Ceramide Produces Apoptosis Through Induction of p27<sup>kip1</sup>by Protein Phosphatase 2A-dependent Akt Dephosphorylation in PC-3 Prostate Cancer Cells

Kim, Sang Woo; Kim, Hae Jong; Chun, Young Jin; Kim, Mie Young

doi:10.1080/15287394.2010.511553

Cited by 45 publications

(32 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Akt can regulate the cell cycle by enhancing the transcription of cell cycle regulators and modulating their stability directly or indirectly through phosphorylation on specific sites (16,(27)(28)(29). Consistent with the previous study, we observed that ASA induced HepG2 cell accumulation in the G0/G1 phase.…”

Section: Discussionsupporting

confidence: 82%

Aspirin reduces the apoptotic effect of etoposide via Akt activation and up-regulation of p21cip

Feng

Lü²,

Xu³

et al. 2011

Int J Mol Med

View full text Add to dashboard Cite

Abstract. Previous studies on the apoptotic effect of aspirin mainly focus on colorectal cancer and breast carcinoma. Few studies have been designed to explore the effect of aspirin on hepatocellular carcinoma. In the present study, we observed that aspirin caused G0/G1 phase cell cycle arrest and reduced etoposide induced caspase-3 activation in hepatocellular carcinoma G2 (HepG2) cells. Further investigation demonstrated that aspirin notably enhanced the activity of Akt and ERK1/2. Blocking the activation of Akt by the PI3-K-selective inhibitor wortmannin abrogated the anti-apoptotic effect of aspirin while the MEK inhibitor U0126 did not. p21 cip , an important substrate of Akt, is involved in the regulation of cell cycle arrest and apoptosis. Our data showed that the protein expression and ser146 phosphorylation levels of p21 cip were significantly increased after treatment with aspirin, whereas p53 or p27 showed no change. The increase of p21 cip protein levels was also scavenged by wortmannin but not by U0126. Moreover, reduction of caspase-3 activity induced by aspirin was attenuated by silencing p21 cip expression. These results indicated that the anti-apoptotic effect of aspirin was dependent on activation of Akt which inhibited cell apoptosis by up-regulating p21 cip and blocking caspase-3 activation. These findings could have clinical relevance in anticancer therapy and aspirin co-treatment of human malignancies.

show abstract

Section: Discussionsupporting

confidence: 82%

Aspirin reduces the apoptotic effect of etoposide via Akt activation and up-regulation of p21cip

Feng

Lü²,

Xu³

et al. 2011

Int J Mol Med

View full text Add to dashboard Cite

show abstract

“…Use of ceramide to treat PC-3 human prostate cancer cells revealed that ceramide-activated PP2A dephosphorylates phospho-Akt (25). In this study, we found that OA reversed YBBEs-mediated downregulation of p-PI3K, p-Akt and p-MDM2, suggesting that targeting PP2A may be a feasible way to affect the pivotal stage.…”

Section: Discussionmentioning

confidence: 51%

Zanthoxylum avicennae extracts inhibit cell proliferation through protein phosphatase 2A activation in HA22T human hepatocellular carcinoma cells in vitro and in vivo

et al. 2012

View full text Add to dashboard Cite

Abstract. Hepatocellular carcinoma is a common type of cancer that is usually associated with poor prognosis. In this study, we examined the in vitro and in vivo mechanisms of the traditional Vietnamese herb Zanthoxylum avicennae on the inhibition of HA22T human hepatocellular carcinoma cell proliferation. HA22T cells were treated with different concentrations of Zanthoxylum avicennae extracts (YBBEs) and analyzed with the MTT assay, western blot analysis, flow cytometry, siRNA transfection assays and co-immunoprecipitation assay. Additionally, the HA22T-implanted xenograft nude mouse model was applied to confirm the cellular effects. YBBEs showed a strong inhibition of HA22T cell viability in a dose-dependent manner and significantly reduced cell proliferation-related proteins as well as induced cell cycle arrest in the G2/M phase. Protein phosphatase 2A (PP2A) siRNA or okadaic acid totally blocked YBBE-mediated cell proliferation inhibition. In addition, an HA22T-implanted nude mouse model further confirmed that YBBEs inhibit HA22T tumor cell growth and downregulate the survival and cell cycle regulating proteins, as well as activate the PP2A protein. Our findings indicate that the inhibition of HA22T cell proliferation by YBBEs is mediated through PP2A activation.

