4-Nerolidylcatechol: apoptosis by mitochondrial mechanisms with reduction in cyclin D1 at G0/G1 stage of the chronic myelogenous K562 cell line

Benfica, Polyana Lopes; Ávila, Renato Ivan de; Rodrigues, Bruna dos Santos; Cortez, Alane Pereira; Batista, Aline Carvalho; Gaeti, Marilisa Pedroso Nogueira; Lima, Eliana Martins; Rezende, Kênnia Rocha; Valadares, Marize Campos

doi:10.1080/13880209.2017.1311351

Cited by 12 publications

(7 citation statements)

References 61 publications

(67 reference statements)

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“…The cells in the sub-G1 phase of the cell cycle are in the state of the progression of the apoptosis. 17 The percentage of the INS-1 cells in sub-G1 phase increased by more than 30% in the HGP culture condition as compared with the control group. Melatonin treatment significantly reduced the percentage of the INS-1 cells in the sub-G1 phase in the HGP culture condition.…”

Section: The Effects Of the Melatonin On The Cell Cyclementioning

confidence: 89%

Melatonin protects INS-1 pancreatic β-cells from apoptosis and senescence induced by glucotoxicity and glucolipotoxicity

Lee

Jung

Kwon

et al. 2020

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Introduction: Melatonin is a hormone known as having very strong anti-oxidant property. Senescence is a biological state characterized by the loss of cell replication and the changes consisting of a pro-inflammatory phenotype, leading to Senescence Associated Secretory Phenotype (SASP) which is now regarded as one of the fundamental processes of many degenerative diseases. Increased cell division count induces cell senescence via DNA damage in response to elevated Reactive Oxygen Species (ROS). We wanted to test whether melatonin could reduce apoptosis and stress induced premature pancreatic β-cell senescence induced by glucotoxicity and glucolipotoxicity. Materials and method: Cultured rodent pancreatic β-cell line (INS-1 cell) was used. Glucotoxicity (HG: hyperglycemia) and glucolipotoxicity (HGP: hyperglycemia with palmitate) were induced by hyperglycemia and the addition of palmitate. The degrees of the senescence were measured by SAβ-Gal and P16 lnk4A staining along with the changes of cell viabilities, cell cycle-related protein and gene expressions, endogenous anti-oxidant defense enzymes, and Glucose Stimulated Insulin Secretion (GSIS), before and after melatonin treatment. Results: Cultured INS-1 cells in HG and HGP conditions revealed accelerated senescence, increased apoptosis, cell cycle arrest, compromised endogenous anti-oxidant defense, and impaired glucosestimulated insulin secretion. Melatonin decreased apoptosis and expressions of proteins related to senescence, increase the endogenous anti-oxidant defense, and improved glucose-stimulated insulin secretion. Conclusion:Melatonin protected pancreatic β-cell from apoptosis, decreased expressions of the markers related to the accelerated senescence, and improved the biological deteriorations induced by glucotoxicity and glucolipotoxicity.

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Section: The Effects Of the Melatonin On The Cell Cyclementioning

confidence: 89%

Melatonin protects INS-1 pancreatic β-cells from apoptosis and senescence induced by glucotoxicity and glucolipotoxicity

Lee

Jung

Kwon

et al. 2020

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“…Cells accumulated in the sub G0/G1 phase are classified as apoptotic cells with DNA fragmentation and mitochondrial dysfunction (64)(65)(66). We further investigated whether the attenuation of apoptosis was related to suppression of caspase activity and DNA damage, as well as the mitochondrial dysfunction.…”

Section: Il-4 and Il-21 Rescued Ramos Cells Through Differential Mech...mentioning

confidence: 99%

Interleukins 4 and 21 Protect Anti-IgM Induced Cell Death in Ramos B Cells: Implication for Autoimmune Diseases

Hui¹,

Wu²,

Leung³

2022

Front. Immunol.

