Tributyrin induces differentiation, growth arrest and apoptosis in androgen‐sensitive and androgen‐resistant human prostate cancer cell lines

Maier, Simone; Reich, Ella Dumbravia; Martin, Renate; Bachem, Max G.; Altug, Vedat; Hautmann, Richard E.; Gschwend, Jürgen E.

doi:10.1002/1097-0215(20001015)88:2<245::aid-ijc16>3.3.co;2-o

Cited by 20 publications

(36 citation statements)

References 13 publications

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“…Incubation with equimolar concentrations of tributyrin revealed stronger dose-dependent growth-inhibitory effects (data not shown). This is in accordance with our previous study, where further detailed data were presented (Maier et al, 2000).…”

Section: Butyrate-induced Growth Inhibition In Vitrosupporting

confidence: 94%

“…In our previous study, we have shown several in vitro effects caused by treatment of PC3, TSU-Pr1 and LNCaP cells with sodium butyrate or tributyrin (Maier et al, 2000). These effects included cell swelling, nuclear disruption, cell cycle arrest in the G1 phase and dose-dependent induction of apoptosis.…”

Section: Discussionmentioning

confidence: 95%

“…Quantitative assessment of apoptosis in implanted tumours The detection of apoptotic cells was performed as described previously (Maier et al, 2000). Tumours were sampled 5 days after seeding and embedded in paraffin.…”

Section: Chorioallantois Membranementioning

confidence: 99%

“…It has been shown that tributyrin can induce differentiation in human myeloid leukaemia cells, murine erythroleukaemia cells (Chen and Breitman, 1994), MCF-7 mammary carcinoma cells (Heerdt et al, 1999) and HT-29 colon cancer cells (Schroder et al, 1998). We have previously demonstrated that butyrates strongly induce in vitro growth inhibition and apoptosis in different human prostate cancer cell lines (Maier et al, 2000).…”

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confidence: 94%

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Sodium butyrate and tributyrin induce in vivo growth inhibition and apoptosis in human prostate cancer

et al. 2004

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Histone deacetylase inhibitors (HDACs) are known to exhibit antiproliferative effects on various carcinoma cells. In this study, the in vivo efficiency of two HDACs, sodium butyrate and tributyrin, on prostate cancer growth inhibition were investigated. To gain an insight into the possible underlying pathways, cell culture experiments were performed focusing on the expression of p21, Rb and cmyc. For in vivo testing, prostate cancer cell lines (PC3 and TSU-Pr1) were seeded on the chorioallantois membrane (CAM) and implanted in a xenograft model using nude mice. Standard Western blot analysis was performed for protein expression of p21, Rb and c-myc in HDAC-treated vs untreated prostate cancer cells. Both sodium butyrate and tributyrin had a considerable treatment effect on microtumours on the chicken egg at already very low concentrations of 0.1 mM. Tributyrin-treated tumours showed the strongest effect with 38% apoptotic nuclei in the prostate cancer cell line PC3. In the mouse model, there was almost no difference between sodium butyrate and tributyrin. In untreated animals the tumours were almost double the size 4 weeks after implantation. Tumours of the treatment groups had a significantly lower percentage of Ki-67-positive-stained nuclei. As demonstrated by Western blot analysis, these effects seem to be independent of p53 status and a pathway via p21 -Rb -c-myc is possibly involved. In this study we have demonstrated a substantial in vivo treatment effect, which can be induced by the application of sodium butyrate or the orally applicable tributyrin in human prostate cancer. The given results may provide the rationale to apply these drugs in well-controlled clinical trials in patients being at high risk of recurrence after specific therapy or in patients with locally or distant advanced prostate cancer.

