Curcumin promotes cell cycle arrest and apoptosis of acute myeloid leukemia cells by inactivating AKT

Zhou, Hao; Ning, Yichong; Zeng, Gaofeng; Zhou, Chang; Ding, Xiaofeng

doi:10.3892/or.2021.7962

Cited by 32 publications

(19 citation statements)

References 31 publications

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“…This computational efficacy was undoubtedly translated in our in vitro findings, exhibiting the dose-dependent inhibition of Akt phosphorylation by SBL-060 in both AML cell types. Previous studies have shown that cell cycle alterations and apoptosis induction can occur by inhibiting Akt kinase in AML cells [27][28][29]. The results of the present study corroborate those of previous reports, suggesting the efficacy of SBL-060 against AML cells by inhibiting Akt, thus hindering the regular cell cycle and inducing cellular apoptosis.…”

Section: Discussionsupporting

confidence: 91%

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

Shahrani¹,

Rajagopalan²,

Abohassan³

et al. 2021

Oncology Research

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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,6methyl, 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), 13 C-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 ΔG binding score of −7.4 kcal/mol. SBL-060 inhibited ERα, exhibiting IC 50 values of 448 and 374.3 nM in THP-1 and HL-60 cells, respectively. Regarding inhibited cell proliferation, GI 50 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 G 0 /G 1 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.

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Section: Discussionsupporting

confidence: 91%

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

Shahrani¹,

Rajagopalan²,

Abohassan³

et al. 2021

Oncology Research

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“…Based on the cell viability assay, we wondered whether high Cur dosages induced a proliferation arrest or cell death. It is known that Cur can elicit different effects on several cellular processes such as cell death, inflammation, oxidative stress, angiogenesis, and autophagy, depending on the dose administered [ 6 , 8 , 9 , 12 , 21 , 22 , 23 , 24 , 25 , 26 ]. Hence, we used flow cytometry for the analysis in apoptosis levels.…”

Section: Resultsmentioning

confidence: 99%

New Insights into Dose-Dependent Effects of Curcumin on ARPE-19 Cells

Carozza

Tisi

Capozzo

et al. 2022

IJMS

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Opposing dose-dependent effects of curcumin (Cur) have been documented in Retinal Pigment Epithelium (RPE); therefore, to shed the light on the mechanisms of action is crucial for ophthalmic applications. On this basis we explored new insights about the dose-dependent mechanisms triggered by Cur in human retinal pigment epithelial cells (ARPE-19). Three concentrations (0.01 mM; 0.05 mM; 0.1 mM) of Cur were tested, followed by morphological, molecular, and functional analysis of the cells. Cur 0.01 mM promotes a significant increase in cell proliferation, not affecting cell cycle progression and apoptosis; by contrast, Cur 0.05 mM and 0.1 mM block cellular proliferation and trigger S-phase cell cycle arrest without inducing apoptosis. The observation of neuronal-like morphological changes in Cur 0.05 mM and 0.1 mM were not associated with neuronal differentiation, as observed by the quantification of Neurofilament-200 and by the analysis of voltage-dependent currents by patch clamp. Evaluation of autophagic markers LC3BII and p62 revealed significant modulations, suggesting an important activation of autophagy in ARPE-19 cells treated with Cur 0.05 mM and Cur 0.1 mM; conversely, Cur 0.01 mM did not affect autophagy. Altogether, our findings show new dose-dependent mechanisms of action of Cur that suggest a wide therapeutic application in ocular diseases with different pathogenesis (i.e., proliferative vitreoretinopathy or Age-Related Macular Degeneration).

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“…The sequence of siTsc1: GCUUUGACUCUCCCUUCUA [ 15 ]. SC-79 (10 μM; MCE, Shanghai, China) was used to treat PASMCs for 24 h [ 16 ].…”

Section: Methodsmentioning

confidence: 99%

Decrease in Tripartite Motif Containing 24 suppresses hypoxia-induced proliferation and migration of pulmonary arterial smooth muscle cells via the AKT/mammalian target of rapamycin complex 1 pathway

Xu¹,

Zhong²,

Wang³

2022

Bioengineered

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Tripartite Motif Containing 24 (TRIM24) is an oncogenic protein and promotes proliferation in several cancer cell lines. Nevertheless, the role of TRIM24 in proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) remains to be clarified. The current study was aimed to reveal the role of TRIM24 in proliferation and migration of PASMCs during the development of pulmonary arterial hypertension (PAH). In pulmonary arteries (PAs) of chronic hypoxia-PAH (CH-PAH) mice and PASMCs challenged with hypoxia, the expression of TRIM24 was increased. Silencing TRIM24 by Trim24 short hair RNA (shTrim24) suppressed hypoxia-induced increase in Ki-67 positive PASMCs and wound-healing rate. Furthermore, hypoxia caused enhanced phosphorylation of AKT and two major effectors of mammalian target of rapamycin complex 1 (mTORC1), S6 and 4EBP1 in PASMCs. The enhancement was then attenuated after silencing TRIM24. Both restoring mTORC1 activity and AKT reactivation abolished silencing TRIM24-mediated inhibition of proliferation and migration of PASMCs. Additionally, AKT reactivation also reversed the declined phosphorylation of S6 and 4EBP1 induced by shTrim24. In conclusion, TRIM24 is involved in the excessive proliferation and migration of PASMCs after hypoxic stimulus during PAH. The mechanism of TRIM24-mediated regulation of PASMCs is partly illustrated by promoting activity of AKT/mTORC1 signaling pathway.

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Curcumin promotes cell cycle arrest and apoptosis of acute myeloid leukemia cells by inactivating AKT

Cited by 32 publications

References 31 publications

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

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

New Insights into Dose-Dependent Effects of Curcumin on ARPE-19 Cells

Decrease in Tripartite Motif Containing 24 suppresses hypoxia-induced proliferation and migration of pulmonary arterial smooth muscle cells via the AKT/mammalian target of rapamycin complex 1 pathway

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