Genotoxicity of irinotecan and its modulation by vitamins A, C and E in human lymphocytes from healthy individuals and cancer patients

Kontek, Renata; Drozda, Rafał; Sliwinski, Marcin; Grzegorczyk, Krzysztof

doi:10.1016/j.tiv.2009.10.013

Cited by 19 publications

(8 citation statements)

References 39 publications

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“…Gol'dberg et al (2008) described that glycyrrhizic acid extracted from licorice root, which has as an anti-inflammatory and immunomodulatory substance, improves the efficacy of cytostatic therapies such as cyclophosphamide that inhibits the growth and development of metastasis in lung tumor (3). Also, the slowdown of the disease progression has been observed after the addition of certain vitamins to the diet of patients undergoing chemotherapy (4). In fact, some authors have described that melatonin and vitamin C and E decrease the extent of DNA lesions on human lymphocytes and gastric mucosa after infection with Helicobacter pylori (4,5).…”

Section: Introductionmentioning

confidence: 99%

“…Also, the slowdown of the disease progression has been observed after the addition of certain vitamins to the diet of patients undergoing chemotherapy (4). In fact, some authors have described that melatonin and vitamin C and E decrease the extent of DNA lesions on human lymphocytes and gastric mucosa after infection with Helicobacter pylori (4,5). …”

Section: Introductionmentioning

confidence: 99%

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Ocoxin oral solution® as a complement to irinotecan chemotherapy in the metastatic progression of colorectal cancer to the liver

et al. 2017

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Colorectal cancer (CRC) is an aggressive disease in which patients usually die due to its metastatic progression to the liver. Up to date, irinotecan is one of the most used chemotherapeutic agents to treat CRC metastasis with demonstrated efficacy. However, the severity of the side effects constitute the main limitation to its use in the treatment. Consequently, new complementary therapies are being developed to avoid these adverse effects while maintaining the efficacy of the antitumoral drugs. Ocoxin oral solution (OOS®) is a nutritional mixture containing biologically active compounds with demonstrated antitumoral and immunomodulatory effects. Thus, we aimed to analyze the effect of OOS® as a suitable complement to irinotecan therapy in the treatment of CRC metastasis to the liver. First, the effect of OOS®, irinotecan and the combination of both on the viability of C26 cells was tested in vitro and in vivo. Second, the expression of caspase-3, Ki67 and the macrophage infiltration by F4/80 marker was quantified in liver tissue sections by immunohistochemistry. Finally, mRNA microarray study was carried out on tumor cells isolated from tumor-bearing livers collected from mice subjected to the above treatments. Our results show that OOS® administered as a complementary therapy to irinotecan reduced tumor cell viability in vitro. Moreover, irinotecan administered either alone or in combination with 100 µl OOS® from the 7th day after tumor cell inoculation decreased the metastatic growth in the liver. Besides, several genes with binding and catalytic activities showed to be deregulated by RNA microarray analysis. In conclusion, OOS®, when administered as a complement to irinotecan, reduced the metastatic development of colorectal cancer to the liver. Additionally, the overall health state of the animals improved. These results point out OOS® as a potential supplement to the anti-tumoral treatments used in clinical settings in patients suffering from disseminated colorectal cancer.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ocoxin oral solution® as a complement to irinotecan chemotherapy in the metastatic progression of colorectal cancer to the liver

et al. 2017

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“…Single cell gel electrophoresis (SCGE, comet assay) is a sensitive technique for detection the level of DNA damage. The SCGE was performed under alkaline conditions (pH > 13), according to the procedure of Singh et al [60] with some modifications as described previously [61]. This version is capable to detect DNA single-strand breaks (SSB), double-strand breaks (DSB), alkali labile sites (ALS), oxidative base damage, and crosslinks with DNA induced by genotoxic agents [62].…”

Section: Dna Damage-alkaline Comet Assaymentioning

confidence: 99%

Antagonistic Effects of CAPE (a Component of Propolis) on the Cytotoxicity and Genotoxicity of Irinotecan and SN38 in Human Gastrointestinal Cancer Cells In Vitro

et al. 2020

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The incidence of gastrointestinal cancers is increasing every year. Irinotecan (CPT-11), a drug used in the treatment of colorectal cancer and gastric cancer, is metabolized by carboxylesterases to an active metabolite, SN-38, which is more cytotoxic. CAPE (caffeic acid phenethyl ester) is an active component of propolis, which has a high antibacterial, antiviral, and antineoplastic potential. This study analyses the impact of CAPE on the cytotoxic (MTT assay), genotoxic (comet assay) and proapoptotic (caspase-3/7 activity) potential of irinotecan and its metabolite SN-38 in cultures of gastrointestinal neoplastic cells (HCT116, HT29, AGS). Cytotoxicity and genotoxicity activities of these compounds were carried out in comparison with human peripheral blood lymphocytes (PBLs) in vitro. The antioxidant potential of CAPE was investigated in relation H2O2-induced oxidative stress in the both neoplastic cells and PBLs. CAPE expressed cytotoxic, genotoxic, and pro-apoptotic activity against AGS, HCT116, and HT29 tumor cells. CAPE, in the presence of different concentrations of irinotecan or SN38, decreased the cytotoxicity, genotoxicity, and pro-apoptotic activity in these cell lines, but it has no such action on normal human peripheral blood lymphocytes.

