Anti-leukemic principle(s) from Momordica charantia seeds induce differentiation of HL-60 cells through ERK/MAPK signalling pathway

Sharma, Jeetesh; Prabha, Punit; Sharma, Rohit; Gupta, Sanjay; Dixit, Aparna

doi:10.1007/s10616-022-00547-x

Cited by 3 publications

(4 citation statements)

References 53 publications

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“…Indeed, many potent myeloid differentiation inducers including ursolic acid [28], Jasmonates, potent lipid regulators in plants [29], Momordica charantia seeds [30], Vibsanin A, a novel protein kinase C activator [31], diptoindonesin G (Dip G), a natural resveratrol aneuploid [32], human epidermal growth factor receptor 2 (HER2) inhibitor TAK165 [33], and CSF2RA, and (L) IL3RA. Relative mRNA expressions were calculated from the copy number of the target gene adjusted by GAPDH, in each TCN-treated sample (2.5, 5, 10 μM), which were divided by the control sample values.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, many potent myeloid differentiation inducers including ursolic acid [ 28 ], Jasmonates, potent lipid regulators in plants [ 29 ], Momordica charantia seeds [ 30 ], Vibsanin A, a novel protein kinase C activator [ 31 ], diptoindonesin G (Dip G), a natural resveratrol aneuploid [ 32 ], human epidermal growth factor receptor 2 (HER2) inhibitor TAK165 [ 33 ], and staurosporine, a protein kinase C pan-inhibitor [ 34 ], were reported to activate the Raf/MEK/ERK pathway. These agents mainly activate ERK/MAPK [ 28 – 34 ] and the downstream STAT1 [ 32 , 33 ], either alone or in combination with ATRA [ 34 ], to induce the monocytic and/or granulocytic differentiation of myeloid cell lines including HL-60 [ 28 – 32 ], NB4 [ 33 ], U937 [ 34 ], or primary AML samples [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

“…staurosporine, a protein kinase C pan-inhibitor [34], were reported to activate the Raf/MEK/ ERK pathway. These agents mainly activate ERK/MAPK [28][29][30][31][32][33][34] and the downstream STAT1 [32,33], either alone or in combination with ATRA [34], to induce the monocytic and/or granulocytic differentiation of myeloid cell lines including HL-60 [28][29][30][31][32], NB4 [33], U937 [34], or primary AML samples [32].…”

Section: Plos Onementioning

confidence: 99%

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Identification of triciribine as a novel myeloid cell differentiation inducer

Suzuki,

Sato-Nagaoka

et al. 2024

PLoS ONE

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Differentiation therapy using all-trans retinoic acid (ATRA) for acute promyelocytic leukemia (APL) is well established. However, because the narrow application and tolerance development of ATRA need to be improved, we searched for another efficient myeloid differentiation inducer. Kinase activation is involved in leukemia biology and differentiation block. To identify novel myeloid differentiation inducers, we used a Kinase Inhibitor Screening Library. Using a nitroblue tetrazolium dye reduction assay and real-time quantitative PCR using NB4 APL cells, we revealed that, PD169316, SB203580, SB202190 (p38 MAPK inhibitor), and triciribine (TCN) (Akt inhibitor) potently increased the expression of CD11b. We focused on TCN because it was reported to be well tolerated by patients with advanced hematological malignancies. Nuclear/cytoplasmic (N/C) ratio was significantly decreased, and myelomonocytic markers (CD11b and CD11c) were potently induced by TCN in both NB4 and acute myeloid leukemia (AML) M2 derived HL-60 cells. Western blot analysis using NB4 cells demonstrated that TCN promoted ERK1/2 phosphorylation, whereas p38 MAPK phosphorylation was not affected, suggesting that activation of the ERK pathway is involved in TCN-induced differentiation. We further examined that whether ATRA may affect phosphorylation of ERK and p38, and found that there was no obvious effect, suggesting that ATRA induced differentiation is different from TCN effect. To reveal the molecular mechanisms involved in TCN-induced differentiation, we performed microarray analysis. Pathway analysis using DAVID software indicated that “hematopoietic cell lineage” and “cytokine-cytokine receptor interaction” pathways were enriched with high significance. Real-time PCR analysis demonstrated that components of these pathways including IL1β, CD3D, IL5RA, ITGA6, CD44, ITGA2B, CD37, CD9, CSF2RA, and IL3RA, were upregulated by TCN-induced differentiation. Collectively, we identified TCN as a novel myeloid cell differentiation inducer, and trials of TCN for APL and non-APL leukemia are worthy of exploration in the future.

