Lycopene treatment stalls the onset of experimentally induced hepatocellular carcinoma: a radioisotopic, physiological and biochemical analysis

Bhatia, Nisha; Singh, Baljinder; Koul, Ashwani

doi:10.20517/2394-5079.2018.04

Cited by 9 publications

(10 citation statements)

References 44 publications

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“…After removing duplicates (n=98), 188 records were screened using titles and abstracts of which 38 studies retained for the full-text review. Finally, a total of 15 studies were included in the systematic review ( Watanabe et al, 2001 ; Toledo et al, 2003 ; Takahashi et al, 2010 ; Wang et al, 2010 ; Gupta et al, 2013a ; Gupta et al, 2013b ; Gupta et al, 2013c ; Ip et al, 2013 ; Ip et al, 2014 ; Sahin et al, 2014 ; Bhatia et al, 2015 ; Stice et al, 2015 ; Aizawa et al, 2016 ; Gupta et al, 2016 ; Bhatia et al, 2018 ), of which 10 studies ( Watanabe et al, 2001 ; Toledo et al, 2003 ; Takahashi et al, 2010 ; Wang et al, 2010 ; Gupta et al, 2013c ; Ip et al, 2013 ; Ip et al, 2014 ; Sahin et al, 2014 ; Stice et al, 2015 ; Aizawa et al, 2016 ) included in the meta-analysis. The major reasons for exclusion were not containing the outcome of interest (n=9), not related to exposure of interest, and being in vitro study (n=5) ( Figure 1 ).…”

Section: Resultsmentioning

confidence: 99%

“…More than 1/3 of the studies used BALB/c mice ( Gupta et al, 2013a ; Gupta et al, 2013b ; Gupta et al, 2013c ; Bhatia et al, 2015 ; Gupta et al, 2016 ; Bhatia et al, 2018 ) and others used Wistar rats ( Toledo et al, 2003 ; Sahin et al, 2014 ; Stice et al, 2015 ), Sprague-Dawley rats ( Wang et al, 2010 ), WT/BCO2-KO mice ( Ip et al, 2014 ), C3H/HeN mice ( Takahashi et al, 2010 ), C57BL/6J mice ( Ip et al, 2013 ), ferrets ( Aizawa et al, 2016 ), and Long-Evans Cinnamon rats ( Watanabe et al, 2001 ). Six of the 15 studies enrolled female animals ( Gupta et al, 2013a ; Gupta et al, 2013b ; Gupta et al, 2013c ; Bhatia et al, 2015 ; Gupta et al, 2016 ; Bhatia et al, 2018 ). Although more than half of the studies used 5 mg/kg dose and given before administration of the carcinogen, there was significant variation among studies in terms of dose, frequency, and duration of lycopene administration.…”

Section: Resultsmentioning

confidence: 99%

“…For instance, in studies conducted using hepatoma cell lines lycopene inhibited cell growth, migration, and invasion ( Huang et al, 2008 ; Yang et al, 2012 ; Jhou et al, 2017 ). Besides, orally administered lycopene attenuates liver-specific carcinogen diethylnitrosamine (DEN)-induced hepatocarcinogenesis in rodents ( Ip et al, 2014 ; Sahin et al, 2014 ; Bhatia et al, 2018 ). To our knowledge, no published systematic review or meta-analysis that reported evidence vis-à-vis the effects of lycopene in animal models of HCC.…”

Section: Introductionmentioning

confidence: 99%

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Anti-Cancer Effects of Lycopene in Animal Models of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

et al. 2020

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Introduction: Globally, hepatocellular carcinoma (HCC) is the sixth most diagnosed cancer and the third important cause of cancer-related death. As there are only two targeted drugs for the treatment of advanced HCC-that merely extend survival by a few months-the need for alternative treatments is inevitable. Lycopene, a carotenoid that is known to be most abundant in red tomatoes and tomato-based products, has been investigated for its anticancer activity in various types of cancers including HCC. This review was conducted to evaluate the effects of lycopene on HCC from animal models to pave the way for further clinical studies. Methods: Electronic databases and search engines including PubMed, EMBASE, and Google Scholar were searched for original records addressing the anticancer effect of lycopene in animal models of HCC. Data were extracted using a format prepared in Microsoft Excel and exported to Stata 15.0 for analyses. A meta-analysis was performed using a random-effects model at a 95% confidence level for the outcome measures: tumor incidence, number, and growth (tumor volume and size). The presence of publication bias between studies was evaluated using Egger's test and funnel plot. The study protocol was registered in the PROSPERO database with reference number: CRD42019159312. Results: The initial database search yields 286 articles, of which 15 studies met the inclusion criteria. The characteristics of the included studies were a bit diversified. The studies involved a total of 644 animals (312 treatment and 332 control groups) and mice shared the majority (488) followed by rats (117) and ferrets (39). The meta-analysis showed that lycopene significantly reduced the incidence [RR 0.8; 95% CI 0.69, 0.92 (p=0.00); I 2 = 30.4%, p=0.16; n=11], number [SMD-1.83; 95% CI-3.10,-0.57 (p=0.01); I 2 = 95.9%, p=0.00; n=9], and growth [SMD-2.13; 95% CI-4.20,-0.04 (p=0.04); I 2 = 94.6%, p=0.00; n=4] of HCC.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Anti-Cancer Effects of Lycopene in Animal Models of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

et al. 2020

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“… 53 , 93 , 96 , 107 Besides, lycopene promoted the pro-apoptotic genes expression including caspase 3, 9 and p53 108 , modulated cellular proliferation, glycolysis and attenuated the oxidation stress and inflammation. 109 , 110 Indeed, experimental studies provided evidence that lycopene may act as an anti-inflammatory agent against certain types of disease, including those of the liver, lung, colon and prostate. 98 , 111 , 112 Patients with fatty liver have significantly reduced plasma lycopene.…”

