Synergism of arsenic trioxide and MG132 in Raji cells attained by targeting BNIP3, autophagy, and mitochondria with low doses of valproic acid and vincristine

Cavaliere, Victoria; Lombardo, Tomás; Costantino, Susana N.; Kornblihtt, Laura; Álvarez, Élida; Blanco, Guillermo

doi:10.1016/j.ejca.2014.09.012

Cited by 15 publications

(16 citation statements)

References 60 publications

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“…Consistent with our results, SAHA combined with cisplatin or decitabine can reinforce the antitumor effect on oral squamous cancer cells . MG132 combined with cisplatin or arsenic trioxide can enhance the drug sensitivity of ovarian cancer or Raji cells . Considering these findings, SAHA and MG132 can be used synergistically to eliminate neuroblastoma cells.…”

Section: Discussionsupporting

confidence: 90%

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ING5‐mediated antineuroblastoma effects of suberoylanilide hydroxamic acid

Jiang

Yang

et al. 2018

Cancer Medicine

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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.

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Section: Discussionsupporting

confidence: 90%

“…31 MG132 combined with cisplatin or arsenic trioxide can enhance the drug sensitivity of ovarian cancer 32 or Raji cells. 33 Considering these findings, SAHA and MG132 can be used synergistically to eliminate neuroblastoma cells.…”

Section: Discussionmentioning

confidence: 99%

ING5‐mediated antineuroblastoma effects of suberoylanilide hydroxamic acid

Jiang

Yang

et al. 2018

Cancer Medicine

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“…Both drugs exposure caused the suppression of tumor growth in nude mice by inducing apoptosis and inhibiting proliferation, but hepatic and renal toxicity occurred. Other examples include the combination of MG132 with cisplatin or arsenic trioxide that could increase sensitivity to drug therapy in ovarian cancer or Raji cells …”

Section: Resultsmentioning

confidence: 99%

Inhibition of human constitutive 20S proteasome and 20S immunoproteasome with novel N‐terminally modified peptide aldehydes and their antitumor activity

et al. 2018

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The conversion of primary structures of novel, highly selective and sensitive, internally quenched peptide substrates of the human 20S proteasome into peptide aldehydes is presented. Such covalent and reversible inhibitors differ in their primary structures and chemical moieties attached to their N‐terminal amino group. Inhibitory potency is primarily tested against proteolytic subunits of human constitutive 20S proteasome (β1c, β2c, and β5c subunits), but in some cases, also against 20S immunoproteasome β5i. Most of the peptide aldehydes act nonspecifically and bind equipotently to the corresponding proteolytic subunits of both forms of proteasome (β5c and β5i). Two inhibitors are 2.7‐times more specific for immunoproteasome over its constitutive counterpart. The antitumor activity of the selected inhibitors and MG132 (used here as the reference) is analyzed using MTT assay against nonmalignant human fetal osteoblastic hFOB 1.19, malignant human osteosarcoma MG‐63, human pancreatic cancer MiaPaCa‐2, and human acute leukemia Jurkat T cell lines. All inhibitors tested are able to decrease cell viability in a concentration‐dependent manner. One of the peptide aldehydes exerted stronger, as compared to the MG132, activity against human glioblastoma cell line U87‐MG. Moreover, its combination with dinaciclib, which is a novel, potent inhibitor of cyclin‐dependent kinases, reduces cellular metabolic activity more potently as compared to either proteasome inhibitor or dinaciclib alone.

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“…The combination of MG132 with cisplatin or arsenic trioxide could increase sensitivity to drug therapy in ovarian cancer [37] or Raji cells [38]. But the serum toxicity of combined drugs in nude mice was not reported.…”

Section: Discussionmentioning

confidence: 99%

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

Zhao¹,

Liu²,

Yang

et al. 2016

Oncotarget

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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.

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Synergism of arsenic trioxide and MG132 in Raji cells attained by targeting BNIP3, autophagy, and mitochondria with low doses of valproic acid and vincristine

Cited by 15 publications

References 60 publications

ING5‐mediated antineuroblastoma effects of suberoylanilide hydroxamic acid

ING5‐mediated antineuroblastoma effects of suberoylanilide hydroxamic acid

Inhibition of human constitutive 20S proteasome and 20S immunoproteasome with novel N‐terminally modified peptide aldehydes and their antitumor activity

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

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