Clofazimine, Psora-4 and PAP-1, inhibitors of the potassium channel Kv1.3, as a new and selective therapeutic strategy in chronic lymphocytic leukemia

Leanza, Luigi; Trentin, Livio; Becker, Katrin Anne; Frezzato, Federica; Zoratti, Mario; Semenzato, Gianpietro; Gulbins, Erich; Szabó, Ildikò

doi:10.1038/leu.2013.56

Cited by 80 publications

(112 citation statements)

References 15 publications

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“…1 After an additional 48 h, clotrimazole reduced cell viability (determined by Annexin-V/7-AAD-negativity) most likely because of its inhibition of the cytochrome P450 enzymes, whereas TRAM-34, PAP-1 and Psora-4 lacked these effects Figure S6C). In contrast to our study, Leanza et al 14 recently described an apoptotic effect of Kv1.3 blockers on CLL cells by blockade of mitochondrial Kv1.3 channels and concluded that Kv1.3 blockers are eligible therapeutics for CLL. Because CLL cells lacking a supportive microenvironment activate cell death instead of mitotic programs, culture conditions can influence drug sensitivities.…”

Section: Opencontrasting

confidence: 99%

Targeting proliferation of chronic lymphocytic leukemia (CLL) cells through KCa3.1 blockade

et al. 2014

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Section: Opencontrasting

confidence: 99%

Targeting proliferation of chronic lymphocytic leukemia (CLL) cells through KCa3.1 blockade

et al. 2014

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“…Recently published data showed that the inhibition of Kv1.3 channels over-expressed in human neoplastic B cells in chronic lymphocytic leukemia (B-CLL) by Psora-4, PAP-1 and clofazimine induced apoptosis of these cells by activation of the intracellular (mitochondrial) pathway of this process [20]. In agreement with the results of previous studies, the more potent, but membrane-impermeant Kv1.3 channel inhibitor Stichodactyla helianthus (Shk) was ineffective.…”

Section: Kv13 Channels In Cancer Diagnostics and Therapysupporting

confidence: 81%

“…Moreover, the ability to induce apoptosis of B-CLL cells was significantly augmented when the inhibitors were coapplied with inhibitors of membrane multi-drug resistance transporters. Finally, clofazimine was the most effective inducer of apoptosis of B-CLL cells (EC 50 ~ 1 μM in the presence of multi-drug resistance transporter inhibitors compared to > 10 μM for both Psora-4 and PAP-1) [20]. Interestingly, an application of the Kv1.3 channel inhibitors caused a selective apoptosis of B-CLL cells without affecting T lymphocytes from patients with leukemia and B and T lymphocytes from healthy donors.…”

Section: Kv13 Channels In Cancer Diagnostics and Therapymentioning

confidence: 95%

“…Recently, Kv1.3 channels are considered a new, potentially attractive molecular target in both cancer diagnostics and therapy [6][7][8][17][18][19][20]. First of all, several studies have demonstrated altered expression of Kv1.3 in some cancer specimens in comparison with normal tissue [6-8, 17, 18].…”

Section: Kv13 Channels In Cancer Diagnostics and Therapymentioning

confidence: 99%

“…First of all, several studies have demonstrated altered expression of Kv1.3 in some cancer specimens in comparison with normal tissue [6-8, 17, 18]. An increased expression of Kv1.3 channels was observed in the case of breast, colon, smooth muscle (leiomyosarcoma), skeletal muscle (alveolar rhabdomyosarcoma) and lymph node cancer [8,17] and in mature neoplastic B cells in chronic lymphocytic leukemia (B-CLL) [20]. A significantly increased expression of Kv1.3 channels that was positively correlated with tumor aggressiveness was recently observed in the case of leiomyosarcoma and alveolar rhabdomyosarcoma [8,18].…”

Section: Kv13 Channels In Cancer Diagnostics and Therapymentioning

confidence: 99%

See 2 more Smart Citations

Voltage-Gated Ptassium Channels Kv1.3 - Potentially New Molecular Target in Cancer Diagnostics and Therapy

Teisseyre¹,

Gąsiorowska²,

Michalak³

2015

Adv Clin Exp Med

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Voltage-gated potassium channels, Kv1.3, which were discovered in 1984, are integral membrane proteins which are activated ("open") upon change of the cell membrane potential, enabling a passive flux of potassium ions across the cell membrane. The channels are expressed in many different tissues, both normal and cancer. Since 2005 it has been known that the channels are expressed not only in the plasma membrane, but also in the inner mitochondrial membrane. The activity of Kv1.3 channels plays an important role, among others, in setting the cell resting membrane potential, cell proliferation, apoptosis and volume regulation. For some years, these channels have been considered a potentially new molecular target in both the diagnostics and therapy of some cancer diseases. This review article focuses on: 1) changes of expression of the channels in cancer disorders with special regard to correlations between the channels' expression and stage of the disease, 2) influence of inhibitors of Kv1.3 channels on proliferation and apoptosis of cancer cells, 3) possible future applications of Kv1.3 channels' inhibitors in therapy of some cancer diseases. In the last section, the results of studies performed in our Laboratory of Bioelectricity on the influence of selected biologically active plant-derived compounds from the groups of flavonoids and stilbenes and their natural and synthetic derivatives on the activity of Kv1.3 channels in normal and cancer cells are reviewed. A possible application of some compounds from these groups to support therapy of cancer diseases, such as breast, colon and lymph node cancer, and melanoma or chronic lymphocytic leukemia (B-CLL), is announced (Adv Clin Exp Med 2015, 24, 3, 517-524).

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Toward Hijacking Bioelectricity in Cancer to Develop New Bioelectronic Medicine

Robinson

Jain

Sherman

et al. 2021

Advanced Therapeutics

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Bioelectronic medicine is a treatment modality that uses electricity to treat disease by altering the body's electrical communication systems. All cells are electrically active, in that they possess bioelectric circuitry generating a resting membrane potential and endogenous electric fields that influence cell functions and communication. There is now an accepted paradigm that cancer is characterized by malfunctions in cells' bioelectrical circuitry. This yields opportunities for bioelectronic medicine as novel treatments for cancer by manipulating its bioelectrical properties. To highlight the possibilities a bioelectrical approach can offer cancer therapy, the relevance of bioelectrical activity in cancer is reviewed and also how such activity can be hijacked in novel treatments. This includes sensing or measuring the electrical activity of cells for diagnostic and prognostic applications, controlling or altering bioelectricity including both ionic and faradaic current processes, and eliciting morphological changes using electric fields. Importantly, key links between cellular ionic and faradaic processes that contribute to cancer phenotypes are presented, which if considered and understood as a whole, can bring broad-reaching improvements to cancer therapy.

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Clofazimine, Psora-4 and PAP-1, inhibitors of the potassium channel Kv1.3, as a new and selective therapeutic strategy in chronic lymphocytic leukemia

Cited by 80 publications

References 15 publications

Targeting proliferation of chronic lymphocytic leukemia (CLL) cells through KCa3.1 blockade

Targeting proliferation of chronic lymphocytic leukemia (CLL) cells through KCa3.1 blockade

Voltage-Gated Ptassium Channels Kv1.3 - Potentially New Molecular Target in Cancer Diagnostics and Therapy

Toward Hijacking Bioelectricity in Cancer to Develop New Bioelectronic Medicine

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