. Res. 1994, 33, 295–318. [Google Scholar] [CrossRef]
- Alexander, S.P.; Christopoulos, A.; Davenport, A.P.; Kelly, E.; Mathie, A.; Peters, J.A.; Veale, E.L.; Armstrong, J.F.; Faccenda, E.; Harding, S.D.; et al. The concise guide to pharmacology 2021/22: G protein-coupled receptors. Br. J. Pharmacol. 2021, 178, S27–S156. [Google Scholar] [CrossRef]
- Thakker, R.V. Calcium-sensing receptor: Role in health and disease. Indian J. Endocrinol. Metab. 2012, 16, S213–S216. [Google Scholar] [CrossRef]
- Tennakoon, S.; Aggarwal, A.; Kállay, E. The calcium-sensing receptor and the hallmarks of cancer. Biochim. Biophys. Acta 2016, 1863, 1398–1407. [Google Scholar] [CrossRef] [Green Version]
- Marchi, S.; Pinton, P. Alterations of calcium homeostasis in cancer cells. Curr. Opin. Pharmacol. 2016, 29, 1–6. [Google Scholar] [CrossRef] [PubMed]
- Stewart, T.A.; Yapa, K.T.; Monteith, G.R. Altered calcium signaling in cancer cells. Biochim. Biophys. Acta 2015, 1848, 2502–2511. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zagouri, F.; Kastritis, E.; Zomas, A.; Terpos, E.; Katodritou, E.; Symeonidis, A.; Delimpasi, S.; Pouli, A.; Vassilakopoulos, T.P.; Michalis, E.; et al. Hypercalcemia remains an adverse prognostic factor for newly diagnosed multiple myeloma patients in the era of novel antimyeloma therapies. Eur. J. Haematol. 2017, 99, 409–414. [Google Scholar] [CrossRef]
- Yamaguchi, T.; Yamauchi, M.; Sugimoto, T.; Chauhan, D.; Anderson, K.C.; Brown, E.M.; Chihara, K. The extracellular calcium Ca2+o-sensing receptor is expressed in myeloma cells and modulates cell proliferation. Biochem. Biophys. Res. Commun. 2002, 299, 532–538. [Google Scholar] [CrossRef]
- Moreno, C.; Vaca, L. SOC and now also SIC: Store-operated and store-inhibited channels. IUBMB Life 2011, 63, 856–863. [Google Scholar] [CrossRef]
- Liou, J.; Kim, M.L.; Heo, W.D.; Jones, J.T.; Myers, J.W.; Ferrell, J.E., Jr.; Meyer, T. STIM is a Ca2+ sensor essential for Ca2+-store-depletion-triggered Ca2+ influx. Curr. Biol. 2005, 15, 1235–1241. [Google Scholar] [CrossRef] [Green Version]
- Nguyen, N.T.; Han, W.; Cao, W.M.; Wang, Y.; Wen, S.; Huang, Y.; Li, M.; Du, L.; Zhou, Y. Store-Operated Calcium Entry Mediated by ORAI and STIM. Compr. Physiol. 2018, 8, 981–1002. [Google Scholar] [CrossRef]
- Wang, W.; Ren, Y.; Wang, L.; Zhao, W.; Dong, X.; Pan, J.; Gao, H.; Tian, Y. Orai1 and Stim1 Mediate the Majority of Store-Operated Calcium Entry in Multiple Myeloma and Have Strong Implications for Adverse Prognosis. Cell. Physiol. Biochem. 2018, 48, 2273–2285. [Google Scholar] [CrossRef]
- Elzamzamy, O.M.; Johnson, B.E.; Chen, W.C.; Hu, G.; Penner, R.; Hazlehurst, L.A. Transient Receptor Potential C 1/4/5 Is a Determinant of MTI-101 Induced Calcium Influx and Cell Death in Multiple Myeloma. Cells 2021, 10, 1490. [Google Scholar] [CrossRef]
