Pharmacological Ascorbate Enhances Chemotherapies in Pancreatic Ductal Adenocarcinoma

Brianne R. O'Leary; Elena K. Ruppenkamp; Garett J. Steers; Juan Du; Rory S. Carroll; Brett A. Wagner; Garry R. Buettner; Joseph J. Cullen

doi:10.1097/MPA.0000000000002086

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Pharmacological Ascorbate Enhances Chemotherapies in Pancreatic Ductal Adenocarcinoma

Journal article

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Peer reviewed

Pharmacological Ascorbate Enhances Chemotherapies in Pancreatic Ductal Adenocarcinoma

Brianne R. O'Leary, Elena K. Ruppenkamp, Garett J. Steers, Juan Du, Rory S. Carroll, Brett A. Wagner, Garry R. Buettner and Joseph J. Cullen

Pancreas, Vol.51(6), pp.684-693

07/01/2022

DOI: 10.1097/MPA.0000000000002086

PMCID: PMC9547864

PMID: 36099493

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https://www.ncbi.nlm.nih.gov/pmc/articles/9547864View

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Abstract

Objectives Pharmacological ascorbate (P-AscH(-), high-dose, intravenous vitamin C) has shown promise as an adjuvant therapy for pancreatic ductal adenocarcinoma (PDAC) treatment. The objective of this study was to determine the effects of P-AscH(-) when combined with PDAC chemotherapies. Methods Clonogenic survival, combination indices, and DNA damage were determined in human PDAC cell lines treated with P-AscH(-) in combination with 5-fluorouracil, paclitaxel, or FOLFIRINOX (combination of leucovorin, 5-fluorouracil, irinotecan, oxaliplatin). Tumor volume changes, overall survival, blood analysis, and plasma ascorbate concentration were determined in vivo in mice treated with P-AscH(-) with or without FOLFIRINOX. Results P-AscH(-) combined with 5-fluorouracil, paclitaxel, or FOLFIRINOX significantly reduced clonogenic survival in vitro. The DNA damage, measured by gamma H2AX protein expression, was increased after treatment with P-AscH(-), FOLFIRINOX, and their combination. In vivo, tumor growth rate was significantly reduced by P-AscH(-), FOLFIRINOX, and their combination. Overall survival was significantly increased by the combination of P-AscH(-) and FOLFIRINOX. Treatment with P-AscH(-) increased red blood cell and hemoglobin values but had no effect on white blood cell counts. Plasma ascorbate concentrations were significantly elevated in mice treated with P-AscH(-) with or without FOLFIRINOX. Conclusions The addition of P-AscH(-) to standard of care chemotherapy has the potential to be an effective adjuvant for PDAC treatment.

Gastroenterology & Hepatology

Life Sciences & Biomedicine

Science & Technology

Details

Title: Subtitle: Pharmacological Ascorbate Enhances Chemotherapies in Pancreatic Ductal Adenocarcinoma
Creators: Brianne R. O'Leary - University of Iowa
Elena K. Ruppenkamp - From the Department of Surgery.
Garett J. Steers - University of Iowa
Juan Du - University of Iowa
Rory S. Carroll - University of Iowa
Brett A. Wagner - University of Iowa
Garry R. Buettner - University of Iowa
Joseph J. Cullen - Univ Iowa, Dept Surg, Carver Coll Med, Iowa City, IA 52242 USA
Resource Type: Journal article
Publication Details: Pancreas, Vol.51(6), pp.684-693
DOI: 10.1097/MPA.0000000000002086
PMID: 36099493
PMCID: PMC9547864
NLM abbreviation: Pancreas
ISSN: 0885-3177
eISSN: 1536-4828
Publisher: Lippincott Williams & Wilkins
Number of pages: 10
Grant note: P01 CA217797; T32 CA148062 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
Language: English
Date published: 07/01/2022
Academic Unit: Surgery; Radiation Oncology
Record Identifier: 9984313075802771

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