Cytotoxic Effect of Bromelain on HepG2 Hepatocellular Carcinoma Cell Line

Appl Biochem Biotechnol. 2021 Jun;193(6):1873-1897. doi: 10.1007/s12010-021-03505-z. Epub 2021 Mar 18.


Cancer is a complicated long-term disease due to computable key molecular players involved in aggravating the disease. Among various kinds of cancer, hepatocellular carcinoma (HCC) is the ninth leading cause of cancer. Recently, plant-based products are gaining a lot of attention in the field of research because of their anti-tumor properties. In our previous study, we reported based on in-silico method that bromelain, a cysteine protease extracted from the stem of the pineapple, has high binding affinity with the transcription factors p53 and β-catenin proteins which are key players in controlling the progression of hepatocellular carcinoma. Bromelain, isolated mainly from the stem of Pineapple (Ananas comosus), belongs to the family Bromeliaceae. The present study deals with preclinical analysis of bromelain as an anti-cancer agent and its intracellular effect on the expression of p53 and β-catenin protein. Our study reports cytotoxic activity, cell proliferation, migration, invasion, arrest in the S-phase, and G2/M phase in cell cycle analysis by treating with bromelain in HepG2 cell lines. We also report up-regulation of p53 protein by drug-induced impediment leading to apoptotic process in HepG2 cells and down-regulation of β-catenin protein in HepG2 cells which interferes in β-catenin/TCF-DNA interaction further, down-regulating Wnt genes and suppressing the canonical pathway. Finally, we conclude that bromelain inhibits tumorigenic potential in HepG2 cell lines.

Keywords: Anti-cancer; Bromelain; HepG2 cell lines; p53 and beta-catenin.

MeSH terms

  • Ananas / chemistry*
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Bromelains / chemistry
  • Bromelains / pharmacology*
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Cycle / drug effects
  • Cytotoxins / chemistry
  • Cytotoxins / pharmacology*
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Neoplasm Invasiveness
  • Tumor Suppressor Protein p53 / metabolism
  • beta Catenin / metabolism


  • Antineoplastic Agents, Phytogenic
  • CTNNB1 protein, human
  • Cytotoxins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • beta Catenin
  • Bromelains