- Yanamandra, N.; Buzzeo, R.W.; Gabriel, M.; Hazlehurst, L.A.; Mari, Y.; Beaupre, D.M.; Cuevas, J. Tipifarnib-induced apoptosis in acute myeloid leukemia and multiple myeloma cells depends on Ca2+ influx through plasma membrane Ca2+ channels. J. Pharmacol. Exp. Ther. 2011, 337, 636–643. [Google Scholar] [CrossRef] [Green Version]
- Cheng, K.T.; Ong, H.L.; Liu, X.; Ambudkar, I.S. Contribution of TRPC1 and Orai1 to Ca(2+) entry activated by store depletion. Adv. Exp. Med. Biol. 2011, 704, 435–449. [Google Scholar] [CrossRef] [Green Version]
- Vangsted, A.J.; Klausen, T.W.; Gimsing, P.; Abildgaard, N.; Andersen, N.F.; Gang, A.O.; Holmström, M.; Gregersen, H.; Vogel, U.; Schwarz, P.; et al. Genetic variants in the P2RX7 gene are associated with risk of multiple myeloma. Eur. J. Haematol. 2014, 93, 172–174. [Google Scholar] [CrossRef]
- Paneesha, S.; Starczynski, J.; Pepper, C.; Delgado, J.; Hooper, L.; Fegan, C.; Pratt, G. The P2X7 receptor gene polymorphism 1513 A→C has no effect on clinical prognostic markers and survival in multiple myeloma. Leuk. Lymphoma 2006, 47, 281–284. [Google Scholar] [CrossRef]
- Farrell, A.W.; Gadeock, S.; Pupovac, A.; Wang, B.; Jalilian, I.; Ranson, M.; Sluyter, R. P2X7 receptor activation induces cell death and CD23 shedding in human RPMI 8226 multiple myeloma cells. Biochim. Biophys. Acta 2010, 1800, 1173–1182. [Google Scholar] [CrossRef]
- Agrawal, A.; Kruse, L.S.; Vangsted, A.J.; Gartland, A.; Jørgensen, N.R. Human P2X7 Receptor Causes Cycle Arrest in RPMI-8226 Myeloma Cells to Alter the Interaction with Osteoblasts and Osteoclasts. Cells 2020, 9, 2341. [Google Scholar] [CrossRef]
- Jørgensen, N.R.; Syberg, S.; Ellegaard, M. The role of P2X receptors in bone biology. Curr. Med. Chem. 2015, 22, 902–914. [Google Scholar] [CrossRef]
- Overes, I.M.; de Rijke, B.; van Horssen-Zoetbrood, A.; Fredrix, H.; de Graaf, A.O.; Jansen, J.H.; van Krieken, J.H.; Raymakers, R.A.; van der Voort, R.; de Witte, T.M.; et al. Expression of P2X5 in lymphoid malignancies results in LRH-1-specific cytotoxic T-cell-mediated lysis. Br. J. Haematol. 2008, 141, 799–807. [Google Scholar] [CrossRef]
- Pedersen, S.F.; Owsianik, G.; Nilius, B. TRP channels: An overview. Cell Calcium 2005, 38, 233–252. [Google Scholar] [CrossRef]
- Morelli, M.B.; Liberati, S.; Amantini, C.; Nabiss, M.; Santoni, M.; Farfariello, V.; Santoni, G. Expression and function of the transient receptor potential ion channel family in the hematologic malignancies. Curr. Mol. Pharmacol. 2013, 6, 137–148. [Google Scholar] [CrossRef]
- Omari, S.A.; Geraghty, D.P.; Khalafallah, A.A.; Venkat, P.; Shegog, Y.M.; Ragg, S.J.; de Bock, C.E.; Adams, M.J. Optimized flow cytometric detection of transient receptor potential vanilloid-1 (TRPV1) in human hematological malignancies. Med. Oncol. 2022, 39, 81. [Google Scholar] [CrossRef]
- Bai, H.; Zhu, H.; Yan, Q.; Shen, X.; Lu, X.; Wang, J.; Li, J.; Chen, L. TRPV2-induced Ca2+-calcineurin-NFAT signaling regulates differentiation of osteoclast in multiple myeloma. Cell Commun. Signal. 2018, 16, 68. [Google Scholar] [CrossRef] [Green Version]