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Section: Butyrate-induced Growth Inhibition In Vitrosupporting

confidence: 94%

Section: Discussionmentioning

confidence: 95%

Section: Chorioallantois Membranementioning

confidence: 99%

mentioning

confidence: 94%

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Sodium butyrate and tributyrin induce in vivo growth inhibition and apoptosis in human prostate cancer

et al. 2004

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“…Among those chemoagents targeting epigenetics, HDAC inhibitors are known to exhibit antiproliferative effects on cancer cells through modulating transcription [23,35], and are considered as potential therapeutic agents against malignancies. Our results showed a clear increase in hTERT expression following FR901228 treatment of oral cancer cell lines.…”

Section: Discussionmentioning

confidence: 99%

Effects of histone deacetylase inhibitor FR901228 on the expression level of telomerase reverse transcriptase in oral cancer

Murakami

Asaumi

Kawai

et al. 2005

Cancer Chemother Pharmacol

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We speculated whether or not the expression level of telomerase reverse transcriptase (hTERT) would be modulated by agents targeting epigenetics in oral cancer cell lines. Although hTERT is known to be targeted by epigenetic changes, it remains unclear how chemoagents targeting epigenetics work on hTERT transcription. In the present study, the epigenetic effects of histone deacetylase (HDAC) inhibitor FR901228 on hTERT transcription were analysed by RT-PCR in oral cancer cell lines. The mRNA expression of hTERT was upregulated after exposure to FR901228 in hTERT-negative Hep2 cells, even in the hTERT highly expressed SAS and KB cells.Moreover, co-treatment of protein synthesis inhibitor cycloheximide (CHX) resulted in the induction of hTERT transcription by FR901228. This suggests that the induction of hTERT by FR901228 requires de novo protein synthesis to some extent and is more likely a direct than an indirect effect on epigenetic changes such as histone acetylation / deacetylation. We further examined the effect of FR901228 on c-myc protein, which is one of the main hTERT transcription activators. FR901228 repressed c-myc protein only in the absence of CHX, dependent of the enhancement of de novo protein synthesis. Our results indicate that c-myc protein is repressed indirectly by FR901228 but may not contribute FR901228-induced hTERT transcription. The present study showed that the HDAC inhibitor FR901228 induced the hTERT gene by a complex mechanism that involved other transcription factors except for c-myc, in addition to the inhibition of histone deacetylation.

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Histone deacetylase inhibitors suppress telomerase reverse transcriptase mrna expression in prostate cancer cells

Suenaga

Soda

Oka

et al. 2001

Intl Journal of Cancer

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Telomerase activity is involved in cellular immortality. We have recently demonstrated that telomerase activity is closely associated with cell proliferation in prostate cancers. Telomerase is composed primarily of the catalytic subunit (hTERT) and the RNA template (hTERC), and hTERT expression is regulated by several factors such as c-MYC and p21Waf1 . Histone deacetylase (HDAC) inhibitors are known to modulate transcription and exhibit antiproliferative effects on cancer cells. The present study was designed to evaluate the effects of HDAC inhibitors on hTERT mRNA expression in prostate cancer cells. LNCaP and PC-3 cells were treated with HDAC inhibitors, trichostatin A (TSA) and sodium butyrate (NaB); mRNA expression and telomerase activity were evaluated by RT-PCR and the TRAP assay, respectively. In LNCaP cells, hTERT mRNA expression was suppressed at 1 and 3 hr after treatment with 1 M TSA and 4 mM NaB, respectively, followed by inhibition of telomerase activity. The inhibition of hTERT mRNA expression preceded suppression of cell proliferation. In PC-3 cells, TSA and NaB also inhibited cell proliferation, hTERT mRNA expression and telomerase activity. In both cell lines, TSA and NaB had no effect on hTERC expression, or on expression of c-myc and p21Waf1 mRNA. These effects of TSA and NaB were unlikely to be consequences of cell cycle arrest, apoptosis, or cell differentiation. Thus, HDAC inhibitors down-regulated telomerase activity via suppression of hTERT mRNA expression. Our study identified a novel mechanism for the antiproliferative effects of HDAC inhibitors on prostate cancer cells.

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Tributyrin induces differentiation, growth arrest and apoptosis in androgen‐sensitive and androgen‐resistant human prostate cancer cell lines

Cited by 20 publications

References 13 publications

Sodium butyrate and tributyrin induce in vivo growth inhibition and apoptosis in human prostate cancer

Sodium butyrate and tributyrin induce in vivo growth inhibition and apoptosis in human prostate cancer

Effects of histone deacetylase inhibitor FR901228 on the expression level of telomerase reverse transcriptase in oral cancer

Histone deacetylase inhibitors suppress telomerase reverse transcriptase mrna expression in prostate cancer cells

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