Hepatocellular carcinoma: Updates in primary prevention

Fecht, Will J.; Befeler, Alex S.

doi:10.1007/s11894-004-0024-3

Cited by 9 publications

(5 citation statements)

References 48 publications

(55 reference statements)

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“…Evidence also exists for the progression of breast tumor to the metastatic state and is an important etiologic factor [ 51 ]. Carcinoma of hepatic cells is often associated with chronic infection by hepatitis B or C viruses or ingestion of aflatoxins [ 52 - 56 ]. Oxidative stress induced by these viruses represents one of the intracellular events that cause the genesis of hepatocellular carcinoma [ 17 , 57 ].…”

Section: Oxidative Dna Damage and Cancermentioning

confidence: 99%

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Waris¹,

Ahsan²

2006

J Carcinog

1,150

427

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Oxygen derived species such as superoxide radical, hydrogen peroxide, singlet oxygen and hydroxyl radical are well known to be cytotoxic and have been implicated in the etiology of a wide array of human diseases, including cancer. Various carcinogens may also partly exert their effect by generating reactive oxygen species (ROS) during their metabolism. Oxidative damage to cellular DNA can lead to mutations and may, therefore, play an important role in the initiation and progression of multistage carcinogenesis. The changes in DNA such as base modification, rearrangement of DNA sequence, miscoding of DNA lesion, gene duplication and the activation of oncogenes may be involved in the initiation of various cancers. Elevated levels of ROS and down regulation of ROS scavengers and antioxidant enzymes are associated with various human diseases including various cancers. ROS are also implicated in diabtes and neurodegenerative diseases. ROS influences central cellular processes such as proliferation a, apoptosis, senescence which are implicated in the development of cancer. Understanding the role of ROS as key mediators in signaling cascades may provide various opportunities for pharmacological intervention.

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Section: Oxidative Dna Damage and Cancermentioning

confidence: 99%

Untitled

Waris¹,

Ahsan²

2006

J Carcinog

1,150

427

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“…H epatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide, 1 and the incidence of HCC in developed countries is still increasing as a result of a growing number of carriers of chronic hepatitis C virus infection. 2 The therapeutic options for advanced-stage HCC are limited, and this cancer responds poorly to systemic treatment with chemotherapy.…”

mentioning

confidence: 99%

Telomerase antagonists GRN163 and GRN163L inhibit tumor growth and increase chemosensitivity of human hepatoma

et al. 2005

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Most cancer cells have an immortal growth capacity as a consequence of telomerase reactivation. Inhibition of this enzyme leads to increased telomere dysfunction, which limits the proliferative capacity of tumor cells; thus, telomerase inhibition represents a potentially safe and universal target for cancer treatment. We evaluated the potential of two thio-phosphoramidate oligonucleotide inhibitors of telomerase, GRN163 and GRN163L, as drug candidates for the treatment of human hepatoma. GRN163 and GRN163L were tested in preclinical studies using systemic administration to treat flank xenografts of different human hepatoma cell lines (Hep3B and Huh7) in nude mice. The studies showed that both GRN163 and GRN163L inhibited telomerase activity and tumor cell growth in a dose-dependent manner in vitro and in vivo. The potency and efficacy of the lipid-conjugated antagonist, GRN163L, was superior to the nonlipidated parent compound, GRN163. Impaired tumor growth in vivo was associated with critical telomere shortening, induction of telomere dysfunction, reduced rate of cell proliferation, and increased apoptosis in the treatment groups. In vitro, GRN163L administration led to higher prevalence of chromosomal telomere-free ends and DNA damage foci in both hepatoma cell lines. In addition, in vitro chemosensitivity assay showed that pretreatment with GRN163L increased doxorubicin sensitivity of Hep3B. In conclusion, our data support the development of GRN163L, a novel lipidated conjugate of the telomerase inhibitor GRN163, for systemic treatment of human hepatoma. In addition to limiting the proliferative capacity of hepatoma, GRN163L might also increase the sensitivity of this tumor type to conventional chemotherapy. Similar to other malignant human tumor types, 4 over 80% of human HCC biopsies show activation of telomerase. 5 In contrast, most somatic human tissues, including normal liver, 6 show no or very low levels of telomerase activity. The main function of telomerase is the de novo synthesis of telomeres, which cap the chromosome ends of eukaryotic cells and protect chromosome ends from fusion and DNA damage recognition. 7 Because of the "end replication problem" of DNA polymerase, telomeres shorten during each cell division by 50 to 100 bp. 8 Telomere shortening to a critical length and/or the uncapping of the telomere limit the growth of primary human cells to a finite number of cell divisions, leading to either replicative senescence or crisis. 9-11 A critically short telomere

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“…HCC is one of the most common malignancies, responsible for an estimated one million deaths annually. [ 19 ] Therefore, it becomes important to discover new agents which are effective on growth inhibition of HCC. Taking this into consideration, the present study was conducted on HepG2 cell lines.…”

Section: Discussionmentioning

confidence: 99%

Cytotoxic potential of few Indian fruit peels through 3-(4,5-dimethylthiazol-yl)-2,5-diphenyltetrazolium bromide assay on HepG2 cells

2016

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Objective:To investigate in vitro anticancer activity of a few Indian fruit peels through 3-(4,5-dimethylthiazol-yl)-2,5-diphenyltetrazolium bromide (MTT) assay against HepG2 cells.Materials and Methods:Hydroalcoholic extracts were prepared of five fruit peels, i.e., banana, lemon, guava, orange, and papaya by maceration and thereafter subjected for MTT assay to evaluate anticancer potential on HepG2 cells. Plant extract showed best activity was further fractionated with petroleum ether, chloroform, and ethyl acetate successively and screened again. Phytochemical analysis was then carried out to find out responsible components for the observed activity.Results:Out of the 40 samples from five fruit peel extracts with rich folklore usage, papaya extract showed maximum activity with least inhibitory concentration50 (IC50) value of 18.5 μg/ml. Further analysis after fractionation of the papaya peel extract, aqueous fraction showed the maximum inhibitory activity with least IC50 value of 17.3 μg/ml. Phytochemical analysis of the aqueous fraction of papaya peel extract revealed the presence of flavonoids and glycosides. Total flavonoid content found to be 72.25 mg/g.Conclusion:Papaya fruit extract demonstrated the best activity against MTT assay which may be due to the presence of flavonoids.

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Hepatocellular carcinoma: Updates in primary prevention

Cited by 9 publications

References 48 publications

Untitled

Untitled

Telomerase antagonists GRN163 and GRN163L inhibit tumor growth and increase chemosensitivity of human hepatoma

Cytotoxic potential of few Indian fruit peels through 3-(4,5-dimethylthiazol-yl)-2,5-diphenyltetrazolium bromide assay on HepG2 cells

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