Fusarochromanone Induces G1 Cell Cycle Arrest and Apoptosis in COS7 and HEK293 Cells

Gu, Ying; Chen, Xin; Shang, Chaowei; Singh, Karnika; Barzegar, Mansoureh; Mahdavian, Elahe; Salvatore, Brian A.; Jiang, Shanxiang; Huang, Shile

doi:10.1371/journal.pone.0112641

Cited by 7 publications

(8 citation statements)

References 35 publications

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“…In addition, apoptosis is a complex process that is tightly regulated by a balance of pro‐apoptotic and anti‐apoptotic proteins (Gu et al, ). Apaf‐1, one of pro‐apoptotic proteins, mediates the cytochrome c‐dependent autocatalytic activation of pro‐caspase‐9, leading to the activation of caspase‐3 and apoptosis (Saleh et al, ).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of cell growth and induction of inflammation by endosulfan in HUVEC-C cells

Guo

et al. 2015

Environ. Toxicol.

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Endosulfan is one of the organochlorine pesticides. It has been associated with a wide range of adverse health effects. However, it is unknown whether endosulfan causes endothelial dysfunction. In the present study, we investigated the effects of endosulfan on human vascular endothelial cells. We exposed human umbilical vein endothelial cells (HUVEC-C) to varying concentrations of endosulfan for 48 h. The results showed that endosulfan lowered cell viability and inhibited cell proliferation in a dose-dependent manner. Flow cytometric analysis showed that endosulfan at 60 μM induced G1 cell cycle arrest, a response attributed to down-regulation of CDK6 and pRb dephosphorylation. We observed that endosulfan at 40 and 60 μM induced a considerable percentage of cells to undergo apoptosis, as detected by Annexin-V binding assays. Endosulfan reduced mitochondrial transmembrane potential, leading to the release of cytochrome c into the cytoplasm; meanwhile, endosulfan also inhibited the mRNA expression level of survivin, which resulted in the activation of caspase-3. These results indicated that the intrinsic mitochondria-mediated pathway was involved in apoptotic process. Exposure to endosulfan increased the secretion and mRNA expression levels of inflammation factors interleukin (IL)-6 and IL-8, suggesting that endosulfan could cause inflammation. Overall, these findings suggested that endosulfan is toxic to HUVEC-C cells, resulting in endothelial dysfunction. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1785-1795, 2016.

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Section: Discussionmentioning

confidence: 99%

Inhibition of cell growth and induction of inflammation by endosulfan in HUVEC-C cells

Guo

et al. 2015

Environ. Toxicol.

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“…The present study demonstrated that ADRP knockdown inhibited PDGF-induced growth and proliferation of VSMCs, and that this anti-proliferative effect was associated with increased cell cycle arrest at G1 phase. Cell proliferation is controlled by cell cycle progression, which is regulated by the complexes of cyclins and cyclin-dependent kinases ( 31 ). PCNA is a cell cycle protein in the nucleus and functions in DNA synthesis ( 32 ).…”

Section: Discussionmentioning

confidence: 99%

Adipose differentiation-related protein knockdown inhibits vascular smooth muscle cell proliferation and migration and attenuates neointima formation

Zhao

Han

Hong

et al. 2017

Molecular Medicine Reports

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Vascular smooth muscle cells (VSMCs) have an important role in atherosclerosis development. Evidence has demonstrated that adipose differentiation-related protein (ADRP) is associated with foam cell formation and atherosclerosis progression. However, to the best of our knowledge, no previous studies have investigated the role of ADRP knockdown in platelet-derived growth factor (PDGF)-stimulated proliferation and migration of VSMCs in vitro. Furthermore, the effect of ADRP knockdown on neointima formation in vivo remains unclear. In the present study, primary human aortic VSMCs were incubated with PDGF following ADRP small interfering (si)RNA transfection. Cell viability, migration and cell cycle distribution were analyzed by MTT, wound healing and Transwell assays and flow cytometry, respectively. Extracellular signal-regulated kinase (ERK), phosphorylated (p)-ERK, Akt, p-Akt, proliferating cell nuclear antigen (PCNA), matrix metalloproteinase (MMP)-2 and MMP-9 protein levels were determined by western blotting. Apolipoprotein E−/− mice fed an atherogenic diet were injected with siADRP or control siRNA twice a week. After 3 weeks of therapy, aortas were excised and ADRP mRNA and protein expression was determined. Neointima formation was assessed by hematoxylin and eosin staining. The results of the current study demonstrated that ADRP knockdown significantly inhibited PDGF-induced increases in VSMC viability, caused G1 phase cell cycle arrest and decreased PCNA expression. Knockdown of ADRP inhibited PDGF-induced migration of VSMCs by reducing MMP protein expression and activity. In addition, the present study also demonstrated that ADRP knockdown inhibited ERK and Akt signaling pathways in response to PDGF. Furthermore, siADRP administration suppressed neointima formation in the mouse model. The results of the present study indicate that ADRP may be a potential target for the treatment of atherosclerosis.

