The epigenetic agents suberoylanilide hydroxamic acid and 5-AZA-2′ deoxycytidine decrease cell proliferation, induce cell death and delay the growth of MiaPaCa2 pancreatic cancer cells in vivo

Susanto, Johana M.; Colvin, Emily K.; Pinese, Mark; Chang, David K.; Mawson, Amanda; Caldon, C. Elizabeth; Musgrove, Elizabeth A.; Henshall, Susan M.; Sutherland, Robert L.; Biankin, Andrew V.; Scarlett, Christopher J.

doi:10.3892/ijo.2015.2894

Cited by 17 publications

(18 citation statements)

References 62 publications

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“…HDAC Inhibitor, DNMT Inhibitor SAHA, a HDAC inhibitor and 5-AZA-dc, a DNA methyltransferase (DNMT) inhibitor, decreases cell proliferation, increases cell death, lowers DNA synthesis and induces p21, leading to a G1 arrest [136]. These results indicate a potential role in chemopreventive treatment, which is proved in studies in cell culture, mice and humans [136][137][138].…”

Section: T-cupmmentioning

confidence: 63%

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Chemoprevention and Treatment of Pancreatic Cancer: Update and Review of the Literature

Benzel

Fendrich

2018

Digestion

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Background: Pancreatic ductal adenocarcinoma is one of the most lethal types of cancer with a 5-year survival rate of around 7%. Due to the relatively poor prognosis, the potential need of an effective chemoprevention is highly needed. Summary: Different risk factors like smoking or hereditary tumour syndromes should be known for early detection of pancreatic intraepithelial neoplasia. Chemopreventive dietary agents include curcumin, capsaicin and flavonoid, whereas potential chemopreventive drugs compromise aspirin, metformin or statins. This review aims to give an overview on potential risk factors for the development of pancreatic cancer. Furthermore, we try to summarise known chemopreventive agents to support the fight against this lethal disease. Key Messages: On the one hand, there are natural agents that exhibit preventive properties and can lead to the prohibition of pancreatic cancer. On the other hand, there are drugs and agents that are currently used in other contexts and are thus already approved and studied in terms of their mechanisms of effects and the related secondary effects.

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Section: T-cupmmentioning

confidence: 63%

“…These results indicate a potential role in chemopreventive treatment, which is proved in studies in cell culture, mice and humans [136][137][138]. Because of many side effects of HDAC and DNMT inhibitors, the chemopreventive effects are not sufficient enough to use them as a chemopreventive drug [139,140].…”

Section: T-cupmmentioning

confidence: 94%

Chemoprevention and Treatment of Pancreatic Cancer: Update and Review of the Literature

Benzel

Fendrich

2018

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“…Since Akt signaling controls cell cycle ( 85 ), it is likely that Akt is involved in entinostat-mediated doxorubicin sensitization. While entinostat alone inhibited the expression of cell cycle proteins, its combination with decitabine (DNMTi) in pancreatic cancer increased expression of p21 to reinstitute cell cycle control and inhibit tumor growth, likely due to increased acetylation of histone H3 and demethylation of the p21 promoter ( 86 ).…”

Section: Epigenetic Drug-induced Sensitization Mechanismsmentioning

confidence: 99%

Understanding the Mechanisms by Which Epigenetic Modifiers Avert Therapy Resistance in Cancer

2020

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The development of resistance to anti-cancer therapeutics remains one of the core issues preventing the improvement of survival rates in cancer. Therapy resistance can arise in a multitude of ways, including the accumulation of epigenetic alterations in cancer cells. By remodeling DNA methylation patterns or modifying histone proteins during oncogenesis, cancer cells reorient their epigenomic landscapes in order to aggressively resist anti-cancer therapy. To combat these chemoresistant effects, epigenetic modifiers such as DNA hypomethylating agents, histone deacetylase inhibitors, histone demethylase inhibitors, along with others have been used. While these modifiers have achieved moderate success when used either alone or in combination with one another, the most positive outcomes were achieved when they were used in conjunction with conventional anti-cancer therapies. Epigenome modifying drugs have succeeded in sensitizing cancer cells to anti-cancer therapy via a variety of mechanisms: disrupting pro-survival/anti-apoptotic signaling, restoring cell cycle control and preventing DNA damage repair, suppressing immune system evasion, regulating altered metabolism, disengaging pro-survival microenvironmental interactions and increasing protein expression for targeted therapies. In this review, we explore different mechanisms by which epigenetic modifiers induce sensitivity to anti-cancer therapies and encourage the further identification of the specific genes involved with sensitization to facilitate development of clinical trials.

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“…Now, it is recognized HDACIs induce an array of cellular effects [69,82,83]. They stimulate cell cycle arrest by upregulating p21Cip1 and downregulating cyclins [69,84,85]. They also do the following: 1) Induce intrinsic and extrinsic apoptosis pathways causing apoptosis [75,86,87].…”

Section: Histone Deacetylase Inhibitors (Hdacis)mentioning

confidence: 99%

Histone Deacetylase Inhibitors as Multitarget-Directed Epi-Drugs in Blocking PI3K Oncogenic Signaling: A Polypharmacology Approach

Ranganna¹,

Selvam²,

Shivachar³

et al. 2020

IJMS

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Genetic mutations and aberrant epigenetic alterations are the triggers for carcinogenesis. The emergence of the drugs targeting epigenetic aberrations has provided a better outlook for cancer treatment. Histone deacetylases (HDACs) are epigenetic modifiers playing critical roles in numerous key biological functions. Inappropriate expression of HDACs and dysregulation of PI3K signaling pathway are common aberrations observed in human diseases, particularly in cancers. Histone deacetylase inhibitors (HDACIs) are a class of epigenetic small-molecular therapeutics exhibiting promising applications in the treatment of hematological and solid malignancies, and in non-neoplastic diseases. Although HDACIs as single agents exhibit synergy by inhibiting HDAC and the PI3K pathway, resistance to HDACIs is frequently encountered due to activation of compensatory survival pathway. Targeted simultaneous inhibition of both HDACs and PI3Ks with their respective inhibitors in combination displayed synergistic therapeutic efficacy and encouraged the development of a single HDAC-PI3K hybrid molecule via polypharmacology strategy. This review provides an overview of HDACs and the evolution of HDACs-based epigenetic therapeutic approaches targeting the PI3K pathway.

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The epigenetic agents suberoylanilide hydroxamic acid and 5-AZA-2′ deoxycytidine decrease cell proliferation, induce cell death and delay the growth of MiaPaCa2 pancreatic cancer cells in vivo

Cited by 17 publications

References 62 publications

Chemoprevention and Treatment of Pancreatic Cancer: Update and Review of the Literature

Chemoprevention and Treatment of Pancreatic Cancer: Update and Review of the Literature

Understanding the Mechanisms by Which Epigenetic Modifiers Avert Therapy Resistance in Cancer

Histone Deacetylase Inhibitors as Multitarget-Directed Epi-Drugs in Blocking PI3K Oncogenic Signaling: A Polypharmacology Approach

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