Cell Cycle Regulation by Ca2+-Activated K+ (BK) Channels Modulators in SH-SY5Y Neuroblastoma Cells
AbstractThe effects of Ca2+-activated K+ (BK) channel modulation by Paxilline (PAX) (10−7–10−4 M), Iberiotoxin (IbTX) (0.1–1 × 10−6 M) and Resveratrol (RESV) (1–2 × 10−4 M) on cell cycle and proliferation, AKT1pSer473 phosphorylation, cell diameter, and BK currents were investigated in SH-SY5Y cells using Operetta-high-content-Imaging-System, ELISA-assay, impedentiometric counting method and patch-clamp technique, respectively. IbTX (4 × 10−7 M), PAX (5 × 10−5 M) and RESV (10−4 M) caused a maximal decrease of the outward K+ current at +30 mV (Vm) of −38.3 ± 10%, −31.9 ± 9% and −43 ± 8%, respectively, which was not reversible following washout and cell depolarization. After 6h of incubation, the drugs concentration dependently reduced proliferation. A maximal reduction of cell proliferation, respectively of −60 ± 8% for RESV (2 × 10−4 M) (IC50 = 1.50 × 10−4 M), −65 ± 6% for IbTX (10−6 M) (IC50 = 5 × 10−7 M), −97 ± 6% for PAX (1 × 10−4 M) (IC50 = 1.06 × 10−5 M) and AKT1pser473 dephosphorylation was observed. PAX induced a G1/G2 accumulation and contraction of the S-phase, reducing the nuclear area and cell diameter. IbTX induced G1 contraction and G2 accumulation reducing diameter. RESV induced G2 accumulation and S contraction reducing diameter. These drugs share common actions leading to a block of the surface membrane BK channels with cell depolarization and calcium influx, AKT1pser473 dephosphorylation by calcium-dependent phosphatase, accumulation in the G2 phase, and a reduction of diameter and proliferation. In addition, the PAX action against nuclear membrane BK channels potentiates its antiproliferative effects with early apoptosis. View Full-Text
Share & Cite This Article
Maqoud, F.; Curci, A.; Scala, R.; Pannunzio, A.; Campanella, F.; Coluccia, M.; Passantino, G.; Zizzo, N.; Tricarico, D. Cell Cycle Regulation by Ca2+-Activated K+ (BK) Channels Modulators in SH-SY5Y Neuroblastoma Cells. Int. J. Mol. Sci. 2018, 19, 2442.
Maqoud F, Curci A, Scala R, Pannunzio A, Campanella F, Coluccia M, Passantino G, Zizzo N, Tricarico D. Cell Cycle Regulation by Ca2+-Activated K+ (BK) Channels Modulators in SH-SY5Y Neuroblastoma Cells. International Journal of Molecular Sciences. 2018; 19(8):2442.Chicago/Turabian Style
Maqoud, Fatima; Curci, Angela; Scala, Rosa; Pannunzio, Alessandra; Campanella, Federica; Coluccia, Mauro; Passantino, Giuseppe; Zizzo, Nicola; Tricarico, Domenico. 2018. "Cell Cycle Regulation by Ca2+-Activated K+ (BK) Channels Modulators in SH-SY5Y Neuroblastoma Cells." Int. J. Mol. Sci. 19, no. 8: 2442.
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.