Ceramide induces cell cycle arrest and upregulates p27kip in nasopharyngeal carcinoma cells

Zhu, Xiao Feng; Liu, Zong Chao; Xie, Bingteng; Feng, Gong Kan; Zeng, Yi Xin

doi:10.1016/s0304-3835(03)00050-8

Cited by 28 publications

(16 citation statements)

References 21 publications

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“…Together, these results indicate that a G1 arrest of the cell cycle following inhibition of PI3K can be attributed to a significant increase in p27 Kip1 protein expression in cervical cancer. A similar study has shown that treatment with ceramide up-regulates p27 Kip1 expression, leading to cell cycle arrest and induction of apoptosis [49]. We found that a combined application of MG132 and LY294002 resulted in a significant increase in AnnexinV positive cells and the expression of cleaved PARP.…”

Section: Mg132 Enhances the Growth Inhibitory Effect Of Ly294002 And supporting

confidence: 77%

PI3K/AKT pathway-mediated regulation of p27Kip1 is associated with cell cycle arrest and apoptosis in cervical cancer

et al. 2015

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Section: Mg132 Enhances the Growth Inhibitory Effect Of Ly294002 And supporting

confidence: 77%

PI3K/AKT pathway-mediated regulation of p27Kip1 is associated with cell cycle arrest and apoptosis in cervical cancer

et al. 2015

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“…4 That said, in support of our observations, a partial ceramide-mediated G 2 /M arrest albeit in the presence of a substantial G 0 /G 1 arrest was reported in W138 human diploid fibroblasts 4 and NIH-3T3 cells. 39 The observed upregulation in p21 Cip1/Waf1 expression described here in the absence of Rb dephosphorylation or the stabilization of p27 Kip1 , which has also been associated with ceramidemediated G 0 /G 1 -arrest, 38 may in part account for the selective arrest of RD cells in the G 2 phase of the cell cycle rather than G 0 /G 1 . Collectively, these data imply that the ceramidemediated modulation of cell cycle progression is cell type specific, and is further dictated to by the basal activity and expression of other cell cycle regulators.…”

Section: Discussionmentioning

confidence: 78%

Ceramide-induced G2 arrest in rhabdomyosarcoma (RMS) cells requires p21Cip1/Waf1 induction and is prevented by MDM2 overexpression

et al. 2007

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The sphingoplipid ceramide is responsible for a diverse range of biochemical and cellular responses including a putative role in modulating cell cycle progression. Herein, we describe that an accumulation of ceramide, achieved through the exogenous application of C 6 -ceramide or exposure to sphingomyelinase, induces a G 2 arrest in Rhabdomyosarcoma (RMS) cell lines. Utilizing the RMS cell line RD, we show that this G 2 arrest required the rapid induction of p21 Cip1/Waf1 independent of DNA damage. This was followed at later time points (48 h) by the commitment to apoptosis. Apoptosis was prevented by Bcl-2 overexpression, but permitted the maintenance of elevated p21 Cip1/Waf1 protein expression and the stabilization of the G 2 arrest response. Inhibition of p21 Cip1/Waf1 protein synthesis with cyclohexamide (CHX) or silencing of p21 Cip1/Waf1 with siRNA, prevented ceramide-mediated G 2 arrest and the late induction of apoptosis. Further, adopting the recent discovery that murine double minute 2 (MDM2) controls p21 Cip1/Waf1 expression by presenting this CDK inhibitor to the proteasome for degradation, RD cells overexpressing MDM2 abrogated ceramide-mediated p21 Cip1/Waf1 induction, G 2 arrest and the late ensuing apoptosis. Collectively, these data further support the notion that ceramide accumulation can modulate cell cycle progression. Additionally, these observations highlight MDM2 expression and proteasomal activity as key determinants of the cellular response to ceramide accumulation.

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“…DMSO (100 l) was added to each well to dissolve the dark blue crystal, and the plate was shaken gently for 5 min. The optical density values were read with a test wavelength of 570 nm and a reference wavelength of 650 nm (Zhu et al, 2003).…”

Section: Methodsmentioning

confidence: 99%

Blockade of Vascular Endothelial Growth Factor Receptor Signal Pathway and Antitumor Activity of ON-III (2′,4′-Dihydroxy-6′-methoxy-3′,5′-dimethylchalcone), a Component from Chinese Herbal Medicine

Zhu

Xie²,

Zhou³

et al. 2005

Mol Pharmacol

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Antiangiogenesis is a promising strategy of cancer treatment. Vascular endothelial growth factor receptor [fetal liver kinase/ kinase-inserting domain-containing receptor (KDR)] is a tyrosine kinase receptor and has been strongly implicated in tumor angiogenesis. In this study, we report that 2Ј,4Ј-dihydroxy-6Ј-methoxy-3Ј,5Ј-dimethylchalcone (ON-III), extracted from the dried flower Cleistocalyx operculatus, used in traditional Chinese medicine, reversibly inhibited KDR tyrosine kinase phosphorylation, but epidermal growth factor receptor tyrosine kinase phosphorylation was unaffected under the same concentrations of ON-III. ON-III also inhibited mitogenactivated protein kinase (MAPK) and AKT activation of KDR signal transduction in downstream molecules without reduced total MAPK and AKT. The results in vitro showed that ON-III inhibited growth of human vascular endothelial HDMEC cells in the presence of VEGF preferentially, compared with epidermal growth factor. Systemic administration of ON-III at nontoxic doses in nude mice resulted in inhibition of subcutaneous tumor growth of human hepatocarcinoma Bel7402 and lung cancer GLC-82 xenografts. The tumor vessel density decreased, as determined by immunohistochemical staining, for CD31 after ON-III treatment. These results indicated that ON-III inhibited KDR tyrosine kinase, shut down KDR-mediated signal transduction, and inhibited tumor growth of human xenografts in vivo.

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Ceramide induces cell cycle arrest and upregulates p27kip in nasopharyngeal carcinoma cells

Cited by 28 publications

References 21 publications

PI3K/AKT pathway-mediated regulation of p27Kip1 is associated with cell cycle arrest and apoptosis in cervical cancer

PI3K/AKT pathway-mediated regulation of p27Kip1 is associated with cell cycle arrest and apoptosis in cervical cancer

Ceramide-induced G2 arrest in rhabdomyosarcoma (RMS) cells requires p21Cip1/Waf1 induction and is prevented by MDM2 overexpression

Blockade of Vascular Endothelial Growth Factor Receptor Signal Pathway and Antitumor Activity of ON-III (2′,4′-Dihydroxy-6′-methoxy-3′,5′-dimethylchalcone), a Component from Chinese Herbal Medicine

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