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“…Since ROS are constitutively For instance, although vitamin C and other hydrophobic polyphenolic compounds possess strong antioxidant and anti-genotoxic activities against specific ROS in vitro (Noroozi et al, 1998;Kontek et al, 2010), human trials have often failed to demonstrate preventive effects on DNA oxidation (Retana-Ugalde et al, 2008). Furthermore, methods for evaluating antioxidant activity in naturally occurring substances…”

Section: Introductionmentioning

confidence: 99%

“…Accordingly, standard methods for measuring antioxidant activity in foods have been devised using artificial ROS, leading to informed recommendations for daily antioxidant intake (Aruoma et al, 2003;Prior et al, 2005). However, only a few studies have directly indicated that antioxidants reduce the risk of chronic and degenerative diseases.*To whom correspondence should be addressed.E-mail: nyanai@affrc.go.jp N. Yanai et al 486 For instance, although vitamin C and other hydrophobic polyphenolic compounds possess strong antioxidant and anti-genotoxic activities against specific ROS in vitro (Noroozi et al, 1998;Kontek et al, 2010), human trials have often failed to demonstrate preventive effects on DNA oxidation (Retana-Ugalde et al, 2008). Furthermore, methods for evaluating antioxidant activity in naturally occurring substances…”

mentioning

confidence: 99%

A Mixture of Histidine-Dipeptides, Vitamin C, and Ferulic Acid Reduces Comet Assay Scores in Normal Middle-Aged Men.

Yanai

Niitsuma

Shiotani

et al. 2014

FSTR

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Specific antioxidants have previously been found to target particular reactive oxygen species. For example, histidine-dipeptides neutralize hypochlorite, while ascorbic acid targets peroxynitrite and ferulic acid scavenges hydroxyl radicals. In this study, we investigated the effects of a mixture of these antioxidants on oxidative stress in middle-aged men. Seventeen male volunteers ingested an antioxidant mixture containing histidine-dipeptides, vitamin C, and ferulic acid for 8 weeks. DNA damage in peripheral leukocytes was measured at 4-week intervals using comet assays. For comparison, oxidative status in twelve normal volunteers who did not ingest the test drink (control group) were examined. DNA damage was remarkably reduced at the 8-and 12-week follow-ups. Plasma LDL-cholesterol levels were also reduced at 8 weeks. In contrast, notable changes in DNA damage were not observed in the control group. In addition, the antioxidant mixture administered in this trial did not produce toxic effects on the liver, kidney, or pancreatic function. Thus, such antioxidant combinations may contribute to the maintenance of health in middleaged men.Keywords: histidine-dipeptides, vitamin C, ferulic acid, antioxidant combination, comet assay, reactive oxygen species (ROS) IntroductionAging and chronic disease involve cellular apoptosis, which is promoted by reactive oxygen species (ROS) (Harman, 1972;Richter et al., 1995;Johnson et al., 1996). Since ROS are constitutively generated from energy metabolism and immune processes (Marnett, 2003), antioxidants and enzymes play important roles in preventing aging and in the progression of chronic diseases such as hypertension, diabetes, other cardiovascular diseases, and cancer. Endogenous antioxidants, ubiquinones such as Coenzyme Q10 (CoQ10), and antioxidant enzymes, such as superoxide dismutase (SOD), glutathione peroxidase, and catalase, are all involved in mitochondrial and cytoplasmic defense systems and act to neutralize a variety of ROS (Chaudière et al., 1999;Powers et al., 1999;Curtin et al., 2002). Therefore, ingestion of sufficient quantities of naturally occurring antioxidants from the diet and supplements is also considered to be very important for suppressing the aging progress and ameliorating the risk of ROS-mediated chronic diseases. Accordingly, standard methods for measuring antioxidant activity in foods have been devised using artificial ROS, leading to informed recommendations for daily antioxidant intake (Aruoma et al., 2003;Prior et al., 2005). However, only a few studies have directly indicated that antioxidants reduce the risk of chronic and degenerative diseases.*To whom correspondence should be addressed.E-mail: nyanai@affrc.go.jp N. Yanai et al. 486 For instance, although vitamin C and other hydrophobic polyphenolic compounds possess strong antioxidant and anti-genotoxic activities against specific ROS in vitro (Noroozi et al., 1998;Kontek et al., 2010), human trials have often failed to demonstrate preventive effects on DNA oxidation (Retana-Ugalde...

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Genotoxicity of irinotecan and its modulation by vitamins A, C and E in human lymphocytes from healthy individuals and cancer patients

Cited by 19 publications

References 39 publications

Ocoxin oral solution® as a complement to irinotecan chemotherapy in the metastatic progression of colorectal cancer to the liver

Ocoxin oral solution® as a complement to irinotecan chemotherapy in the metastatic progression of colorectal cancer to the liver

Antagonistic Effects of CAPE (a Component of Propolis) on the Cytotoxicity and Genotoxicity of Irinotecan and SN38 in Human Gastrointestinal Cancer Cells In Vitro

A Mixture of Histidine-Dipeptides, Vitamin C, and Ferulic Acid Reduces Comet Assay Scores in Normal Middle-Aged Men.

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