Berberine regulates the protein expression of multiple tumorigenesis-related genes in hepatocellular carcinoma cell lines

Tung Yueh Chuang, Hsiao Li Wu, Jie Min, Michael Peter Diamond, Ricardo Azziz, Yen-Hao Chen

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: Hepatocellular carcinoma (HCC) is the seventh most common malignancy and the third leading cause of cancer-related death worldwide with an extremely grim prognosis. Berberine (BBR) has been found to inhibit proliferation of human HCC cells, although the underlying mechanism(s) are unclear. Methods: Protein expression was detected by Western blots. Cell viability was determined by using the CellTiter Assay kit. Results: We confirm that BBR treatment inhibits HepG2, Hep3B, and SNU-182 cell viability, and suggest that it regulates this proliferation via the modulation of multiple tumorigenesis-related genes protein expression. BBR treatment up-regulated protein expression of tumor suppressor genes, including Kruppel-like factor 6 (KLF6), activating transcription factor 3 (ATF3) and p21, while down-regulating the expression of selected oncogenes, including E2F transcription factor 1 (E2F1) and pituitary tumor transforming gene 1 (PTTG1). The specific extracellular signal-regulated kinases 1/2 (ERK1/2) inhibitor, PD98059, partially inhibited BBR effects including reduction of cell viability, and up-regulation of KLF6 and ATF3 expressions; although, PD98059 did not alter the down-regulation of E2F1 and PTTG1 expression by BBR. Conclusions: Our results suggest that BBR inhibits HCC cell viability by modulating multiple tumorigenesis-related genes, and that up-regulation of tumor suppressor genes by BBR is in part the result of ERK1/2 action. The results of this study augment our understanding of the mechanisms underlying the effect of BBR on hepatocellular cancers and provide further evidence as to the biological plausibility of this agent's role in the treatment of these malignancies.

Original languageEnglish (US)
Article number59
JournalCancer Cell International
Volume17
Issue number1
DOIs
StatePublished - May 30 2017

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Berberine
Hepatocellular Carcinoma
Carcinogenesis
Cell Line
Genes
Cell Survival
Proteins
Activating Transcription Factor 3
E2F1 Transcription Factor
Oncogenes
Kruppel-Like Transcription Factors
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Pituitary Neoplasms
Tumor Suppressor Genes
Up-Regulation
Gene Expression
Neoplasms
Biological Factors
Liver Neoplasms

Keywords

  • ATF3
  • Berberine
  • E2F1
  • ERK1/2
  • Hepatocellular carcinoma
  • KLF6
  • P21
  • PTTG1

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

Cite this

Berberine regulates the protein expression of multiple tumorigenesis-related genes in hepatocellular carcinoma cell lines. / Chuang, Tung Yueh; Wu, Hsiao Li; Min, Jie; Diamond, Michael Peter; Azziz, Ricardo; Chen, Yen-Hao.

In: Cancer Cell International, Vol. 17, No. 1, 59, 30.05.2017.

Research output: Contribution to journalArticle

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abstract = "Background: Hepatocellular carcinoma (HCC) is the seventh most common malignancy and the third leading cause of cancer-related death worldwide with an extremely grim prognosis. Berberine (BBR) has been found to inhibit proliferation of human HCC cells, although the underlying mechanism(s) are unclear. Methods: Protein expression was detected by Western blots. Cell viability was determined by using the CellTiter Assay kit. Results: We confirm that BBR treatment inhibits HepG2, Hep3B, and SNU-182 cell viability, and suggest that it regulates this proliferation via the modulation of multiple tumorigenesis-related genes protein expression. BBR treatment up-regulated protein expression of tumor suppressor genes, including Kruppel-like factor 6 (KLF6), activating transcription factor 3 (ATF3) and p21, while down-regulating the expression of selected oncogenes, including E2F transcription factor 1 (E2F1) and pituitary tumor transforming gene 1 (PTTG1). The specific extracellular signal-regulated kinases 1/2 (ERK1/2) inhibitor, PD98059, partially inhibited BBR effects including reduction of cell viability, and up-regulation of KLF6 and ATF3 expressions; although, PD98059 did not alter the down-regulation of E2F1 and PTTG1 expression by BBR. Conclusions: Our results suggest that BBR inhibits HCC cell viability by modulating multiple tumorigenesis-related genes, and that up-regulation of tumor suppressor genes by BBR is in part the result of ERK1/2 action. The results of this study augment our understanding of the mechanisms underlying the effect of BBR on hepatocellular cancers and provide further evidence as to the biological plausibility of this agent's role in the treatment of these malignancies.",
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