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“…FC101 is a toxic fungal metabolite mainly produced by F. equiseti [ 12 ], which has been observed frequently in human food and animal feedstuffs [ 1 – 4 , 43 ]. Although it has been shown that FC101 induces cell death [ 11 – 16 ], the underlying molecular mechanism is still poorly understood. Here we demonstrate that FC101 induces ROS, causing the activation of the stress kinase JNK cascade, leading to cell death.…”

Section: Discussionmentioning

confidence: 99%

“…Cell viability was evaluated using CellTiter 96 ® AQ ueous One Solution Cell Proliferation Assay kit (Promega), as described [ 16 ]. Briefly, cells suspended in the growth medium were seeded in a 96-well plate at a density of 1 × 10 4 cells/well (in triplicates) and were grown overnight at 37°C in a humidified incubator with 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

“…Later, FC101 was also suspected to be associated with etiology of Kashin-Beck disease (a chronic and endemic osteochondropathy) in children in northeastern and southwestern China, as well as in southeastern Siberia and northern Korea [ 9 , 10 ]. Furthermore, FC101 has recently been found to inhibit cell proliferation and differentiation as well as induce cell death in lymphocytes, osteoblasts, melanoma cells, breast cancer cells, glioblastoma cells, normal cardiac fibroblasts and kidney cells [ 11 – 16 ]. Despite these findings, how FC101 causes cytotoxicity is not well understood.…”

Section: Introductionmentioning

confidence: 99%

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Fusarochromanone-induced reactive oxygen species results in activation of JNK cascade and cell death by inhibiting protein phosphatases 2A and 5

Barzegar

Chen

et al. 2015

Oncotarget

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Recent studies have shown that fusarochromanone (FC101), a mycotoxin, is cytotoxic in a variety of cell lines. However, the molecular mechanism underlying its cytotoxicity remains elusive. Here we found that FC101 induced cell death in COS7 and HEK293 cells in part by activating JNK pathway. This is evidenced by the findings that inhibition of JNK with SP600125 or expression of dominant negative c-Jun partially prevented FC101-induced cell death. Furthermore, we observed that FC101-activated JNK pathway was attributed to induction of reactive oxygen species (ROS). Pretreatment with N-acetyl-L-cysteine (NAC), a ROS scavenger and antioxidant, suppressed FC101-induced activation of JNK and cell death. Moreover, we noticed that FC101 inhibited the serine/threonine protein phosphatases 2A (PP2A) and 5 (PP5) in the cells, which was abrogated by NAC. Overexpression of PP2A or PP5 partially prevented FC101-induced activation of JNK and cell death. The results indicate that FC101-induced ROS inhibits PP2A and PP5, leading to activation of JNK pathway and consequently resulting in cell death.

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Fusarochromanone Induces G1 Cell Cycle Arrest and Apoptosis in COS7 and HEK293 Cells

Cited by 7 publications

References 35 publications

Inhibition of cell growth and induction of inflammation by endosulfan in HUVEC-C cells

Inhibition of cell growth and induction of inflammation by endosulfan in HUVEC-C cells

Adipose differentiation-related protein knockdown inhibits vascular smooth muscle cell proliferation and migration and attenuates neointima formation

Fusarochromanone-induced reactive oxygen species results in activation of JNK cascade and cell death by inhibiting protein phosphatases 2A and 5

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