Deoxypodophyllotoxin induces G2/M cell cycle arrest and apoptosis in HeLa cells

Shin, Soon Young; Yong, Yeonjoong; Kim, Chang Gun; Lee, Young Han; Lim, Yoongho

doi:10.1016/j.canlet.2009.06.019

Cited by 86 publications

(65 citation statements)

References 44 publications

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“…A chemical analogue of podophyllotoxin called deoxypodophyllotoxin is known to activate CASP7 as part of its apoptotic mechanism. 22 These results support a detectable cellular transcriptional signature resulting from the chemical modulation of tubulin. Multiple compounds that were polyphenolic flavonoid natural-product scaffolds, such as resveratrol, quercetin, and luteolin, were correctly predicted to have CYP1B1 as a target.…”

Section: Compound-target Prediction Examplesmentioning

confidence: 52%

Causal Network Models for Predicting Compound Targets and Driving Pathways in Cancer

et al. 2014

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Gene-expression data are often used to infer pathways regulating transcriptional responses. For example, differentially expressed genes (DEGs) induced by compound treatment can help characterize hits from phenotypic screens, either by correlation with known drug signatures or by pathway enrichment. Pathway enrichment is, however, typically computed with DEGs rather than "upstream" nodes that are potentially causal of "downstream" changes. Here, we present graphbased models to predict causal targets from compound-microarray data. We test several approaches to traversing network topology, and show that a consensus minimum-rank score (SigNet) beat individual methods and could highly rank compound targets among all network nodes. In addition, larger, less canonical networks outperformed linear canonical interactions. Importantly, pathway enrichment using causal nodes rather than DEGs recovers relevant pathways more often. To further validate our approach, we used integrated data sets from the Cancer Genome Atlas to identify driving pathways in triple-negative breast cancer. Critical pathways were uncovered, including the epidermal growth factor receptor 2-phosphatidylinositide 3-kinase-AKT-MAPK growth pathway and ATR-p53-BRCA DNA damage pathway, in addition to unexpected pathways, such as TGF-WNT cytoskeleton remodeling, IL12-induced interferon gamma production, and TNFR-IAP (inhibitor of apoptosis) apoptosis; the latter was validated by pooled small hairpin RNA profiling in cancer cells. Overall, our approach can bridge transcriptional profiles to compound targets and driving pathways in cancer.

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Section: Compound-target Prediction Examplesmentioning

confidence: 52%

Causal Network Models for Predicting Compound Targets and Driving Pathways in Cancer

et al. 2014

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“…In the present study, DPPT significantly inhibited cell proliferation and cell apoptosis of DU-145 cells in a dose-and time-dependent manner. Several studies indicated that DPPT significantly induced cell apoptosis of HeLa cells (14), breast cancer cells (15) and non-small cell lung cancer cells (16). These results indicated that DPPT may be considered as a drug to target PCa.…”

Section: Discussionmentioning

confidence: 93%

“…The present results revealed that treatment with DPPT significantly reduced p-Akt protein expression, and increased p53 and Bax protein expression in DU-145 cells. Shin et al (14) suggested that DPPT induces G2/M cell-cycle arrest through inhibition of Akt and upregulation of the p53 and Bax signaling pathway in HeLa cells. Sang et al (20) demonstrated that DPPT induces cell apoptosis of non-small cell lung cancer A549 cells through p53/cell division cycle 2/Bax signaling.…”

Section: Discussionmentioning

confidence: 99%

“…In the present study, treatment with DPPT significantly promoted PTEN protein expression in DU-145 cells. Shin et al (14) suggested that DPPT induces G2/M cell-cycle arrest through inhibition of Akt and activation of the PTEN signaling pathway in HeLa cells. Consequently, the present results provide the initial evidence that DPPT induces cell apoptosis via the PTEN signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

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Anticancer effect of deoxypodophyllotoxin induces apoptosis of human prostate cancer cells

Zhou

et al. 2016

Oncology Letters

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Abstract. Deoxypodophyllotoxin (DPPT) is extracted and separated from citrus-related plants, including Podophyllum (P.) peltatum, P. pleianthum, P. emodi (also called P. hexandrum) and Diphylleia grayi. DPPT has significant antitumor and antiviral activity. However, due to its strong toxicity and side effects, its use is limited in practical applications. The in vitro antitumor efficacy of DPPT on human prostate cancer (PCa) cells remains to be determined. The present study investigated the anticancer effect of DPPT on human PCa cells and its potential mechanism. The data revealed that DPPT markedly reduced cell proliferation and activated the caspase-3 expression level by an increase in apoptotic cell death in DU-145 cells. In addition, treatment with DPPT markedly downregulated the levels of phosphorylated Akt and activated the p53/B-cell lymphoma 2 associated X protein (Bax)/phosphatase and tensin homolog (PTEN) signaling pathway in DU-145 cells, suggesting that caspase-mediated pathways were involved in DPPT-induced apoptosis. The present study suggested the role of DPPT as a novel chemotherapeutic drug for human PCa, which may function through the Akt/p53/Bax/PTEN signaling pathway.

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“…It has been reported that p53 could induce the expression of bax protein. 28) Upregulation of p53 and bax protein were observed in Deoxypodophyllotoxin-induced apoptosis in HeLa cells, 44) and in 6-hydroxydopamine-induced apoptosis in PC12 cells. 45) The results indicate that the accumulation of bax protein is possibly induced by p53 which has been activated in genipin-treated HeLa cells, and the accumulation of bax protein induces cell apoptotic death eventually.…”

Section: Fig 8 Effect Of Genipin On Activation Of Bax Protein In Hementioning

confidence: 99%

Genipin Induced Apoptosis Associated with Activation of the c-Jun NH2-Terminal Kinase and p53 Protein in HeLa Cells

Houli

Qian

et al. 2010

Biological & Pharmaceutical Bulletin

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Deoxypodophyllotoxin induces G2/M cell cycle arrest and apoptosis in HeLa cells

Cited by 86 publications

References 44 publications

Causal Network Models for Predicting Compound Targets and Driving Pathways in Cancer

Causal Network Models for Predicting Compound Targets and Driving Pathways in Cancer

Anticancer effect of deoxypodophyllotoxin induces apoptosis of human prostate cancer cells

Genipin Induced Apoptosis Associated with Activation of the c-Jun NH2-Terminal Kinase and p53 Protein in HeLa Cells

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