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Section: Discussionmentioning

confidence: 99%

“…Indeed, many potent myeloid differentiation inducers including ursolic acid [ 28 ], Jasmonates, potent lipid regulators in plants [ 29 ], Momordica charantia seeds [ 30 ], Vibsanin A, a novel protein kinase C activator [ 31 ], diptoindonesin G (Dip G), a natural resveratrol aneuploid [ 32 ], human epidermal growth factor receptor 2 (HER2) inhibitor TAK165 [ 33 ], and staurosporine, a protein kinase C pan-inhibitor [ 34 ], were reported to activate the Raf/MEK/ERK pathway. These agents mainly activate ERK/MAPK [ 28 – 34 ] and the downstream STAT1 [ 32 , 33 ], either alone or in combination with ATRA [ 34 ], to induce the monocytic and/or granulocytic differentiation of myeloid cell lines including HL-60 [ 28 – 32 ], NB4 [ 33 ], U937 [ 34 ], or primary AML samples [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Section: Plos Onementioning

confidence: 99%

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Identification of triciribine as a novel myeloid cell differentiation inducer

Suzuki,

Sato-Nagaoka

et al. 2024

PLoS ONE

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“… 26 Moreover, in vitro , studies revealed outstanding inhibitory efficacy of PN against the growth of breast cancer, 31 cervical, 32 lung cancers, 33 HL-60 and K562 leukaemia cells. 34 Moreover, PN also exhibited significant free radical quenching and anti-inflammation actions in silver nanoparticle-treated fibroblasts. 35 More recently, PN (30 and 60 mg/kg of PN) showed significant hepatoprotective potentials in rats, which were linked to its positive modulation of antioxidant, immunohistochemical and inflammatory pathways.…”

Section: Introductionmentioning

confidence: 99%

Pinostrobin attenuates azoxymethane-induced colorectal cytotoxicity in rats through augmentation of apoptotic Bax/Bcl-2 proteins and antioxidants

Ali Abed Wahab,

Ain Salehen,

Abdulla

et al. 2023

SAGE Open Medicine

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Objectives: Pinostrobin (5-hydroxy-7-methoxyflavanone; PN) is a natural active ingredient with numerous biological activities extensively utilized in tumour chemotherapy. The present study investigates the chemo-preventive potentials of PN on azoxymethane-mediated colonic aberrant crypt foci in rats. Methods: Sprague Dawley rats clustered into five groups, normal control (A) and cancer controls were subcutaneously injected with normal saline and 15 mg/kg azoxymethane, respectively, and nourished on 10% tween 20 and fed on 10% tween 20; reference control (C), injected with 15 mg/kg azoxymethane and injected (intraperitoneal) with 35 mg/kg 5-fluorouracil (5-FU); D and E rat groups received a subcutaneous injection of 15 mg/kg azoxymethane and nourished on 30 and 60 mg/kg of PN, respectively. Results: The acute toxicity trial showed a lack of any abnormal signs or mortality in rats ingested with 250 and 500 mg/kg of PN. The gross morphology of colon tissues revealed significantly lower total colonic aberrant crypt foci incidence in PN-treated rats than that of cancer controls. Histological examination of colon tissues showed increased aberrant crypt foci availability with bizarrely elongated nuclei, stratified cells and higher depletion of the submucosal glands in cancer controls. PN treatment caused positive modulation of apoptotic (Bax and Bcl-2) proteins and inflammatory cytokines (TNF-α, IL-6 and IL-10). Moreover, rats fed on PN had significantly higher antioxidants (superoxide dismutase) and lower malondialdehyde concentrations in their colon tissue homogenates. Conclusion: The chemoprotective efficiency of PN against azoxymethane-induced aberrant crypt foci is shown by lower aberrant crypt foci values and higher aberrant crypt foci inhibition percentage, possibly through augmentation of genes responsible for apoptotic cascade and inflammations originating from azoxymethane oxidative stress insults.

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