Bacterial cupredoxin azurin as an inducer of apoptosis and regression in human breast cancer

Vasu Punj, Suchita Bhattacharyya, Djenann Saint-Dic, Chenthamarakshan Vasu, Elizabeth A. Cunningham, Jewell Graves, Tohru Yamada, Andreas I. Constantinou, Konstantin Christov, Bethany White, Gang Li, Dibyen Majumdar, Ananda M. Chakrabarty, Tapas K. Das Gupta*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

104 Scopus citations

Abstract

Azurin, a copper-containing redox protein released by the pathogenic bacterium Pseudomonas aeruginosa, is highly cytotoxic to the human breast cancer cell line MCF-7, but is less cytotoxic toward p53-negative (MDA-MB-157) or nonfunctional p53 cell lines like MDD2 and MDA-MB-231. The purpose of this study was to investigate the underlying mechanism of the action of bacterial cupredoxin azurin in the regression of breast cancer and its potential chemotherapeutic efficacy. Azurin enters into the cytosol of MCF-7 cells and travels to the nucleus, enhancing the intracellular levels of p53 and Bax, thereby triggering the release of mitochondrial cytochrome c into the cytosol. This process activates the caspase cascade (including caspase-9 and caspase-7), thereby initiating the apoptotic process. Our results indicate that azurin-induced cell death stimuli are amplified in the presence of p53. In vivo injection of azurin in immunodeficient mice harboring xenografted human breast cancer cells in the mammary fat pad leads to statistically significant regression (85%, P = 0.0179, Kruskal-Wallis Test) of the tumor. In conclusion, azurin blocks breast cancer cell proliferation and induces apoptosis through the mitochondrial pathway both in vitro and in vivo, thereby suggesting a potential chemotherapeutic application of this bacterial cupredoxin for the treatment of breast cancer.

Original languageEnglish (US)
Pages (from-to)2367-2378
Number of pages12
JournalOncogene
Volume23
Issue number13
DOIs
StatePublished - Mar 25 2004

Keywords

  • Apoptosis
  • Breast cancer
  • Cupredoxin azurin

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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