show abstract

“…For instance, de novo ceramide generation was found to be important for triggering apoptosis specifically in melanoma cells as evidenced by the lack of apoptosis when serine palmitoyltransferase activity is blocked [42]. However in prostate cancer cancer cell lines, ceramide-mediated apoptosis appeared to be driven by Akt dephosphorylation through protein phosphatase 2A activity [43]. Similarly, in another study, ceramide analogs were shown to induce apoptosis by affecting mitochondria along with the concomitant dephosphorylation of Akt [44].…”

Section: Cellular Roles Of Bioactive Sphingolipidsmentioning

confidence: 97%

Bioactive Sphingolipids in Response to Chemotherapy: A Scope on Leukemias

Ekiz

Baran²

2011

ACAMC

View full text Add to dashboard Cite

Sphingolipids are major constituents of the cells with emerging roles in the regulation of cellular processes. Deregulation of sphingolipid metabolism is reflected as various pathophysiological conditions including metabolic disorders and several forms of cancer. Ceramides, ceramide-1-phosphate (C1P), glucosyl ceramide (GluCer), sphingosine and sphingosine-1-phosphate (S1P) are among the bioactive sphingolipid species that have important roles in the regulation of cell death, survival and chemotherapeutic resistance. Some of those species are known to accumulate in the cells upon chemotherapy while some others are known to exhibit an opposite pattern. Even though the length of fatty acid chain has a deterministic effect, in general, upregulation of ceramides and sphingosine is known to induce apoptosis. However, S1P, C1P and GluCer are proliferative for cells and they are involved in the development of chemoresistance. Therefore, sphingolipid metabolism appears as a good target for the development of novel therapeutics or supportive interventions to increase the effectiveness of the chemotherapeutic drugs currently in hand. Some approaches involve manipulation of the synthesis pathways yielding the increased production of apoptotic sphingolipids while the proliferative ones are suppressed. Some others are trying to take advantage of cytotoxic sphingolipids like short chain ceramide analogs by directly delivering them to the malignant cells as a distinct chemotherapeutic intervention. Numerous studies in the literature show the feasibility of those approaches especially in acute and chronic leukemias. This review compiles the current knowledge about sphingolipids and their roles in chemotherapeutic response with the particular attention to leukemias.

show abstract

Ceramide Produces Apoptosis Through Induction of p27^kip1by Protein Phosphatase 2A-dependent Akt Dephosphorylation in PC-3 Prostate Cancer Cells

Cited by 45 publications

References 39 publications

Aspirin reduces the apoptotic effect of etoposide via Akt activation and up-regulation of p21cip

Aspirin reduces the apoptotic effect of etoposide via Akt activation and up-regulation of p21cip

Zanthoxylum avicennae extracts inhibit cell proliferation through protein phosphatase 2A activation in HA22T human hepatocellular carcinoma cells in vitro and in vivo

Bioactive Sphingolipids in Response to Chemotherapy: A Scope on Leukemias

Contact Info

Product

Resources

About

Ceramide Produces Apoptosis Through Induction of p27kip1by Protein Phosphatase 2A-dependent Akt Dephosphorylation in PC-3 Prostate Cancer Cells

Cited by 45 publications

References 39 publications

Aspirin reduces the apoptotic effect of etoposide via Akt activation and up-regulation of p21cip

Aspirin reduces the apoptotic effect of etoposide via Akt activation and up-regulation of p21cip

Zanthoxylum avicennae extracts inhibit cell proliferation through protein phosphatase 2A activation in HA22T human hepatocellular carcinoma cells in vitro and in vivo

Bioactive Sphingolipids in Response to Chemotherapy: A Scope on Leukemias

Contact Info

Product

Resources

About

Ceramide Produces Apoptosis Through Induction of p27^kip1by Protein Phosphatase 2A-dependent Akt Dephosphorylation in PC-3 Prostate Cancer Cells