title: Curcumin blocks Kv11.1 (erg) potassium current and slows proliferation in the infant acute monocytic leukemia cell line THP-1.
abstract: Acute Myeloid Leukemia (AML) accounts for approximately one fifth of all childhood leukemia yet is responsible for a significant proportion of morbidity and mortality in this population. For this reason, research to identify novel targets for the development of effective AML therapeutics has intensified in the recent past. The THP-1 cell line, which was originally established from an infant diagnosed with AML, provides an experimental model for functional, pre-clinical therapeutics and target identification studies of AML. Here we show the expression of the voltage gated potassium channel Kv11.1 in THP-1 cells as opposed to normal hematopoietic stem cells. In addition, curcumin, a natural polyphenol derived from the plant Curcuma longa, effectively blocked Kv11.1 activity and also inhibited the proliferation of these cells. Curcumin was rapidly internalized by THP-1 cells and possibly exerts potential growth inhibitory activity by interacting with intracellular epitopes of the ion channel. Inhibition of ionic currents carried by Kv11.1 resulted in depolarization of cell membrane potential. We propose that the inhibition of Kv11.1 activity by curcumin may lead to interference with leukemic cell physiology and consequently the suppression of survival and proliferation of AML cells.
authors.affiliation: Faculty of Kinesiology, University of Calgary, Calgary, AB, Canada. ubanderali@kin.ucalgary.ca
authors.forename: Umberto
authors.initials: U
authors.lastname: Banderali
authors.forename: Darrell
authors.initials: D
authors.lastname: Belke
authors.forename: Anjali
authors.initials: A
authors.lastname: Singh
authors.forename: Aarthi
authors.initials: A
authors.lastname: Jayanthan
authors.forename: Wayne R
authors.initials: WR
authors.lastname: Giles
authors.forename: Aru
authors.initials: A
authors.lastname: Narendran
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D049109:Cell Proliferation; D030024:Curcuma / Q000737:chemistry; D003474:Curcumin / Q000494:pharmacology* / Q000627:therapeutic use; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D011188:Potassium / Q000378:metabolism*; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D020033:Protein Isoforms; D003474:Curcumin; D011188:Potassium