Table 1.
Ion channels blockers and openers tested in OC and their biological effects.
| Drug | Clinical Indications | Ion Channel Target | Biological Effects in OC | Other Known Effects/Uses | Ref. |
|---|---|---|---|---|---|
| TTX | Natural toxin | VGSC blocker | In vitro: reduction of OC cells migration and invasion | - | [28] |
| EPA | Omega-3 fatty acids | Nav1.5 blocker | In vitro: suppression of growth and reduction of invasivity | Cardioprotective effects, cognitive function improvement, fatigue recovery and endurance performance improvement, maintenance of immune function | [42,43,51] |
| Topiramate | Antiepileptic drug | VGSC blocker | In vitro: reduction of cell proliferation and migration | Off-label uses: neuropathic pain, psychotropic drug-induced weight gain, alcohol use disorders with tobacco dependence, binge eating disorder, bulimia nervosa, obesity with hypertension, adjunctive therapy in bipolar disorder, unipolar depression, borderline personality disorder, obsessive-compulsive disorder, posttraumatic stress disorder, Tourette syndrome, Prader-Willie syndrome, essential tremor. Carbonic anhydrase inhibitor |
[45,52] |
| Bupivacaine | Local anesthetic drug | VGSC blocker | In vitro: reduction of OC cell proliferation and migration | - | [47] |
| Lidocaine | Local anesthetic drug | VGSC blocker | In vitro: reduction of OC cell proliferation, migration, and invasion; increase of cisplatin efficiency in OC cells In vivo: increase of cisplatin efficiency in a murine ovarian metastatic model |
Intractable cough and asthma, and chronic (including neuropathic) pain. | [48,53,54] |
| E3Ab | Polyclonal antibody | Nav1.5 | In vitro: reduction of OC cell proliferation and invasive capacity | - | [49,50] |
| Imipramine | Tricyclic antidepressant drug | Eag blocker | In vitro: early apoptosis | Inhibitor of the reuptake of norepinephrine and serotonin; Antagonist of D2 dopamine, muscarinic, α1 and α2 adrenergic, and H1 histamine receptors. Off-label uses: chronic neuropathic pain and panic disorder. |
[18,55,56,57] |
| Clofilium | Antiarrhythmic drug | Eag blocker | In vitro: early apoptosis | In mammalian cardiac myocytes, clofilium also affects Na+ and L-type Ca2+ currents. NMDA glutamate Rc antagonist. | [55,58,59] |
| Berberine | Natural alkaloid | hERG blocker | In vitro: inhibition of OC cells proliferation | Antiviral activity against Herpes simplex virus 1 and 2 by modulating host cell activation of the NF-kB and MAPK pathway. | [60,61] |
| mAb56 | Monoclonal antibody | Eag blocker | In vitro: inhibition of OC cell growth | - | [62] |
| Tetrandrine | Natural alkaloid | BK channels blocker | In vitro: reduction of OC cell proliferation by inducing G1 phase arrest and accelerating apoptosis | Anti-hypertensive effects through T-type Ca2+ channel blocking; Anti-inflammatory, immunosuppressant and antiallergic effects mediated by tetrandrine inhibition of ILs, TNF-a, prostaglandin, cycloxygenase-2 and T cells; Antioxidant activity by scavenging the superoxide anion radicals; Anticancer agent; Antimicrobial activity. |
[63,64] |
| Iberiotoxin | Natural toxin | BK channels blocker | In vitro: reduction of OC cell proliferation by inducing G1 phase arrest | - | [63] |
| NS1619 | Experimental compound | BK channels opener | In vitro: inhibition of OC cell proliferation by cell shrinkage and release of cytochrome c and activation of caspase, inducing apoptosis | Protection of cardiac muscle against ischaemia and reperfusion injury; Cytoprotective effect through directly inhibition of SERCA activity. | [65,66] |
| Minoxidil | Antihypertensive drug | Kir6.2/SUR2 activator | In vitro: reduction of OC cell proliferation In vivo: Reduction of tumor growth in OC xenograft model |
Treatment for androgenetic alopecia and off-label uses for other hair loss conditions | [67,68] |
| Methanandamide | Cannabinoid receptor agonist |
