Abstract
Background: Tetracyclines such as doxycycline are reported to possess cytotoxic activity against mammalian tumor cells, but the mechanism of their effects on cell proliferation remains unclear. Materials and Methods: The antitumor effect of doxycycline was investigated in human pancreatic cancer cell line, PANC-1. We also investigated the effect of doxycycline on expression of a potent proangiogenic factor, interleukin (IL)-8. Results: In excess of 20 μg/ml, cytotoxic effects of doxycycline were accompanied by G1-S cell cycle arrest and DNA fragmentation in PANC-1 cells. Doxycycline consistently activated transcription of p53, p21 and Fas/FasL-cascade-related genes, while reducing the expression of Bcl-xL and Mcl-1. Doxycycline (5 μg/ml) below the cytotoxic level suppressed endogenous and paclitaxel-induced IL-8 expression. In the mouse xenograft model, doxycycline treatment was shown to suppress tumor growth by 80%. Conclusion: These data suggest that doxycycline exerts its antitumor effect by activating proapoptotic genes, inhibiting IL-8 expression, and suppressing antiapoptotic genes.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3995-4003 |
| Number of pages | 9 |
| Journal | Anticancer research |
| Volume | 29 |
| Issue number | 10 |
| State | Published - Oct 2009 |
Keywords
- Apoptosis
- Doxycycline
- Fas
- IL-8
- Pancreatic cancer
- p53
ASJC Scopus subject areas
- Oncology
- Cancer Research