Suberoylanilide hydroxamic acid enhances chemosensitivity to 5-fluorouracil in hepatocellular carcinoma via inhibition of thymidylate synthase

Liao, Bo; Liang, Huifang; Chen, Jin; Liu, Qiumeng; Zhang, Bixiang; Chen, Xiaoping

doi:10.1007/s13277-015-3497-9

Cited by 12 publications

(15 citation statements)

References 41 publications

(64 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Reportedly, the combination of SAHA and XL184 synergistically induced cell apoptosis and inhibited tumor growth of prostate and lung cancer cells [19]. The similar results were observed in gastric [20] and hepatocellular [21] cancer cells, treated by oxaliplatin and SAHA. Therefore, they might be employed to treat the glioma if both hepatic and renal injuries are avoided and ameliorated in clinical practice.…”

Section: Discussionmentioning

confidence: 54%

SAHA and/or MG132 reverse the aggressive phenotypes of glioma cells: Anin vitroand vivo study

Zhao¹,

Liu²,

Yang

et al. 2016

Oncotarget

View full text Add to dashboard Cite

To elucidate the anti-tumor effects and molecular mechanisms of SAHA (a histone deacetylase inhibitor) and MG132 (a proteasome inhibitor) on the aggressive phenotypes of glioma cells, we treated U87 and U251 cells with SAHA or/and MG132, and detected phenotypes’ assays with phenotype-related molecules examined. It was found that SAHA or/and MG132 treatment suppressed proliferation in both concentration- and time-dependent manners, inhibited energy metabolism, migration, invasion and lamellipodia formation, and induced G2 arrest and apoptosis in the glioma cells. The treatment with SAHA increased the expression of acetyl-histones 3 and 4, which were recruited to the promoters of p21, p27, Cyclin D1, c-myc and Nanog to down-regulate their transcriptional levels. Expression of acetyl-histones 3 and 4 was higher in gliomas than normal brain tissues. Both drugs’ exposure suppressed tumor growth in nude mice by inducing apoptosis and inhibiting proliferation, but increased serum aminotransferase and creatinine. These results indicated that SAHA and/or MG132 may suppress the aggressive phenotypes of glioma cells. They might be employed to treat the glioma if both hepatic and renal injuries are prevented.

show abstract

Section: Discussionmentioning

confidence: 54%

SAHA and/or MG132 reverse the aggressive phenotypes of glioma cells: Anin vitroand vivo study

Zhao¹,

Liu²,

Yang

et al. 2016

Oncotarget

View full text Add to dashboard Cite

show abstract

“…Although some of these agents often demonstrate more potent antitumor effects than SAHA and romidepsin in preclinical testing, none have thus far demonstrated vastly superior clinical activity, or more favorable toxicity profiles, and accordingly none have yet been registered for clinical use except panobinostat (registered in FDA and EMEA). The antineoplastic effects of SAHA have been observed in various malignancies . In advanced leukemia and myelodysplastic syndrome, SAHA exposure induced significantly lower antileukemia activity than the maximum tolerated dose and inhibited the HDAC activity of peripheral blood and bone marrow blasts .…”

Section: Discussionmentioning

confidence: 99%

“…SAHA/Parthenolide combination promoted GSH depletion, Δψm reduction, and cytochrome c release and activated Caspase‐3 via histones H3 and H4 hyperacetylation or downregulated DNMT1 expression . SAHA and 5‐FU synergistically inhibited the proliferation of hepatocellular carcinoma cells by inducing G 0 /G 1 arrest and caspase‐dependent apoptosis . Cisplatin and SAHA dose dependently and synergistically reduced the viability of cholangiocarcinoma cells and induced cell apoptosis, accompanied by upregulation of p53 and p21 and downregulation of CDK4 and Bcl‐2 …”

Section: Discussionmentioning

confidence: 99%

“…The antineoplastic effects of SAHA have been observed in various malignancies. [9][10][11][12][13][14][15]17,[22][23][24][25][26][27][28] In advanced leukemia and myelodysplastic syndrome, SAHA exposure induced significantly lower antileukemia activity than the maximum tolerated dose and inhibited the HDAC activity of peripheral blood and bone marrow blasts. 29 Foster et al 30 found that co-administration of Bcl-2 inhibitor ABT-737 and SAHA induced apoptosis accompanied by Noxa upregulation, Bax activation, and mitochondrial dysfunction in PTEN-intact glioma cells.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