TASK-3 blocker | In vitro: reduction of OC cell proliferation and increasing in apoptosis | Anti- and pronociceptive effects by activating both cannabinoid (CB1) and vanilloid (TRPV1) receptors of nociceptive primary afferents. | [69,70] |
| Zinc | Chemical element | TASK-3 blocker | In vitro: reduction of OC cells proliferation and increase of apoptosis | Anti-diarrheal effects by inhibiting cyclic adenosine monophosphate (cAMP), calcium, and nitric oxide; antioxidative and antimicrobial effects through the antioxidant activity of cysteine-rich metallothioneins | [69,71] |
| Curcumin | Natural phenolic antioxidant | TREK-1 blocker | In vitro: reduction of OC cells proliferation and increase of late apoptosis processes | Antioxidant, anti-inflammatory, antimicrobial, antidiabetic, anti-aging effects. Multi-ion channel blocker such as voltage-gated Na+, Ca2+, K+ channels Activation of various TRP channels. | [72,73,74,75] |
| Amphotericin | Antifungal | K+ ionophore | In vitro: sensitize cells to cisplatin and other platinum-based agents | Production of free radicals and subsequently oxidative damage; stimulation of phagocytic cells | [76,77] |
| Bumetanide | Diuretic | Na-K-Cl cotransporter inhibitor | In vitro: boost cisplatin-induced apoptosis | - | [78] |
| Niflumic acid | Nonsteroidal anti-inflammatory drug | CLC and VRAC blocker |
In vitro: inhibition of OC cell proliferation, adhesion, and invasion | Blocking effect on TRPV1 channels, T-type calcium channels, CFTR, TRPA1, and several voltage-gated potassium channels. | [79,80,81,82,83,84] |
| CLCA1 blocker | In vitro: Reduced ability of OC cells to form multicellular aggregates | [85] | |||
| Tamoxifen | Non-steroidal antiestrogen | CLC and VRAC blocker | In vitro: Inhibition of OC cell proliferation and suppression of cell adhesion and invasion | Treatment of hormone-sensitive breast cancer | [79] |
| Nitro-2-(3-phenylpropylamino)-benzoate (NPPB) | Experimental compound | CLC and VRAC blocker | In vitro: Inhibition of OC cell proliferation and suppression of cell adhesion and invasion | - | [80,86] |
| Mibefradil | In a phase I clinical trial for the treatment of gliomas | T-type Ca2+ channel blocker | In vitro: Alteration of cell-cycle progression, slowing of proliferation, and increase of cell death processes Inhibition of growth and increase of apoptosis in platinum-resistant OC cells In vivo: mibefradil sensitizes platinum-resistant OC to carboplatin in a mouse model of peritoneal metastasis due to OC |
Blocking effects on Orai channels (204 Li et al., 2019); Inhibition of CYP3A cytochrome (205 Foti et al., 2011); inhibition of Kv10.1 (206 Gómez-Lagunas et al., 2017) In a phase I clinical trial for the treatment of gliomas |
[87,88,89,90,91,92] |
| Nifedipine | antihypertensive and antianginal | Voltage-gated Ca2+ channel blocker | In vitro: Inhibition of LPA-induced OC cell migration and adhesion; Increase of cytosolic calcium levels in A2780 cells |
Off-label uses: Raynaud phenomenon; Tocolysis; Distal ureteric calculi |
[93,94,95,96] |
| Sulforaphane (SFN) | Natural isothiocyanate compound | IP3R1 | In vitro: Inhibition of OC cell proliferation | Antioxidant, antidiabetic, antiinflammatory effects | [97,98,99,100] |
| Melatonin | Hormone | IP3R1 | In vitro: Inhibition of OC cell proliferation | Delayed sleep phase syndrome treatment | [101,102] |
| 3,4-dihydroquinazoline derivatives | Experimental compounds | T-type Ca2+ channel blocker | In vitro: Alteration of cell-cycle progression, slowing of proliferation, and increased cell death processes | - | [88] |
| lomerizine | Antimigrainous drug | L and T-type Ca2+ channel blocker | In vitro: reduction of stemness and induction of apoptosis in CSCs | Antihistamine and anti-serotonin effects | [103,104] |
| manidipine, lacidipine, benidipine | Antihypertensive drugs | L-type Ca2+ channel blockers | In vitro: reduction of stemness and induction of apoptosis in CSCs | - | [103] |
| Soricidin, SOR-C13, and SOR-C27 | Natural oligopeptide and analogs | TRPV6 | In vivo: reduction of growth of OC cell tumor xenografts in mice | - | [105] |