Pro-senescent effect of hydrogen peroxide on cancer cells and its possible application to tumor suppression.

Mild oxidative stress is known to induce premature senescence, termed stress-induced premature senescence (SIPS), in normal human diploid cells. We investigated to determine whether mild oxidative stress would trigger SIPS in a human tumor cell line, human lung adenocarcinoma A549. The results showed that sublethal concentrations of H(2)O(2) induced SIPS in A549 cells and consequently attenuated, but did not completely eliminate, the tumorigenicity of these cells. We next investigated the reasons for this incomplete impairment of tumorigenicity in A549 cells in SIPS. The results suggested that H(2)O(2)-treated A549 cells are composed of a heterogeneous cell population: one is sensitive to H(2)O(2), and the other is resistant or undergoes reversal; the latter reverted to their original tumorigenic form. The molecular mechanisms determining the cellular fate of tumor cells in SIPS should be identified in order to make use of SIPS and oncogene-induced senescence in tumor cells as methods of tumor suppression.