TITLE:
Eosinophil MBP Extract Modulates Oncogene Expression in Prostate Tumor Cells: A Preliminary Study with Monolayer Cultures
AUTHORS:
Christine A. Clarke, Michael A. Smith, Ibrahim Laniyan, Theresa R. Vaughn, Debra Parish-Gause, William Green, Paulette M. Furbert-Harris
KEYWORDS:
Eosinophils, Major Basic Protein (MBP), Prostate Cancer, HPC8L, Oncogenes
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.6 No.6,
May
29,
2015
ABSTRACT: Prostate cancer is the second leading
cause of cancer deaths in the United States and remains a significant health
concern for men throughout the world. Despite the discovery of promising
immunotherapeutic strategies, curative outcomes remain elusive. We have
investigated eosinophils as potential anti-cancer effector cells, and have
reported the ability of their toxic granular proteins (MBP, EPO, ECP, EDN) to
inhibit prostate tumor cell growthin
vitro. This study investigates the effect of eosinophil MBP extract on the
expression of oncogenes p53, bcl-xl, bax, and c-myc, which modulate tumor
growth, proliferation, and apoptosis. Briefly, granular proteins were
differentially extracted from GRC.014.22 and GRC.014.24, eosinophilic cell
lines established in our laboratory from a patient with moderate asthma.
Protein extracts were fractionated on Sephadex G-50 columns, and prostate tumor
cell lines DU-145, LNCaP, PC-3, and HPC8L (established in our laboratory from a
tumor resected from an African American patient) were treated with MBP extracts
from the pooled third peaks. Colony formation and monolayer cell growth
inhibition assays were used to evaluate the protein’s growth inhibitory
activity against prostate tumor cells; and gene expression analyses, to
determine p53, bcl-xl, bax, and c-myc oncogene expression. We show that the
granular proteins were potent in their action on HPC8L, inhibiting colony
formation in a dose-dependent manner. Treated prostate tumor cell lines trended
toward apoptosis-induction, as evident in bcl-xl/bax ratios