- Amachi, R.; Hiasa, M.; Teramachi, J.; Harada, T.; Oda, A.; Nakamura, S.; Hanson, D.; Watanabe, K.; Fujii, S.; Miki, H.; et al. A vicious cycle between acid sensing and survival signaling in myeloma cells: Acid-induced epigenetic alteration. Oncotarget 2016, 7, 70447–70461. [Google Scholar] [CrossRef] [Green Version]
- Beider, K.; Rosenberg, E.; Dimenshtein-Voevoda, V.; Sirovsky, Y.; Vladimirsky, J.; Magen, H.; Ostrovsky, O.; Shimoni, A.; Bromberg, Z.; Weiss, L.; et al. Blocking of Transient Receptor Potential Vanilloid 1 (TRPV1) promotes terminal mitophagy in multiple myeloma, disturbing calcium homeostasis and targeting ubiquitin pathway and bortezomib-induced unfolded protein response. J. Hematol. Oncol. 2020, 13, 158. [Google Scholar] [CrossRef]
- DeCoursey, T.E. Voltage-gated proton channels: Molecular biology, physiology, and pathophysiology of the H(V) family. Physiol. Rev. 2013, 93, 599–652. [Google Scholar] [CrossRef]
- Schilling, T.; Gratopp, A.; DeCoursey, T.E.; Eder, C. Voltage-activated proton currents in human lymphocytes. J. Physiol. 2002, 545, 93–105. [Google Scholar] [CrossRef]
- Spugnini, E.P.; Sonveaux, P.; Stock, C.; Perez-Sayans, M.; De Milito, A.; Avnet, S.; Garcìa, A.G.; Harguindey, S.; Fais, S. Proton channels and exchangers in cancer. Biochim. Biophys. Acta 2015, 1848, 2715–2726. [Google Scholar] [CrossRef] [Green Version]
- Bare, D.J.; Cherny, V.V.; DeCoursey, T.E.; Abukhdeir, A.M.; Morgan, D. Correction: Expression and function of voltage gated proton channels (Hv1) in MDA-MB-231 cells. PLoS ONE 2020, 15, e0235158. [Google Scholar] [CrossRef]
- Wang, Y.; Li, S.J.; Pan, J.; Che, Y.; Yin, J.; Zhao, Q. Specific expression of the human voltage-gated proton channel Hv1 in highly metastatic breast cancer cells, promotes tumor progression and metastasis. Biochem. Biophys. Res. Commun. 2011, 412, 353–359. [Google Scholar] [CrossRef]
- Hondares, E.; Brown, M.A.; Musset, B.; Morgan, D.; Cherny, V.V.; Taubert, C.; Bhamrah, M.K.; Coe, D.; Marelli-Berg, F.; Gribben, J.G.; et al. Enhanced activation of an amino-terminally truncated isoform of the voltage-gated proton channel HVCN1 enriched in malignant B cells. Proc. Natl. Acad. Sci. USA 2014, 111, 18078–18083. [Google Scholar] [CrossRef] [Green Version]
- El Arfani, C.; De Veirman, K.; Maes, K.; De Bruyne, E.; Menu, E. Metabolic Features of Multiple Myeloma. Int. J. Mol. Sci. 2018, 19, 1200. [Google Scholar] [CrossRef] [Green Version]