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Interleukins 4 (IL-4) and 21 (IL-21) belong to the common gamma chain cytokine family which are highly involved in the progression of autoimmune diseases. While IL-4 is well known to be involved in the suppression of apoptosis of autoreactive B cells, the role played by IL-21 remains unclear. In the current study, we activated the human Burkitt’s lymphoma Ramos B cells with anti-IgM to mimic B cell hyperactivation observed in patients of autoimmune diseases. Consistent with other reported findings, anti-IgM led to the downregulation of proteins involved in B cell survival and proliferation, as well as the activation of caspase 3 activity and DNA damage, resulting in apoptotic cell death after 48-hour treatment. Although both IL-4 and IL-21 reversed anti-IgM-induced apoptosis and cell cycle arrest, they did so via different mechanisms: while IL-4 could directly suppress anti-IgM-induced caspase 3 activation and marker indicative of DNA damage, IL-21 could induce B cell proliferation in the presence of anti-IgM. Importantly, IL-21 also suppressed activation induced cell death in human primary B cells. Pre-treatment with clinically validated JAK inhibitors completely reversed the effects of IL-4 and IL-21 to rescue anti-IgM induced cell death and DNA damage. The results indicate the underlying mechanisms of how IL-4 and IL-21 differentially promote survival of hyperactivated B cells and provide hints to treat autoimmune diseases.

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“…Recently, it was demonstrated that 4-NRC-induced apoptosis in human chronic myeloid leukemia K562 cells by mitochondrial-dependent pathways (Benfica et al 2015).…”

Section: Effectsmentioning

confidence: 99%

4-Nerolidylcatechol analogues as promising anticancer agents

Cortez

Ávila

Cunha

et al. 2015

European Journal of Pharmacology

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4-Nerolidylcatechol (1) is an isolated compound from Pothomorphe umbellata L. (Piperaceae) with promising antitumor cells properties. However it presents lability under light and room temperatures. Many efforts have been directed towards discovering anticancer agents endowed with cytotoxic activities. Here, we evaluated cytotoxic effects of 4-NRC analogues (LQFMs 2-6) and the cell death pathways induced by these compounds in multidrug-resistant K562 cells. Compounds (2-6) exhibited cytotoxic activities in a concentration-dependent manner against leukaemic cells, specially the compounds (3) and (5). Additionally, compounds (1), (3) and (5) promoted marked alterations on the cell morphology, including nuclear changes as demonstrated by Hoescht 33342 staining. Moreover, these compounds promoted apoptosis induction in K562 cells by phosphatidylserine exposure, increase of sub-G1 cells and modulation of the caspases-3/7, -8 and -9 activation. In addition, the pancaspase inhibitor z-VAD-fmk partially reduced the apoptosis induced by the compounds (1) and (5)-induced, suggesting caspase-dependent and caspase-independent cell death pathways. Compounds (1) and (5) also modified the cell cycle progression by G0/G1 and S arrest, respectively. Furthermore, compounds (1), (3) and (5) promoted mitochondrial dysfunction associated to accumulation of cytosolic cytochrome c and modulated the NF-ĸB activation. In addition, unlike their analogues, 4-NRC (1) also promoted a significant cyclin D1 inhibition. Together, these data suggest that the mechanism of cell death of 4-NRC and its analogues (3) and (5) occurs by apoptosis through mitochondrial mechanisms. Considering that LQFMs are biocompatible synthetic analogues produced by molecular simplification of (1) without the chiral centre, which is associated with the instability found in compound (1), we suggest that these compounds are promising candidates for further pre-clinical studies.

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4-Nerolidylcatechol: apoptosis by mitochondrial mechanisms with reduction in cyclin D1 at G0/G1 stage of the chronic myelogenous K562 cell line

Cited by 12 publications

References 61 publications

Melatonin protects INS-1 pancreatic β-cells from apoptosis and senescence induced by glucotoxicity and glucolipotoxicity

Melatonin protects INS-1 pancreatic β-cells from apoptosis and senescence induced by glucotoxicity and glucolipotoxicity

Interleukins 4 and 21 Protect Anti-IgM Induced Cell Death in Ramos B Cells: Implication for Autoimmune Diseases

4-Nerolidylcatechol analogues as promising anticancer agents

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