Synergistic potentiation of interferon activity with maitake mushroom d-fraction on bladder cancer cells.
OBJECTIVE
To examine whether the combination of interferon (IFN)-alpha and maitake mushroom D-fraction (PDF), a bioactive mushroom extract, might potentiate the anticancer activity of IFN-alpha in bladder cancer T24 cells in vitro.


METHODS
Effects of recombinant IFN-alpha(2b) (0-50 000 IU/mL), PDF (0-700 microg/mL), or their combinations were assessed on T24 cell growth at 72 h. Cell cycle analysis and assays for double-stranded DNA-dependent protein kinase (DNA-PK) were performed to explore possible antiproliferative mechanism of these agents.


RESULTS
IFN-alpha(2b) was able to induce a significant ( approximately 50%) growth reduction at 20 000 IU/mL, which further declined to approximately 66% at 50 000 IU/mL. PDF had no effects up to 200 microg/mL, but there was an approximately 20% and approximately 53% growth reduction at 400 and 700 microg/mL, respectively. When the varying concentrations of IFN-alpha(2b) and PDF were combined, 10 000 IU/mL of IFN-alpha(2b) combined with 200 microg/mL of PDF resulted in an approximately 75% growth reduction. This was accompanied by a G(1) cell cycle arrest, shown by cell cycle analysis. Concurrently, DNA-PK activity in IFN-alpha(2b)/PDF-treated cells was almost three-fold higher than controls.


CONCLUSIONS
The combination of IFN-alpha(2b) (10 000 IU/mL) and PDF (200 microg/mL) reduced growth by approximately 75% in T24 cells. This appears to be due to a synergistic potentiation of these two agents, inducing a G(1) arrest with DNA-PK activation. Therefore, the IFN-alpha(2b)/PDF combination could trigger DNA-PK activation that may act on the cell cycle to cease cancer cell growth.
Louie
Brandon
B
Department of Urology, New York Medical College, Valhalla, NY, USA.
Rajamahanty
Srinivas
S
Won
John
J
Choudhury
Muhammad
M
Konno
Sensuke
S
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004357:Drug Synergism; D048691:Grifola; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents; D016898:Interferon-alpha