Different levels of p53 induced either apoptosis or cell cycle arrest in a doxycycline-regulated hepatocellular carcinoma cell line in vitro

Lai, Paul B.S.; Chi, Tianyi; Chen, George G.

doi:10.1007/s10495-006-0571-1

Cited by 68 publications

(50 citation statements)

References 21 publications

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“…It is well known that p53 mediates cell cycle arrest and apoptosis in tumour cells (Lai et al, 2007). The results from our study also showed that p53 mediates cell cycle arrest and apoptosis of macrophages upon L. interrogans infection.…”

Section: Discussionsupporting

confidence: 83%

p53 signalling controls cell cycle arrest and caspase-independent apoptosis in macrophages infected with pathogenicLeptospiraspecies

Ojcius

Sun

et al. 2013

Cell Microbiol

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SummaryPathogenic Leptospira species, the causative agents of leptospirosis, have been shown to induce macrophage apoptosis through caspaseindependent, mitochondrion-related apoptosis inducing factor (AIF) and endonuclease G (EndoG), but the signalling pathway leading to AIF/EndoGbased macrophage apoptosis remains unknown. Here we show that infection of Leptospira interrogans caused a rapid increase in reactive oxygen species (ROS), DNA damage, and intranuclear foci of 53BP1 and phosphorylation of H2AX (two DNA damage indicators) in wild-type p53-containing mouse macrophages and p53-deficient human macrophages. Most leptospire-infected cells stayed at the G 1 phase, whereas depletion or inhibition of p53 caused a decrease of the G1-phase cells and the early apoptotic ratios. Infection with spirochaetes stimulated a persistent activation of p53 and an early activation of Akt through phosphorylation. The intranuclear translocation of p53, increased expression of p53-dependent p21 Cip1/WAF1

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Section: Discussionsupporting

confidence: 83%

p53 signalling controls cell cycle arrest and caspase-independent apoptosis in macrophages infected with pathogenicLeptospiraspecies

Ojcius

Sun

et al. 2013

Cell Microbiol

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“…Some researches have reported that the antitumor effect of doxycycline is associated with different levels of p53 in hepatocellular carcinoma [18]. Another study demonstrates that doxycycline can induce apoptosis in human pancreatic and colon cancer cells through caspase-dependent way [19]–[20].…”

Section: Discussionmentioning

confidence: 99%

The Inhibitory Effect of Doxycycline on Cisplatin-Sensitive and -Resistant Epithelial Ovarian Cancer

et al. 2014

PLoS ONE

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BackgroundDetecting a new effective and hypotoxic anticancer drug is an emerging new strategy for cancer chemotherapy. Doxycycline (DC) is a kind of antibiotics but also inhibits tumorigenesis.MethodsMTT and cell invasion assay, flow cytometry, western-blot analysis and nude mice were used to investigate the effects and underlying mechanisms of doxycycline on epithelial ovarian cancer cells.ResultsDoxycycline inhibited the proliferation and invasion of SKOV3 and SKOV3/DDP; induced moderate apoptosis of SKOV3/DDP. CXCR4 expression at both mRNA and protein levels was downregulated in both cell lines when treated with doxycycline. Akt and ERK1/2 were involved in doxycycline effect on cell proliferation of SKOV3 but not of SKOV3/DDP. Akt and EKR1/2 phosphorylation were activated by SDF-1α, which was then inhibited by doxycycline in SKOV3. Pro-caspase-3 expression was significantly higher in SKOV3 than that in SKOV3/DDP which was upregulated when treated with doxycycline. In vivo, doxycycline inhibited peritoneal tumor xenograft and decreased malignant ascites.ConclusionDoxycycline not only has an inhibitory effect on ovarian cancer, but also can increase sensitivity to cisplatin. SDF-1α/CXCR4-regulated Akt and ERK 1/2 activations are probably involved in the antitumor effect of doxycycline on SKOV3 cells, while upregulation of pro-caspase-3 may be the main mechanism involved in SKOV3/DDP cells.

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“…Thus, Fas proteins, which are increased by DOX, interact with FasL on T cells and result in Fas-mediated death of T cells. Furthermore, DOX changes the expression pattern of a multitude of genes involved in cell cycle regulation (p53, CDK10, and Gadd45) and apoptosis and cell damage (Fas and Bax) [13][14][15][16] . The p53 tumor suppressor gene, which is an essential transcription factor involved in cell cycle checkpoints, upregulates cell cycle modulators such as the cyclin-dependent kinase inhibitor p21 and GADD45, which is rapidly induced by genotoxic reagents [17] .…”

Section: Introductionmentioning

confidence: 99%

“…The molecular mechanisms governing the relationship between DNA damage, cell cycle arrest at G 2 /M, and inhibition of cell division remain poorly defined [18] . High levels of induction of p53 may result in apoptosis, while low expression of p53 may cause cell cycle arrest without cell death [14] . The GADD45 family is rapidly induced in response to pathological stimuli such as hypoxia, irradiation, and genotoxic drugs.…”

Section: Introductionmentioning

confidence: 99%

Doxorubicin Exerts Cytotoxic Effects through Cell Cycle Arrest and Fas-Mediated Cell Death

2009

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Doxorubicin (DOX) is involved in the induction of DNA damage, inhibition of cell proliferation, impairment of mitochondria, and cell death. To determine the biological effects of DOX in murine lymphocytes, we analyzed cell proliferation, cell cycle status, and apoptosis in Ba/F3 and EL4 lymphoid cells. DOX treatment resulted in significant cellular morphological alteration with increased intracellular granularity and cell size. DOX inhibited cell proliferation through cell cycle arrest at the G₂/M phase as well as by cell death. In addition, DOX treatment dramatically upregulated Fas expression and enhanced caspase activation to promote intracellular apoptotic signaling for cell death. Treatment with an agonistic antibody stimulated Fas and accelerated the cell death effects. In conclusion, we demonstrate that DOX induces cell cycle arrest and apoptosis by increased Fas expression and ultimately results in enhanced cell death.

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Different levels of p53 induced either apoptosis or cell cycle arrest in a doxycycline-regulated hepatocellular carcinoma cell line in vitro

Cited by 68 publications

References 21 publications

p53 signalling controls cell cycle arrest and caspase-independent apoptosis in macrophages infected with pathogenicLeptospiraspecies

p53 signalling controls cell cycle arrest and caspase-independent apoptosis in macrophages infected with pathogenicLeptospiraspecies

The Inhibitory Effect of Doxycycline on Cisplatin-Sensitive and -Resistant Epithelial Ovarian Cancer

Doxorubicin Exerts Cytotoxic Effects through Cell Cycle Arrest and Fas-Mediated Cell Death

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