- Hiasa, M.; Okui, T.; Allette, Y.M.; Ripsch, M.S.; Sun-Wada, G.H.; Wakabayashi, H.; Roodman, G.D.; White, F.A.; Yoneda, T. Bone Pain Induced by Multiple Myeloma Is Reduced by Targeting V-ATPase and ASIC3. Cancer Res. 2017, 77, 1283–1295. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Avnet, S.; Di Pompo, G.; Lemma, S.; Baldini, N. Cause and effect of microenvironmental acidosis on bone metastases. Cancer Metastasis Rev. 2019, 38, 133–147. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Leanza, L.; Biasutto, L.; Managò, A.; Gulbins, E.; Zoratti, M.; Szabò, I. Intracellular ion channels and cancer. Front. Physiol. 2013, 4, 227. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shoshan-Barmatz, V.; De Pinto, V.; Zweckstetter, M.; Raviv, Z.; Keinan, N.; Arbel, N. VDAC, a multi-functional mitochondrial protein regulating cell life and death. Mol. Asp. Med. 2010, 31, 227–285. [Google Scholar] [CrossRef]
- Liu, S.; Ishikawa, H.; Tsuyama, N.; Li, F.J.; Abroun, S.; Otsuyama, K.I.; Zheng, X.; Ma, Z.; Maki, Y.; Iqbal, M.S.; et al. Increased susceptibility to apoptosis in CD45(+) myeloma cells accompanied by the increased expression of VDAC1. Oncogene 2006, 25, 419–429. [Google Scholar] [CrossRef] [Green Version]
- Zheng, Y.; Shi, Y.; Tian, C.; Jiang, C.; Jin, H.; Chen, J.; Almasan, A.; Tang, H.; Chen, Q. Essential role of the voltage-dependent anion channel (VDAC) in mitochondrial permeability transition pore opening and cytochrome c release induced by arsenic trioxide. Oncogene 2004, 23, 1239–1247. [Google Scholar] [CrossRef] [Green Version]
- Kadow, S.; Schumacher, F.; Kramer, M.; Hessler, G.; Scholtysik, R.; Oubari, S.; Johansson, P.; Hüttmann, A.; Reinhardt, H.C.; Kleuser, B.; et al. Mitochondrial Kv1.3 Channels as Target for Treatment of Multiple Myeloma. Cancers 2022, 14, 1955. [Google Scholar] [CrossRef]
- Song, I.S.; Kim, H.K.; Lee, S.R.; Jeong, S.H.; Kim, N.; Ko, K.S.; Rhee, B.D.; Han, J. Mitochondrial modulation decreases the bortezomib-resistance in multiple myeloma cells. Int. J. Cancer 2013, 133, 1357–1367. [Google Scholar] [CrossRef]
- Landowski, T.H.; Megli, C.J.; Nullmeyer, K.D.; Lynch, R.M.; Dorr, R.T. Mitochondrial-mediated disregulation of Ca2+ is a critical determinant of Velcade (PS-341/bortezomib) cytotoxicity in myeloma cell lines. Cancer Res. 2005, 65, 3828–3836. [Google Scholar] [CrossRef] [Green Version]
- Feno, S.; Rizzuto, R.; Raffaello, A.; Vecellio Reane, D. The molecular complexity of the Mitochondrial Calcium Uniporter. Cell Calcium 2021, 93, 102322. [Google Scholar] [CrossRef]
- Marchi, S.; Vitto, V.A.M.; Danese, A.; Wieckowski, M.R.; Giorgi, C.; Pinton, P. Mitochondrial calcium uniporter complex modulation in cancerogenesis. Cell Cycle 2019, 18, 1068–1083. [Google Scholar] [CrossRef]
- Robak, P.; Drozdz, I.; Szemraj, J.; Robak, T. Drug resistance in multiple myeloma. Cancer Treat. Rev. 2018, 70, 199–208. [Google Scholar] [CrossRef]
- Rajkumar, S.V.; Kumar, S. Multiple Myeloma: Diagnosis and Treatment. Mayo Clin. Proc. 2016, 91, 101–119. [Google Scholar] [CrossRef] [Green Version]
- Valverde, M.A.; Díaz, M.; Sepúlveda, F.V.; Gill, D.R.; Hyde, S.C.; Higgins, C.F. Volume-regulated chloride channels associated with the human multidrug-resistance P-glycoprotein. Nature 1992, 355, 830–883. [Google Scholar] [CrossRef]
