TY - EJOU
AU - SHAHRANI, MESFER AL
AU - RAJAGOPALAN, PRASANNA
AU - ABOHASSAN, MOHAMMAD
AU - ALSHAHRANI, MOHAMMAD
AU - ALRAEY, YASSER
AU - GAHTANI, REEM M.
AU - RADHAKRISHNAN, SURESH
AU - DAGREERY, KHLOOD
TI - Anticancer efficacy of 3-(4-isopropyl) benzylidene-8-ethoxy, 6-methyl, chroman-4-one (SBL-060), a novel, dual, estrogen receptor-Akt kinase inhibitor in acute myeloid leukemia cells
T2 - Oncology Research
PY - 2021
VL - 29
IS - 3
SN - 1555-3906
AB - Estrogen receptor (ER) α is expressed in a subset of patient-derived acute myeloid leukemia (AML) cells,
whereas Akt is predominantly expressed in most types of AML. Targeting AML with dual inhibitors is a novel
approach to combat the disease. Herein, we examined a novel small molecule, 3-(4-isopropyl) benzylidene-8-ethoxy,6-
methyl, chroman-4-one (SBL-060), capable of targeting AML cells by inhibiting ERα and Akt kinase. The chemical
properties of SBL-060 were identified by proton nuclear magnetic resonance (1
H-NMR), 13C-NMR, and mass
spectroscopy. In silico docking was performed using an automated protocol with AutoDock-VINA. THP-1 and HL-60
cell lines were differentiated using phorbol 12-myristate 13-acetate. ERα inhibition was assessed using ELISA. The
MTT assay assessed cell viability. Flow cytometry was performed for cell cycle, apoptosis, and p-Akt analyses.
Chemical analysis identified the compound as 3-(4-isopropyl) benzylidene-8-ethoxy,6-methyl, chroman-4-one, which
showed high binding efficacy toward ER, with a ΔGbinding score of −7.4 kcal/mol. SBL-060 inhibited ERα, exhibiting
IC50 values of 448 and 374.3 nM in THP-1 and HL-60 cells, respectively. Regarding inhibited cell proliferation, GI50
values of SBL-060 were 244.1 and 189.9 nM for THP-1 and HL-60 cells, respectively. In addition, a dose-dependent
increase in sub G0/G1 phase cell cycle arrest and total apoptosis was observed after treatment with SBL-060 in both
cell types. SBL-060 also dose-dependently increased the p-Akt-positive populations in both THP-1 and HL-60 cells.
Our results indicate that SBL-060 has excellent efficacy against differentiated AML cell types by inhibiting ER and Akt
kinase, warranting further preclinical evaluations.
KW - Akt kinase
KW - AML
KW - THP-1
KW - HL-60
KW - Estrogen receptor
KW - Benzylidene compounds
DO - 10.32604/or.2022.03539