Bacterial cupredoxin azurin as an inducer of apoptosis and regression in human breast cancer.
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.
Punj
Vasu
V
Department of Surgical Oncology, University of Illinois at Chicago, 840 South Wood Street, M/C 820, Chicago, IL 60612, USA.
Bhattacharyya
Suchita
S
Saint-Dic
Djenann
D
Vasu
Chenthamarakshan
C
Cunningham
Elizabeth A
EA
Graves
Jewell
J
Yamada
Tohru
T
Constantinou
Andreas I
AI
Christov
Konstantin
K
White
Bethany
B
Li
Gang
G
Majumdar
Dibyen
D
Chakrabarty
Ananda M
AM
Das Gupta
Tapas K
TK
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001400:Azurin / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D005260:Female; D006801:Humans; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000970:Antineoplastic Agents; D016159:Tumor Suppressor Protein p53; D001400:Azurin; D020169:Caspases