- Wilczyński, B.; Dąbrowska, A.; Saczko, J.; Kulbacka, J. The Role of Chloride Channels in the Multidrug Resistance. Membranes 2021, 12, 38. [Google Scholar] [CrossRef]
- Planells-Cases, R.; Lutter, D.; Guyader, C.; Gerhards, N.M.; Ullrich, F.; Elger, D.A.; Kucukosmanoglu, A.; Xu, G.; Voss, F.K.; Reincke, S.M.; et al. Subunit composition of VRAC channels determines substrate specificity and cellular resistance to Pt-based anti-cancer drugs. EMBO J. 2015, 34, 2993–3008. [Google Scholar] [CrossRef]
- Santoni, G.; Amantini, C.; Maggi, F.; Marinelli, O.; Santoni, M.; Morelli, M.B. The Mucolipin TRPML2 Channel Enhances the Sensitivity of Multiple Myeloma Cell Lines to Ibrutinib and/or Bortezomib Treatment. Biomolecules 2022, 12, 107. [Google Scholar] [CrossRef]
- Emmons, M.F.; Anreddy, N.; Cuevas, J.; Steinberger, K.; Yang, S.; McLaughlin, M.; Silva, A.; Hazlehurst, L.A. MTI-101 treatment inducing activation of Stim1 and TRPC1 expression is a determinant of response in multiple myeloma. Sci. Rep. 2017, 7, 2685. [Google Scholar] [CrossRef]
- Shi, Q.; Chen, L. Cereblon: A Protein Crucial to the Multiple Functions of Immunomodulatory Drugs as well as Cell Metabolism and Disease Generation. J. Immunol. Res. 2017, 2017, 9130608. [Google Scholar] [CrossRef] [Green Version]
- Kim, H.K.; Ko, T.H.; Nyamaa, B.; Lee, S.R.; Kim, N.; Ko, K.S.; Rhee, B.D.; Park, C.S.; Nilius, B.; Han, J. Cereblon in health and disease. Pflugers Arch. 2016, 468, 1299–1309. [Google Scholar] [CrossRef]
- Desaphy, J.F.; Altamura, C.; Vicart, S.; Fontaine, B. Targeted Therapies for Skeletal Muscle Ion Channelopathies: Systematic Review and Steps Towards Precision Medicine. J. Neuromuscul. Dis. 2021, 8, 357–381. [Google Scholar] [CrossRef]
- Morelli, M.B.; Offidani, M.; Alesiani, F.; Discepoli, G.; Liberati, S.; Olivieri, A.; Santoni, M.; Santoni, G.; Leoni, P.; Nabissi, M. The effects of cannabidiol and its synergism with bortezomib in multiple myeloma cell lines. A role for transient receptor potential vanilloid type-2. Int. J. Cancer 2014, 134, 2534–2546. [Google Scholar] [CrossRef]
- Yanamandra, N.; Colaco, N.M.; Parquet, N.A.; Buzzeo, R.W.; Boulware, D.; Wright, G.; Perez, L.E.; Dalton, W.S.; Beaupre, D.M. Tipifarnib and bortezomib are synergistic and overcome cell adhesion-mediated drug resistance in multiple myeloma and acute myeloid leukemia. Clin. Cancer Res. 2006, 12, 591–599. [Google Scholar] [CrossRef] [Green Version]
- Coluzzi, F.; Rolke, R.; Mercadante, S. Pain Management in Patients with Multiple Myeloma: An Update. Cancers 2019, 11, 2037. [Google Scholar] [CrossRef] [Green Version]
- Liu, D.; Sun, M.; Xu, D.; Ma, X.; Gao, D.; Yu, H. Inhibition of TRPA1 and IL-6 signal alleviates neuropathic pain following chemotherapeutic bortezomib. Physiol. Res. 2019, 68, 845–855. [Google Scholar] [CrossRef]