ING5‐mediated antineuroblastoma effects of suberoylanilide hydroxamic acid

Jiang

Yang

et al. 2018

Cancer Medicine

View full text Add to dashboard Cite

Neuroblastoma is the most common extracranial solid neuroendocrine cancer and is one of the leading causes of death in children. To improve clinical outcomes and prognosis, discovering new promising drugs and targeted medicine is essential. We found that applying Suberoylanilide hydroxamic acid (SAHA; Vorinostat, a histone deacetylase inhibitor) and MG132 (a proteasome inhibitor) to SH‐SY5Y cells synergistically suppressed proliferation, glucose metabolism, migration, and invasion and induced apoptosis and cell cycle arrest. These effects occurred both concentration and time dependently and were associated with the effects observed with inhibitor of growth 5 (ING5) overexpression. SAHA and MG132 treatment increased the expression levels of ING5, PTEN, p53, Caspase‐3, Bax, p21, and p27 but decreased the expression levels of 14‐3‐3, MMP‐2, MMP‐9, ADFP, Nanog, c‐myc, CyclinD1, CyclinB1, and Cdc25c concentration dependently, similar to ING5. SAHA may downregulate miR‐543 and miR‐196‐b expression to enhance the translation of ING5 protein, which promotes acetylation of histones H3 and H4. All three proteins (ING5 and acetylated histones H3 and H4) were recruited to the promoters of c‐myc, Nanog, CyclinD1, p21, and p27 for complex formation, thereby regulating the mRNA expression of downstream genes. ING5 overexpression and SAHA and/or MG132 administration inhibited tumor growth in SH‐SY5Y cells by suppressing proliferation and inducing apoptosis. The expression of acetylated histones H3 and ING5 may be closely linked to the tumor size of neuroblastomas. In summary, SAHA and/or MG132 can synergistically suppress the malignant phenotypes of neuroblastoma cells through the miRNA‐ING5‐histone acetylation axis and via proteasomal degradation, respectively. Therefore, the two drugs may serve as potential treatments for neuroblastoma.

show abstract

“…The cell viability assay was performed as described previously (24). HepG2.2.15 cells (2x10 3 per well) were seeded and cultured in 96-well plates for the indicated times.…”

Section: Reverse Transcription and Real-time Quantitative Pcr (Qpcr)mentioning

confidence: 99%

Regulation of ERK and AKT Pathways by Hepatitis B Virus X Protein via Notch1 Pathway in Hepatocellular Carcinoma

Liao

Zhou

Liang

et al. 2016

Preprint

Self Cite

View full text Add to dashboard Cite

Abstract. Hepatitis B virus (HBV) is the dominant risk factor for hepatocellular carcinoma (HCC). HBV X protein (HBx) plays crucial roles in HCC carcinogenesis. HBx interferes with several signaling pathways including the Notch1 pathway in HCC. In this study, we found that Notch1 was highly expressed in HCC, especially in large HCCs. Notch1 and HBx co-localized in HCC and their levels were positively correlated with each other. Notch1 expression was more elevated in HepG2.2.15 cells than that in HepG2 cells. HBx activated the Notch1 pathway in HepG2.2.15 cells. Suppression of HBx and the Notch1 pathway attenuated the growth of HepG2.2.15 cells. Notch1, ERK, and AKT pathways were inhibited after γ-secretase inhibitor treatment. Dual-specificity phosphatase 1 (DUSP1) and phosphatase and tensin homolog (PTEN) were upregulated after γ-secretase inhibitor treatment and Hes1 inhibition. Luciferase reporter assays showed that Hes1 suppressed the promoters of DUSP1 and PTEN genes, which was reversed by γ-secretase inhibitor treatment. Western blotting demonstrated that DUSP1 dephosphorylated pERK and PTEN dephosphorylated pAKT. Collectively, we found a link among HBx, the Notch1 pathway, DUSP1/PTEN, and ERK/AKT pathways, which influenced HCC cell survival and could be a therapeutic target for HCC treatment.

show abstract

Suberoylanilide hydroxamic acid enhances chemosensitivity to 5-fluorouracil in hepatocellular carcinoma via inhibition of thymidylate synthase

Cited by 12 publications

References 41 publications

SAHA and/or MG132 reverse the aggressive phenotypes of glioma cells: Anin vitroand vivo study

SAHA and/or MG132 reverse the aggressive phenotypes of glioma cells: Anin vitroand vivo study

ING5‐mediated antineuroblastoma effects of suberoylanilide hydroxamic acid

Regulation of ERK and AKT Pathways by Hepatitis B Virus X Protein via Notch1 Pathway in Hepatocellular Carcinoma

Contact Info

Product

Resources

About