Introduction of WT-TP53 into pancreatic cancer cells alters sensitivity to chemotherapeutic drugs, targeted therapeutics and nutraceuticals

Abrams, Stephen L.; Lertpiriyapong, Kvin; Yang, Li V.; Martelli, Alberto M.; Cocco, Lucio; Ratti, Stefano; Falasca, Marco; Murata, Ramiro Mendonça; Rosalen, Pedro Luiz; Lombardi, Paolo; Libra, Massimo; Candido, Saverio; Montalto, Giuseppe; Cervello, Melchiorre; Steelman, Linda S.; McCubrey, James A.

doi:10.1016/j.jbior.2018.06.002

Cited by 28 publications

(35 citation statements)

References 141 publications

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“…Previously, we and others have examined the roles of TP53 in the sensitivity of hematopoietic, prostate and pancreatic cells and other cancer types to chemotherapeutic drugs and, in some cases, radiation (Lehmann et al, 2007' McCubrey et al, 2008Chappell et al, 2012;Abrams et al, 2017;Steelman et al, 2017;Abrams et al, 2018;Abrams et al, 2019). We observed that introduction of dominant negative (DN)-TP53 into FL5.12 hematopoietic cells increased their chemoresistance (McCubrey et al, 2008;Abrams et al, 2017;Steelman et al, 2017).…”

Section: Pancreatic Cancer Genetics: Some Common Oncogenes/tumor Suppmentioning

confidence: 92%

“…The development of PDAC is complex and includes both environmental, as well as, genetic risk factors (Klein, 2012). We have recently summarized the risk and genetic factors associated with development of pancreatic cancer (Abrams et al, 2018(Abrams et al, , 2019Candido et al, 2018). Some of the risk factors for PDAC development in the USA are race and gender based, as well as, diabetes and obesity.…”

Section: Pancreatic Cancer: a Devastating Cancer With Few Effective Tmentioning

confidence: 99%

“…Introduction of WT-TP53 was observed to increase the sensitivity of certain PDAC cells to certain chemotherapeutic drugs, signal transduction inhibitors and nutraceuticals (Abrams et al, 2018(Abrams et al, , 2019. Reprogramming TP53 is a potent target for pancreatic cancer therapy (Saghatelian et al, 2017).…”

Section: Pancreatic Cancer Genetics: Some Common Oncogenes/tumor Suppmentioning

confidence: 99%

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Effects of the MDM-2 inhibitor Nutlin-3a on PDAC cells containing and lacking WT-TP53 on sensitivity to chemotherapy, signal transduction inhibitors and nutraceuticals

Candido

Abrams

Steelman

et al. 2019

Advances in Biological Regulation

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Mutations at the TP53 gene are readily detected (approximately 50-75%) in pancreatic ductal adenocarcinoma (PDAC) patients. TP53 was previously thought to be a difficult target as it is often mutated, deleted or inactivated on both chromosomes in certain cancers. In the following study, the effects of restoration of wild-type (WT) TP53 activity on the sensitivities of MIA-PaCa-2 pancreatic cancer cells to the MDM2 inhibitor nutlin-3a in combination with chemotherapy, targeted therapy, as well as, nutraceuticals were examined. Upon introduction of the WT-TP53 gene into MIA-PaCa-2 cells, which contain a TP53 gain of function (GOF) mutation, the sensitivity to the MDM2 inhibitor increased. However, effects of nutlin-3a were also observed in MIA-PaCa-2 cells lacking WT-TP53, as upon co-treatment with nutlin-3a, the sensitivity to certain inhibitors, chemotherapeutic drugs and nutraceuticals increased. Interestingly, co-treatment with nutlin-3a and certain chemotherapeutic drug such as irinotecan and oxaliplatin resulted in antagonistic effects in cells both lacking and containing WT-TP53 activity. These studies indicate the sensitizing abilities that WT-TP53 activity can have in PDAC cells which normally lack WT-* Corresponding author.

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Section: Pancreatic Cancer Genetics: Some Common Oncogenes/tumor Suppmentioning

confidence: 92%

Section: Pancreatic Cancer: a Devastating Cancer With Few Effective Tmentioning

confidence: 99%

Section: Pancreatic Cancer Genetics: Some Common Oncogenes/tumor Suppmentioning

confidence: 99%

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Effects of the MDM-2 inhibitor Nutlin-3a on PDAC cells containing and lacking WT-TP53 on sensitivity to chemotherapy, signal transduction inhibitors and nutraceuticals

Candido

Abrams

Steelman

et al. 2019

Advances in Biological Regulation

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“…We have recently reviewed various modified BBR compounds that have been developed (McCubrey et al, 2017;Abrams et al, 2018;Abrams et al, 2019). In this current manuscript, we will summarize some novel advances in the field.…”

Section: Chemically-modified Bbrs-enhancing Effects Of Bbr By Medicinmentioning

confidence: 99%

“…Previously, we have summarized many of the key genetic and biological factors implicated in pancreatic cancer Abrams et al, 2018Abrams et al, , 2019McCubrey et al, 2018). Although various genetics and environmental factors may be involved in pancreatic cancer, few remedies have been developed to treat this devastating disease beyond surgery and chemotherapy which, unfortunately, only have minimal positive effects on patient survival.…”

Section: Introductionmentioning

confidence: 99%

Abilities of berberine and chemically modified berberines to interact with metformin and inhibit proliferation of pancreatic cancer cells

Akula

Candido

Libra

et al. 2019

Advances in Biological Regulation

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A B S T R A C TPancreatic cancer is devastating cancer worldwide with few if any truly effective therapies. Pancreatic cancer has an increasing incidence and may become the second leading cause of death from cancer. Novel, more effective therapeutic approaches are needed as pancreatic cancer patients usually survive for less than a year after being diagnosed. Control of blood sugar levels by the prescription drug metformin in diseases such as diabetes mellitus has been examined in association with pancreatic cancer. While the clinical trials remain inconclusive, there is hope that certain diets and medications may affect positively the outcomes of patients with pancreatic and other cancers. Other natural compounds may share some of the effects of metformin. One "medicinal" fruit consumed by millions worldwide is berberine (BBR). Metformin and BBR both activate AMP-activated protein kinase (AMPK) which is a key mediator of glucose metabolism.

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Identification of Protein Markers Predictive of Drug-Specific Survival Outcome in Cancers

Lin

Zhou

Xiao

et al. 2021

Bioinformatics Research and Applications

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Introduction of WT-TP53 into pancreatic cancer cells alters sensitivity to chemotherapeutic drugs, targeted therapeutics and nutraceuticals

Cited by 28 publications

References 141 publications

Effects of the MDM-2 inhibitor Nutlin-3a on PDAC cells containing and lacking WT-TP53 on sensitivity to chemotherapy, signal transduction inhibitors and nutraceuticals

Effects of the MDM-2 inhibitor Nutlin-3a on PDAC cells containing and lacking WT-TP53 on sensitivity to chemotherapy, signal transduction inhibitors and nutraceuticals

Abilities of berberine and chemically modified berberines to interact with metformin and inhibit proliferation of pancreatic cancer cells

Identification of Protein Markers Predictive of Drug-Specific Survival Outcome in Cancers

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