- Li, C.; Deng, T.; Shang, Z.; Wang, D.; Xiao, Y. Blocking TRPA1 and TNF-α Signal Improves Bortezomib-Induced Neuropathic Pain. Cell. Physiol. Biochem. 2018, 51, 2098–2110. [Google Scholar] [CrossRef]
- Tomita, S.; Sekiguchi, F.; Deguchi, T.; Miyazaki, T.; Ikeda, Y.; Tsubota, M.; Yoshida, S.; Nguyen, H.D.; Okada, T.; Toyooka, N.; et al. Critical role of Cav3.2 T-type calcium channels in the peripheral neuropathy induced by bortezomib, a proteasome-inhibiting chemotherapeutic agent, in mice. Toxicology 2019, 413, 33–39. [Google Scholar] [CrossRef]
- Colvin, L.A.; Johnson, P.R.; Mitchell, R.; Fleetwood-Walker, S.M.; Fallon, M. From bench to bedside: A case of rapid reversal of bortezomib-induced neuropathic pain by the TRPM8 activator, menthol. J. Clin. Oncol. 2008, 26, 4519–4520. [Google Scholar] [CrossRef]
- Song, T.; Wang, L.; Gu, K.; Yang, Y.; Yang, L.; Ma, P.; Ma, X.; Zhao, J.; Yan, R.; Guan, J.; et al. Involvement of peripheral TRPV1 channels in the analgesic effects of thalidomide. Neurochem. Int. 2015, 85–86, 40–45. [Google Scholar] [CrossRef]
- Choi, T.Y.; Lee, S.H.; Kim, S.J.; Jo, Y.; Park, C.S.; Choi, S.Y. BK channel blocker paxilline attenuates thalidomide-caused synaptic and cognitive dysfunctions in mice. Sci. Rep. 2018, 8, 17653. [Google Scholar] [CrossRef]
- Hatem, S.; Attal, N.; Willer, J.C.; Bouhassira, D. Psychophysical study of the effects of topical application of menthol in healthy volunteers. Pain 2006, 122, 190–196. [Google Scholar] [CrossRef] [PubMed]
- Wasner, G.; Schattschneider, J.; Binder, A.; Baron, R. Topical menthol: A human model for cold pain by activation and sensitization of C nociceptors. Brain 2004, 127, 1159–1171. [Google Scholar] [CrossRef] [PubMed]
- Capatina, A.L.; Lagos, D.; Brackenbury, W.J. Targeting Ion Channels for Cancer Treatment: Current Progress and Future Challenges. In Targets of Cancer Diagnosis and Treatment; Stock, C., Pardo, L.A., Eds.; Reviews of Physiology, Biochemistry and Pharmacology; Springer: Cham, Switzerland, 2022; Volume 183, pp. 1–43. [Google Scholar] [CrossRef]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Saltarella, I.; Altamura, C.; Lamanuzzi, A.; Apollonio, B.; Vacca, A.; Frassanito, M.A.; Desaphy, J.-F. Ion Channels in Multiple Myeloma: Pathogenic Role and Therapeutic Perspectives. Int. J. Mol. Sci. 2022, 23, 7302. https://doi.org/10.3390/ijms23137302
Saltarella I, Altamura C, Lamanuzzi A, Apollonio B, Vacca A, Frassanito MA, Desaphy J-F. Ion Channels in Multiple Myeloma: Pathogenic Role and Therapeutic Perspectives. International Journal of Molecular Sciences. 2022; 23(13):7302. https://doi.org/10.3390/ijms23137302
Chicago/Turabian StyleSaltarella, Ilaria, Concetta Altamura, Aurelia Lamanuzzi, Benedetta Apollonio, Angelo Vacca, Maria Antonia Frassanito, and Jean-François Desaphy. 2022. "Ion Channels in Multiple Myeloma: Pathogenic Role and Therapeutic Perspectives" International Journal of Molecular Sciences 23, no. 13: 7302. https://doi.org/10.3390/ijms23137302