Hepatoblastoma: A Need for Cell Lines and Tissue Banks to Develop Targeted Drug Therapies

Rikhi, Rishi; Spady, Kimberlee K.; Hoffman, Ruth I.; Bateman, Michael S.; Bateman, Max; Howard, Lisa

doi:10.3389/fped.2016.00022

Cited by 31 publications

(32 citation statements)

References 44 publications

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“…The TET enzymes are comprised of three members: TET1, TET2 and TET3 ( 26 ). The expression of TET1, TET2 and TET3 was assessed using RT-qPCR of HepG2 cells cultured under 21, 5 or 1% oxygen for 24 h. The HepG2 cell line is one of the most utilized cell lines in in vitro studies on HB, since it is well characterized and retains numerous hepatocyte-associated features ( 33 , 34 ). As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…HepG2 cells were isolated from a human liver biopsy of a 15-year old male with HB, and were originally considered to be a HCC cell line, but were later shown to be a HB cell line ( 39 – 41 ). This cell line is widely utilized in vitro to study HB due to preserving numerous hepatocyte-associated features ( 33 , 34 ). The present study demonstrates that three TET enzyme family members, namely TET1, TET2 and TET3, are expressed in HepG2 cells and are involved in maintaining the balance of DNA methylation.…”

Section: Discussionmentioning

confidence: 99%

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Hypoxia induces the expression of TET enzymes in HepG2 cells

et al. 2017

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Hypoxia promotes tumor malignancy in solid tumors. One key mechanism by which this occurs is via epigenetic alteration. The present study demonstrates that hypoxia upregulates the expression of the ten-eleven-translocation 5-methylcytosine dioxygenase (TET) enzymes, which catalyze the conversion of 5-methylcytosine to 5-hydroxymethylcytosine (5-hmC), thereby leading to elevated cellular 5-hmC levels in hepatoblastoma HepG2 cells. Hypoxia inducible factor-1α (HIF-1α) is the main transcription factor activated by hypoxia. A chemical inducer of HIF-1α, CoCl2, also increases the expression of TET enzymes. Knockdown of HIF-1α attenuates the hypoxia-induced expression of TET enzymes. These results indicate that hypoxia controls DNA methylation through HIF-1α-mediated TET enzyme regulation in HepG2 cells.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Hypoxia induces the expression of TET enzymes in HepG2 cells

et al. 2017

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“…Fifteen types of hepatoblastoma cell lines are sold throughout the world [21]. However, only the HUH-6 hepatoblastoma cell line is available in Japan.…”

Section: Discussionmentioning

confidence: 99%

Arctigenin induces apoptosis in human hepatoblastoma cells

et al. 2019

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Purpose Arctigenin has been shown to have anti-tumor effects in various types of cancers. This study was conducted to verify these effects in the human-derived hepatoblastoma cell line, HUH-6 clone 5 (hereinafter, HUH-6). Methods Arctigenin was added to cultured HUH-6 cells, and cellular activity was evaluated by MTS assay. To determine the relationship between reduced cellular activity and apoptosis, we measured the activities of caspase 3/7, 8, and 9 and conducted flow cytometry with Annexin V/PI staining. Results The MTS assay revealed that cellular activity decreased after arctigenin treatment in a concentration-dependent manner (IC 50 = 4 µM). To investigate apoptosis induction, activity assays of caspase 3/7, 8, and 9 were performed. While caspase 3/7 and 8 exhibited high activity, caspase 9 showed no activity. Thus, apoptosis induction may have involved the action of tumor necrosis factor receptor 1 (TNFR1). Flow cytometry conducted with Annexin V/PI staining revealed the occurrence of early apoptosis. Conclusion We found that arctigenin has anti-tumor effects in HUH-6 cells in a concentration-dependent manner. Arctigenin may have exerted its anti-tumor effect by inducing apoptosis via TNFR1, which recruits Complex IIa to activate caspase 8 and 3/7. These results may be useful for developing therapeutic agents for hepatoblastoma.

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“…The aggressive nature of high-risk HB concomitant with the relatively low overall disease incidence has historically prevented substantial study of more effective chemotherapy regimens and targeted therapies due to the lack of available samples. Only three cell lines, HepG2, Huh-6, and HepT1, are widely available for laboratory studies [13][14][15][16]. Relevant animal models have been developed more recently as a response to this historical difficulty, allowing researchers to accurately recapitulate human tumors in murine models to further study tumor biology and new treatment algorithms in an effort to increase overall survival of patients with high-risk disease.…”

Section: Introductionmentioning

confidence: 99%

Animal Modeling of Pediatric Liver Cancer

Whitlock

Yang

Vasudevan

et al. 2020

Cancers

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Hepatoblastoma (HB) is the most common pediatric liver malignancy. Management of HB requires multidisciplinary efforts. The 5-year overall survival of this disease is about 80% in developed countries. Despite advances in the care of these patients, survival in recurrent or treatment-refractory disease is lower than 50%. This is due to more complex tumor biology, including hepatocellular carcinoma (HCC)-like mutations and expression of aggressive gene signatures leading to chemoresistance, vascular invasion, and metastatic spread. The current treatment protocols for pediatric liver cancer do not incorporate targeted therapies, and the ability to test these therapies is limited due to the inaccessibility of cell lines and mouse models. In this review, we discuss the current status of preclinical animal modeling in pediatric liver cancer, primarily HB. Although HB is a rare cancer, the research community has worked together to develop a range of interesting and relevant mouse models for diverse preclinical studies.

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Hepatoblastoma: A Need for Cell Lines and Tissue Banks to Develop Targeted Drug Therapies

Cited by 31 publications

References 44 publications

Hypoxia induces the expression of TET enzymes in HepG2 cells

Hypoxia induces the expression of TET enzymes in HepG2 cells

Arctigenin induces apoptosis in human hepatoblastoma cells

Animal Modeling of Pediatric Liver Cancer

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