Ascorbic acid and colon cancer: an oxidative stimulus to cell death depending on cell profile

Pires, Ana Salomé; Marques, Claúdia R.; Encarnação, João Crispim; Abrantes, Ana Margarida; Mamede, A.C.; Laranjo, Mafalda; Gonçalves, Ana Cristina; Sarmento‐Ribeiro, Ana Bela; Botelho, Maria Filomena

doi:10.1016/j.ejcb.2016.04.001

Cited by 42 publications

(35 citation statements)

References 54 publications

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“…At low doses, vitamin C has anti-oxidant activities (26,27), and many studies have demonstrated that vitamin C supplements can decrease oxidative stress (15,58,59). However, high-dose (millimolar) vitamin C treatment can increase oxidative stress (60)(61)(62), and previous studies showed that high-dose vitamin C can enhance intracellular H 2 O 2 , resulting in cancer cell death (37,63,64). Surprisingly, another study reported that low-dose (micromolar) vitamin C attenuated H 2 O 2 levels but enhanced the anticancer activities of MTX on hepatoma cells (15).…”

Section: Discussionmentioning

confidence: 99%

Combined treatment with vitamin C and methotrexate inhibits triple-negative breast cancer cell growth by increasing H2O2 accumulation and activating caspase-3 and p38 pathways

Liu

et al. 2017

Oncology Reports

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Methotrexate (MTX) is widely used as both an anticancer and anti-rheumatoid arthritis drug. Although MTX has been used to inhibit the growth of many cancer cells, it cannot effectively inhibit growth of triple-negative breast cancer cells (TNBC cells). Vitamin C is an antioxidant that can prevent oxidative stress. In addition, vitamin C has been applied as adjunct treatment for growth inhibition of cancer cells. Recent studies indicated that combined treatment with vitamin C and MTX may inhibit MCF-7 and MDA-MB-231 breast cancer cell growth through G2/M elongation. However, the mechanisms remain unknown. The aim of the present study was to determine whether combined treatment with low-dose vitamin C and MTX inhibits TNBC cell growth and to investigate the mechanisms of vitamin C/MTX-induced cytotoxicity. Neither low-dose vitamin C alone nor MTX alone inhibited TNBC cell growth. However, combined low-dose vitamin C and MTX had synergistic anti-proliferative/cytotoxic effects on TNBC cells. In addition, co-treatment increased H2O2 levels and activated both caspase-3 and p38 cell death pathways.

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Section: Discussionmentioning

confidence: 99%

Combined treatment with vitamin C and methotrexate inhibits triple-negative breast cancer cell growth by increasing H2O2 accumulation and activating caspase-3 and p38 pathways

Liu

et al. 2017

Oncology Reports

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“…The generation of ascorbyl- and H 2 O 2 radicals by PAA increases ROS stress in cancer cells (Du et al, 2012). These studies including preclinical and clinical were performed in solid tumors, such as glioblastoma (Herst et al, 2012), pancreatic cancer (Du et al, 2015), ovarian cancer (Ma et al, 2014), prostate cancer (Chen et al, 2012, Pollard et al, 2010), hepatoma (Verrax and Calderon, 2009), colon cancer (Pires et al, 2016), mesothelioma (Ranzato et al, 2011), breast cancer (Yun et al, 2015), bladder cancer (Gilloteaux et al, 2010), and neuroblastoma (Deubzer et al, 2010). Reports are lacking to show that PAA can be used as a pro-oxidant drug in the treatment of “liquid” tumors, where tumor cells are surrounded by blood.…”

Section: Discussionmentioning

confidence: 99%

Multiple Myeloma Tumor Cells are Selectively Killed by Pharmacologically-dosed Ascorbic Acid

Xia

Zhang

et al. 2017

EBioMedicine

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High-dose chemotherapies to treat multiple myeloma (MM) can be life-threatening due to toxicities to normal cells and there is a need to target only tumor cells and/or lower standard drug dosage without losing efficacy. We show that pharmacologically-dosed ascorbic acid (PAA), in the presence of iron, leads to the formation of highly reactive oxygen species (ROS) resulting in cell death. PAA selectively kills CD138+ MM tumor cells derived from MM and smoldering MM (SMM) but not from monoclonal gammopathy undetermined significance (MGUS) patients. PAA alone or in combination with melphalan inhibits tumor formation in MM xenograft mice. This study shows PAA efficacy on primary cancer cells and cell lines in vitro and in vivo.

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“…AA cytotoxicity is influenced by the increased expression of AA transporters that allows the entrance of AA into cells, where it releases the electrons necessary for superoxide radical and H 2 O 2 generation. It is also regulated by the mitochondria-dependent pathway mediated by a decrease in mitochondrial membrane potential (Ψm) and an increase in BAX/BCL-2 expression has been observed [ 29 ].…”

Section: Resultsmentioning

confidence: 99%

Ascorbic Acid in Colon Cancer: From the Basic to the Clinical Applications

Halabi

Bejjany

Nasr

et al. 2018

IJMS

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Given the safety and potential benefits of intravenous ascorbic acid (AA) administration in cancer patients, there is merit in further exploring this therapeutic concept. In this review, we discuss the potential benefits of intravenous AA administration on colorectal cancer and we specifically focus on its effect on glycolysis in mutant and wild type RAS. We perform a PubMed and Ovid MEDLINE search using ascorbic acid, intravenous vitamin C, KRAS mutation, BRAF mutation and colorectal cancer (CRC) as keywords. At the cellular level, colorectal cancer cells undergo a metabolic shift called the Warburg effect to allow for more glucose absorption and utilization of glycolysis. This shift also allows AA to enter which leads to a disruption in the Warburg effect and a shutdown of the downstream KRAS pathway in mutated KRAS colon cancer cells. At the clinical level, AA is associated with tumour regression in advanced disease and improved tolerability and side effects of standard therapy. Based on these findings, we conclude that further clinical trials are needed on a larger scale to examine the therapeutic benefits of AA in colon cancer.

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Ascorbic acid and colon cancer: an oxidative stimulus to cell death depending on cell profile

Cited by 42 publications

References 54 publications

Combined treatment with vitamin C and methotrexate inhibits triple-negative breast cancer cell growth by increasing H2O2 accumulation and activating caspase-3 and p38 pathways

Combined treatment with vitamin C and methotrexate inhibits triple-negative breast cancer cell growth by increasing H2O2 accumulation and activating caspase-3 and p38 pathways

Multiple Myeloma Tumor Cells are Selectively Killed by Pharmacologically-dosed Ascorbic Acid

Ascorbic Acid in Colon Cancer: From the Basic to the Clinical Applications

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