Section: Dietary Tomato Rich In Lycopene Inhibits Ald By Suppressing mentioning

confidence: 99%

“…Lycopene is the most well-known for its potent antioxidant potential and also possesses many other bioactive abilities including modulation of intercellular gap junction communication, hormonal and immune systems, metabolic pathways, induction of phase II detoxification enzymes, and regulation of gene function 53, 93, 96, 107. Besides, lycopene promoted the pro-apoptotic genes expression including caspase 3, 9 and p53 108 , modulated cellular proliferation, glycolysis and attenuated the oxidation stress and inflammation 109, 110. Indeed, experimental studies provided evidence that lycopene may act as an anti-inflammatory agent against certain types of disease, including those of the liver, lung, colon and prostate 98, 111, 112.…”

Section: Dietary Tomato Rich In Lycopene Inhibits Ald By Suppressing mentioning

confidence: 99%

Tomato lycopene prevention of alcoholic fatty liver disease and hepatocellular carcinoma development

Stice

Xia

Wang

2018

Chronic Diseases and Translational Medicine

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Alcoholic liver disease (ALD) is a major cause of morbidity and mortality worldwide. The incidence of hepatocellular carcinoma (HCC) is increasing in the United States, and chronic, excessive alcohol consumption is responsible for 32%–45% of all the liver cancer cases in the United States. Avoidance of chronic or excessive alcohol intake is the best protection against alcohol-related liver injury; however, the social presence and addictive power of alcohol are strong. Induction of the cytochrome P450 2E1 (CYP2E1) enzyme by chronic and excessive alcohol intake is known to play a role in the pathogenesis of ALD. High intake of tomatoes, rich in the carotenoid lycopene, is associated with a decreased risk of chronic disease. The review will overview the prevention of ALD and HCC through dietary tomato rich in lycopene as an effective intervention strategy and the crucial role of CYP2E1 induction as a molecular target. The review also indicates a need for caution among individuals consuming both alcohol and high dose lycopene as a dietary supplement.

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Olsalazine pretreatment augments chemosensitivity of gemcitabine in hepatocellular carcinoma

Sharma,

Chhipa,

Verma

et al. 2024

J Biochem & Molecular Tox

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Recently, olsalazine a DNA hypomethylating agent was found to inhibit the growth of breast cancer cells. The present study was carried out to evaluate the effects of olsalazine pretreatment in the potentiation of chemosensitivity of gemcitabine for the treatment of hepatocellular carcinoma (HCC). In silico molecular docking was performed to analyze the interaction of olsalazine and gemcitabine with DNMT1 and DNA, respectively, using the AutoDock tools 1.5.6. Cytotoxicity of olsalazine, gemcitabine, and combination were measured on human HePG2 cells using MTT assay. Antiproliferative effects were assessed using animal model of N‐nitrosodiethylamine and carbon tetrachloride‐induced HCC. Treatment was initiated from 8th week of induction to 11th week and change in body weight, liver weight, and survival rate were measured. Following treatment, blood samples were collected for estimation serum biochemistry. Blood serum was used for the estimation of inflammatory cytokines tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6), C‐reactive protein [CRP], lactate dehydrogenase (LDH), and P53 levels. Oxidative stress markers were measured in liver tissue homogenates. Histopathology and immunohistochemistry (IHC) were performed on liver sections to detect the morphological changes and P53 expression. Docking analysis revealed the interactions between olsalazine and DNMT1 with a binding energy score of −5.34 and gemcitabine and DNA with a binding energy score of −5.93. Olsalazine pretreatment potentiated the antiproliferative effect of gemcitabine in cell line study. In the group receiving olsalazine pretreatment showed significant reductions in relative liver weight and improved survival rate of gemcitabine treatment group. Serum biochemical markers: serum glutamate pyruvate transaminase, serum glutamic oxaloacetic transaminase, alkaline phosphatase, and bilirubin revealed improved liver functions. Olsalazine pretreatment also reduced the levels of inflammatory markers like CRP, LDH, TNF‐α, and IL‐6 and oxidative stress markers dose dependently. Histopathology and IHC showed improved liver morphology with potentiated the induction of P53 upon olsalazine pretreatment in combination with gemcitabine. In conclusion, sequential combination of olsalazine and gemcitabine improved the treatment outcomes during the progression of HCC.

show abstract

Lycopene treatment stalls the onset of experimentally induced hepatocellular carcinoma: a radioisotopic, physiological and biochemical analysis

Cited by 9 publications

References 44 publications

Anti-Cancer Effects of Lycopene in Animal Models of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Anti-Cancer Effects of Lycopene in Animal Models of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Tomato lycopene prevention of alcoholic fatty liver disease and hepatocellular carcinoma development

Olsalazine pretreatment augments chemosensitivity of gemcitabine in hepatocellular carcinoma

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