Potassium channels, tumorigenesis and targeted drugs - 29/04/23
, Chenglai Xia b, c, ⁎ Abstract |
Potassium channels play an important role in human physiological function. Recently, various molecular mechanisms have implicated abnormal functioning of potassium channels in the proliferation, migration, invasion, apoptosis, and cancer stem cell phenotype formation. Potassium channels also mediate the association of tumor cells with the tumor microenvironment. Meanwhile, potassium channels are important targets for cancer chemotherapy. A variety of drugs exert anti-cancer effects by modulating potassium channels in tumor cells. Therefore, there is a need to understand how potassium channels participate in tumor development and progression, which could reveal new, novel targets for cancer diagnosis and treatment. This review summarizes the roles of voltage-gated potassium channels, calcium-activated potassium channels, inwardly rectifying potassium channels, and two-pore domain potassium channels in tumorigenesis and the underlying mechanism of potassium channel-targeted drugs. Therefore, the study lays the foundation for rational and effective drug design and individualized clinical therapeutics.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Structure of potassium channels and targeting drugs in cancer. The Kv/IK/SK channel has six transmembrane helices (S1–S6) with a pore helix (P) between segments S5 and S6. The first four helices (S1–S4) form the voltage-sensing domain. The last two helices (S5–S6) form the pore domain. Blockers of the Kv channel include 4-aminopyridine, quinidine, tetraethylammonium, amiodarone, FS48 protein, KAaH 1, mevastatin, simvastatin, acacetin, chrysin, psoralen derivatives, blood-depressing substances, astemizole, chloroquine, new diarylamine, procyanidin B1, tetrandrine, nutlin-3, and berberine. Blockers of IK channels include clotrimazole, triarylmethane-34, senicapo, vigabatrin, and piperine. The transmembrane helices of the BK channel contain an extra transmembrane helix called S0. The voltage-sensing domain of the BK channel is mainly composed of helices S1–S4 and the S5–S6 helices constitute the pore domain. Blockers of BK channels include paxilline, tetraethylammonium, iberiotoxin, and penitrem A. Kir channels have only two transmembrane segments called the outer helix (M1) and the inner helix (M2). Kir channels form tetramers, where M2 contributes to the pore domain. Amiodarone and glibenclamide are blockers of the Kir channel, and minoxidil is an activator of the Kir channel. The K2P channel has four transmembrane segments (M1-M4), two pore helices (P1 and P2), and a unique extracellular cap structure (cap helices C1 and C2). The first pore domain includes M1, C1, C2, P1, and M2. The second pore domain includes M3, P2, and M4. Withaferin A is a blocker of the K2P channel.
Structure of potassium channels and targeting drugs in cancer. The Kv/IK/SK channel has six transmembrane helices (S1–S6) with a pore helix (P) between segments S5 and S6. The first four helices (S1–S4) form the voltage-sensing domain. The last two helices (S5–S6) form the pore domain. Blockers of the Kv channel include 4-aminopyridine, quinidine, tetraethylammonium, amiodarone, FS48 protein, KAaH 1, mevastatin, simvastatin, acacetin, chrysin, psoralen derivatives, blood-depressing substances, astemizole, chloroquine, new diarylamine, procyanidin B1, tetrandrine, nutlin-3, and berberine. Blockers of IK channels include clotrimazole, triarylmethane-34, senicapo, vigabatrin, and piperine. The transmembrane helices of the BK channel contain an extra transmembrane helix called S0. The voltage-sensing domain of the BK channel is mainly composed of helices S1–S4 and the S5–S6 helices constitute the pore domain. Blockers of BK channels include paxilline, tetraethylammonium, iberiotoxin, and penitrem A. Kir channels have only two transmembrane segments called the outer helix (M1) and the inner helix (M2). Kir channels form tetramers, where M2 contributes to the pore domain. Amiodarone and glibenclamide are blockers of the Kir channel, and minoxidil is an activator of the Kir channel. The K2P channel has four transmembrane segments (M1-M4), two pore helices (P1 and P2), and a unique extracellular cap structure (cap helices C1 and C2). The first pore domain includes M1, C1, C2, P1, and M2. The second pore domain includes M3, P2, and M4. Withaferin A is a blocker of the K2P channel.ga1Le texte complet de cet article est disponible en PDF.
Highlights |
• | Potassium channels play an important role in tumorigenesis. |
• | Potassium channels are involved in tumor proliferation, metastasis, and apoptosis through multiple molecular pathways. |
• | Drugs exert anticancer effects by targeting potassium channels. |
Abbreviations : AKT, Bcl-2, Bcl-xl, ERK, KCa, KCa 1.1/BK, KCa 3.1/IK, KCNJ, KCNK, KCNN, Kir, Kv, K2P, MAPK, MEK, NF-κB, PI3K, SK, VGKC
Keywords : Potassium channel, Tumor, Targeted drugs, Molecular mechanism, Antitumor therapy
Plan
Vol 162
Article 114673- juin 2023 Retour au numéro
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